Fondazione SDN

Napoli, Italy

Fondazione SDN

Napoli, Italy
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Palomba R.,Houston Methodist Research Institute | Parodi A.,Houston Methodist Research Institute | Evangelopoulos M.,Houston Methodist Research Institute | Acciardo S.,Houston Methodist Research Institute | And 10 more authors.
Scientific Reports | Year: 2016

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature. © The Author(s) 2016.

Picascia A.,Reference Pathology Laboratory | Grimaldi V.,Reference Pathology Laboratory | Zullo A.,University of Sannio | Infante T.,Fondazione SDN | And 6 more authors.
Experimental and Clinical Transplantation | Year: 2012

Sensitized candidates for heart transplant usually end up on a long waiting list and have an increased risk of rejection, graft loss, and incidence of cardiac allograft vasculopathy. An increasing number of studies have demonstrated the negative effect of preformed and posttransplant antibodies on graft survival. Thus, in sensitized patients, the combination of new, appropriate, desensitization protocols, and monitoring of posttransplant development of donor-specific antibodies may improve short-term and long-term outcomes. Introduction of more-sensitive and more-specific techniques for antibody detection provides a valid tool for assessing the degree of pretransplant HLA histocompatibility, and, therefore, predicting the results of crossmatch in sensitized patients, which are difficult to transplant. Currently, there are no accurate and standard methods to determine the functional characteristics of antibodies detected by solid-phase assay and, therefore, to predict their clinical relevance. Therefore, the future of heart transplantation requires a better understanding of tissue typing techniques and the effect of anti-HLA antibodies on clinical outcome to prevent discrimination against sensitized patients at the time of organ allocation. © Başkent University 2012 Printed in Turkey. All Rights Reserved.

Napoli C.,The Second University of Naples | Paolisso G.,The Second University of Naples | Casamassimi A.,The Second University of Naples | Al-Omran M.,King Saud University | And 4 more authors.
Journal of the American College of Cardiology | Year: 2013

Nitric oxide (NO) has been suggested to be a pathophysiological modulator of cell proliferation, cell cycle arrest, and apoptosis. In this context, NO can exert opposite effects under diverse conditions. Indeed, several studies have indicated that low relative concentrations of NO seem to favor cell proliferation and antiapoptotic responses and higher levels of NO favor pathways inducing cell cycle arrest, mitochondria respiration, senescence, or apoptosis. Here we report the effects of NO on both promotion and inhibition of cell proliferation, in particular in regard to cardiovascular disease, diabetes, and stem cells. Moreover, we focus on molecular mechanisms of action involved in the control of cell cycle progression, which include both cyclic guanosine monophosphate-dependent and -independent pathways. This growing field may lead to broad and novel targeted therapies against cardiovascular diseases, especially concomitant type 2 diabetes, as well as novel bioimaging NO-based diagnostic tools. © 2013 American College of Cardiology Foundation.

Longo F.,Bocconi University | Salvatore D.,Fondazione SDN | Tasselli S.,Bocconi University | Tasselli S.,University of Cambridge
International Journal of Health Planning and Management | Year: 2011

The nature of the local health authorities (LHAs) in the Italian National Health Service has been deeply reformed during the 1990s by new public management (NPM) reforms that introduced decentralization, quasi-market and managerialism. These reforms implied that the main role of LHA is to govern the production of health services in their area (steer) rather than to only directly produce services (row). After more than 15years from these reforms of Italian healthcare, we describe how much the steering versus rowing dichotomy made an impact on LHA activity, through an analysis of the management control systems they set up for themselves and the subsequent qualitative analysis of the opinions that a diverse group of managers expressed during 8days of group discussion. Results show that managers of Italian LHAs, when only a small part of services is produced, tend to perceive their steering role as impossible to play and focus on production, leaving therefore ungoverned a significant part of the services offered to residents. NPM, therefore, was able to influence the reform of Italian healthcare but, as suggested by a postmodernist interpretation, left managers with a rhetoric change based on inconsistent assumptions instead of actionable ideas to manage the change process. © 2011 John Wiley & Sons, Ltd.

Picardi M.,University of Naples Federico II | Soricelli A.,Fondazione SDN | Grimaldi F.,University of Naples Federico II | Nicolai E.,Fondazione SDN | And 2 more authors.
Annals of Oncology | Year: 2011

Background: Spleen and liver assessment for occult involvement of Hodgkin's lymphoma (HL) challenges current staging procedures. Patients and methods: We prospectively evaluated event-free survival (EFS) in 103 HL patients staged with fused 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/contrast-enhanced computed tomography (CT) to identify those at greatest risk for abdominal relapse. The EFS of this series was compared with that of a historical cohort of 100 HL patients staged with separate FDG-PET and diagnostic CT acquisitions. Results: Thirty-one of the 103 patients staged with FDG-PET/contrast-enhanced CT were found to have spleen involvement and 10 patients liver involvement, whereas 14 of the 100 patients staged with separate procedures were found to have spleen involvement and 3 patients liver involvement. There were significantly more intensive treatments (six courses of anthracycline-containing chemotherapy and spleen radiation) in the fused PET/CT group than in the historical cohort (P ≤ 0.04). At a median follow-up of 27 months, five events occurred in the fused PET/CT group (HL relapse, 4 patients; carcinoma, 1 patient) and 19 events in the historical cohort (HL relapse, 18 patients; acute promyelocytic leukemia, 1 patient). Ten of the 18 relapses in the historical cohort were localized in the spleen and/or liver area. None of the four relapses in the fused PET/CT group was localized below the diaphragm. Thus, FDG-PET/contrast-enhanced CT-guided treatment resulted in a 95% EFS, whereas separate FDG-PET and diagnostic CT-guided treatment resulted in an 81% EFS (P = 0.002). Conclusion: FDG-PET/contrast-enhanced CT is an accurate frontline single imaging diagnostic tool enabling effective tailored treatment in HL patients. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Quintavalle C.,University of Naples Federico II | Incoronato M.,Fondazione SDN | Puca L.,University of Naples Federico II | Acunzo M.,University of Naples Federico II | And 8 more authors.
Cell Death and Differentiation | Year: 2010

Akt is a serine-threonine kinase that has an important role in transducing survival signals. Akt also regulates a number of proteins involved in the apoptotic process. To find new Akt interactors, we performed a two-hybrid screening in yeast using full-length Akt cDNA as bait and a human cDNA heart library as prey. Among 200 clones obtained, two of them were identified as coding for the c-FLIP L protein. c-FLIP L is an endogenous inhibitor of death receptor-induced apoptosis through the caspase-8 pathway. Using co-immunoprecipitation experiments of either transfected or endogenous proteins, we confirmed the interaction between Akt and c-FLIP L. Furthermore, we observed that c-FLIP L overexpression interferes with Gsk3-Β phosphorylation levels. Moreover, through its effects on Gsk3Β, c-FLIP L overexpression in cancer cells induced resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This effect was mediated by the regulation of p27 Kip1 and caspase-3 expression. These results indicate the existence of a new mechanism of resistance to TRAIL in cancer cells, and unexpected functions of c-FLIP L. © 2010 Macmillan Publishers Limited All rights reserved.

Quintavalle C.,CNR Institute of Neuroscience | Donnarumma E.,Fondazione SDN | Fiore D.,CNR Institute of Neuroscience | Briguori C.,Laboratory of Interventional Cardiology | Condorelli G.,CNR Institute of Neuroscience
Current Opinion in Cardiology | Year: 2013

Purpose of Review: Contrast-induced acute kidney injury (CI-AKI) accounts for approximately 10% of all causes of hospital-acquired renal failure, causes a prolonged in-hospital stay, and represents a powerful predictor of poor early and late outcome. Here, we highlight endpoints used to assess major strategies to prevent CI-AKI. Recent Findings: A general consensus exists on the beneficial prophylactic effect of hydration. This seems to act by increasing urine flow rate and, thereby, by limiting the time of contact between the contrast media and the epithelial tubular cells. On the contrary, both observational trials and randomized studies are often controversial in their conclusions on the efficacy of several drugs tested to prevent CI-AKI. Compounds evaluated include diuretics (furosemide), antioxidants (i.e., N-acetylcysteine and statins), and vasodilators (i.e., calcium antagonists, dopamine, and fenoldopam). Due to the negative and/or controversial clinical results, none of these drugs has been currently recommended to prevent CI-AKI. CONCLUSION: More reliable markers of acute kidney injury and new prophylactic strategies are warranted to prevent the incidence of CI-AKI. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Briguori C.,Laboratory of Interventional Cardiology | Quintavalle C.,CNR Institute of Neuroscience | De Micco F.,IRCCS Multimedica | Condorelli G.,Fondazione SDN
Archives of Toxicology | Year: 2011

Contrast-induced acute kidney injury (CI-AKI) accounts for approximately 10% of all causes of hospital-acquired renal failure, causes a prolonged in-hospital stay, and represents a powerful predictor of poor early and late outcome. N-acetylcysteine (NAC) is a thiol compound classically known as a mucolytic agent, which is a potent antioxidant that scavenges a wide variety of oxygen-derived-free-radicals and may be capable of preventing acute kidney injury. In the present study, we will review (1) the pathophysiology of the CI-AKI and (2) the experimental and clinical data on the effects of NAC in preventing CI-AKI. © 2010 Springer-Verlag.

Picascia A.,Regional Reference Laboratory of Transplant Immunology LIT | Infante T.,Fondazione SDN | Napoli C.,Regional Reference Laboratory of Transplant Immunology LIT | Napoli C.,Excellence Research Center on Cardiovascular Diseases
Clinical and Experimental Nephrology | Year: 2012

Preformed anti-human leukocyte antigen (HLA) antibodies have a negative effect on kidney transplantation outcome with an increased rejection rate and reduction in survival. Posttransplantation production of donor-specific anti-HLA antibodies is indicative of an active immune response and risk of transplantation rejection. For many years the primary technique for anti-HLA antibody detection was complement-dependent cytotoxicity (CDC), which has been integrated by solid-phase assays as HLA antigen-coated bead methods (Luminex). This new technological approach has allowed identification of anti-HLA antibodies, not detectable using conventional CDC method, in patients awaiting kidney transplantation. Moreover, use of Luminex technology has enabled better definition of acceptable or unacceptable antigens favoring transplantation in highly immunized patients. However, there are still many unresolved issues, including the clinical relevance of antibodies detected with this system. © Japanese Society of Nephrology 2012.

Napoli C.,The Second University of Naples | Infante T.,Fondazione SDN | Casamassimi A.,The Second University of Naples
Cardiovascular Research | Year: 2011

Several studies indicate that impaired foetal growth, and in utero exposure to risk factors, especially maternal hypercholesterolaemia, may be relevant for the early onset of cardiovascular damage. The exact molecular mechanisms of such foetal programming are still unclear. Epigenetics may represent one of the possible scientific explanations of the impact of such intrauterine risk factors for the subsequent development of cardiovascular disease (CVD) during adulthood. Translational studies support this hypothesis; however, a direct causality in humans has not been ascertained. This hypothesis could be investigated in primates and in human post-mortem foetal arteries. Importantly, some studies also suggest the transgenerational transmission of epigenetic risk. The recently launched International Human Epigenome Consortium and the NIH Roadmap Epigenomics Mapping Consortium will provide the rationale for a useful clinical scenario for primary prevention and therapy of CVD. Despite the heritable nature of epigenetic modification, the clinically relevant information shows that it could be reversible through therapeutic approaches, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, and commonly used drugs such as statins. © 2011 The Author.

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