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Search Results: 1 - 10 of 6859 matches for " Paolo Fagone "
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17 -Ethynyl-androst-5-ene-3 ,7 ,17 -triol (HE3286) Is Neuroprotective and Reduces Motor Impairment and Neuroinflammation in a Murine MPTP Model of Parkinson’s Disease
Ferdinando Nicoletti,Ingrid Philippens,Paolo Fagone,Clarence N. Ahlem,Christopher L. Reading,James M. Frincke,Dominick L. Auci
Parkinson's Disease , 2012, DOI: 10.1155/2012/969418
Abstract: 17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) is a synthetic androstenetriol in Phase II clinical development for the treatment of inflammatory diseases. HE3286 was evaluated for blood-brain barrier (BBB) permeability in mice, and efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson’s disease (PD). We found that HE3286 freely penetrated the BBB. HE3286 treatment significantly improved motor function compared to vehicle in the rotarod test (mean 58.2?sec versus 90.9?sec, ), and reduced inflammatory mediator gene expression in the brain (inducible nitric oxide synthase, 20%, ; tumor necrosis factor α, 40%, , and interleukin-1β, 33%, ) measured by reverse-transcriptase polymerase chain reaction. Brain tissue histopathology and immunohistochemistry showed that HE3286 treatment increased the numbers of tyrosine hydroxylase-positive cells by 17% compared to vehicle ( ), and decreased the numbers of damaged neurons by 38% relative to vehicle ( ). L-3,4-dihydroxyphenylalanine (L-DOPA) efficacy was not enhanced by concurrent administration of HE3286. HE3286 administration prior to MPTP did not enhance efficacy. Our data suggest a potential role for HE3286 in PD treatment, and provides incentive for further investigation. 1. Introduction PD is a neurodegenerative disorder characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) and decreased levels of dopamine in the putamen of the dorsolateral striatum. The loss of dopamine in the striatum manifests clinically as motor disabilities that include bradykinesia, resting tremor, and muscular rigidity. Diagnosis is based on motor symptoms, which become evident only after the loss of more than 50% of the SNpc DAergic neurons and 60–80% of striatal dopamine [1]. Prolonged treatment of PD with L-DOPA usually results in a dyskinesia that can be more disabling than the disease itself; therefore, there is a great need for alternative therapeutic modalities. The acute MPTP mouse model of nigrostriatal degeneration recapitulates the DAergic neuron loss seen in PD and currently represents the most commonly used toxin-induced mouse model of PD [2]. MPTP’s mechanism of toxicity is complex, and exerted through its toxic metabolite, methyl-4-phenylpyridinium (MPP+) ion, which is taken up selectively by DAergic neurons through the dopamine transporter. Inside the cell, MPP+ is a mitochondrial toxin, which induces neuronal death through several mechanisms that include oxidative stress [3], excitotoxicity [4], and
A DNA Vaccine against Chikungunya Virus Is Protective in Mice and Induces Neutralizing Antibodies in Mice and Nonhuman Primates
Karthik Mallilankaraman equal contributor,Devon J. Shedlock equal contributor,Huihui Bao,Omkar U. Kawalekar,Paolo Fagone,Aarthi A. Ramanathan,Bernadette Ferraro,Jennifer Stabenow,Paluru Vijayachari,Senthil G. Sundaram,Nagarajan Muruganandam,Gopalsamy Sarangan,Padma Srikanth,Amir S. Khan,Mark G. Lewis,J. Joseph Kim,Niranjan Y. Sardesai,Karuppiah Muthumani ,David B. Weiner
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0000928
Abstract: Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus indigenous to tropical Africa and Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, and sometimes arthritis. Relatively little is known about the antigenic targets for immunity, and no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. and Europe. Considering the potential for pandemic spread, understanding the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient and developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis and develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP) that expresses a component of the CHIKV envelope glycoprotein and used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular and humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease and support further study of envelope-based CHIKV DNA vaccines.
Inhibition of PI3K Prevents the Proliferation and Differentiation of Human Lung Fibroblasts into Myofibroblasts: The Role of Class I P110 Isoforms
Enrico Conte,Mary Fruciano,Evelina Fagone,Elisa Gili,Filippo Caraci,Maria Iemmolo,Nunzio Crimi,Carlo Vancheri
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0024663
Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disease characterized by an accumulation of fibroblasts and myofibroblasts in the alveolar wall. Even though the pathogenesis of this fatal disorder remains unclear, transforming growth factor-β (TGF-β)-induced differentiation and proliferation of myofibroblasts is recognized as a primary event. The molecular pathways involved in TGF-β signalling are generally Smad-dependent yet Smad-independent pathways, including phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), have been recently proposed. In this research we established ex-vivo cultures of human lung fibroblasts and we investigated the role of the PI3K/Akt pathway in two critical stages of the fibrotic process induced by TGF-β: fibroblast proliferation and differentiation into myofibroblasts. Here we show that the pan-inhibitor of PI3Ks LY294002 is able to abrogate the TGF-β-induced increase in cell proliferation, in α- smooth muscle actin expression and in collagen production besides inhibiting Akt phosphorylation, thus demonstrating the centrality of the PI3K/Akt pathway in lung fibroblast proliferation and differentiation. Moreover, for the first time we show that PI3K p110δ and p110γ are functionally expressed in human lung fibroblasts, in addition to the ubiquitously expressed p110α and β. Finally, results obtained with both selective inhibitors and gene knocking-down experiments demonstrate a major role of p110γ and p110α in both TGF-β-induced fibroblast proliferation and differentiation. This finding suggests that specific PI3K isoforms can be pharmacological targets in IPF.
A Field Experiment on the Recurrence of Large Waves in Wind Seas  [PDF]
Paolo Boccotti
Open Journal of Marine Science (OJMS) , 2011, DOI: 10.4236/ojms.2011.13007
Abstract: Wind generated sea waves are generally regarded as an example of pure randomness in nature. Here we give a proof that the matter is not exactly so: some identical sequences of relatively large waves were found many hours apart from one another. This finding supports the theory of quasi determinism of sea waves.
Call Auction Markets with Risk-Averse Specialists  [PDF]
Paolo Vitale
Theoretical Economics Letters (TEL) , 2012, DOI: 10.4236/tel.2012.22030
Abstract: We study a generalization of Kyle’s (1985) model to the case in which the specialist is risk-averse and does not set the transaction price according to semi-strong form efficiency. We see that Kyle’s call auction market is no longer a robust market structure, as linear Bayesian equilibria do not exist, irrespective of fundamentals, such as agents’ information, endowments and preferences. This result holds both when customers can submit only market orders and when limit orders are allowed too.
Democratic, Plutocratic and Social Weights in Price Indexes  [PDF]
Paolo Liberati
Theoretical Economics Letters (TEL) , 2012, DOI: 10.4236/tel.2012.25084
Abstract: This paper introduces social considerations into the calculation of the price index. To this purpose, recourse is made to the concept of distributional characteristic. It is shown how an aggregate price index can be expressed as a weighted average of commodity-specific prices, with weights that depend on both the aggregate share of consumption and the way in which consumption is distributed across households. The proposed index provides a complementary basis for the analysis of the impact of inflation and for the calculation of its social value.
Holographic Bound in Quantum Field Energy Density and Cosmological Constant  [PDF]
Paolo Castorina
Journal of Modern Physics (JMP) , 2013, DOI: 10.4236/jmp.2013.46110

The cosmological constant problem is reanalyzed by imposing the limitation of the number of degrees of freedom (d.o.f.) due to entropy bounds directly in the calculation of the energy density of a field theory. It is shown that if a quantum field theory has to be consistent with gravity and holography, i.e. with an upper limit of storing information in a given area, the ultraviolet momentum cut-off is not the Planck mass, Mp, as naively expected, but \"\" where Nu is the number of d.o.f. of the universe. The energy density evaluation turns out completely consistent with Bousso’s bound on the cosmological constant value. The scale \"\" , that in the “fat graviton” theory corresponds to the graviton size, originates by a self-similar rearrangement of the elementary d.o.f. at different scales that can be seen as an infrared-ultraviolet connection.

Cosmogonic Speculations: Particle Creation from Energy Conservation in the Universe Evolution  [PDF]
Paolo Christillin
Journal of Modern Physics (JMP) , 2016, DOI: 10.4236/jmp.2016.711119
Abstract: Information about the Universe from Hubble’s law is consistent with that coming from the evaluation of inertial forces, supporting the picture of a steady state expansion of a black hole Universe. Backed up also by the consideration of the black body self energy, the post big bang temperature decrease is consistent with particle creation if energy conservation applies at every scale. This process is shown to provide a gravitational repulsive force which can counterbalance gravitational attraction thus allowing the possibility of a steady non-inflationary expansion. That seems to provide an alternative coherent scheme for our picture of the Universe evolution, disposing of the cosmological term, of dark energy and of the bulk of dark matter.
Outline of a Proposal to Reform the Institutional Architecture of Money, Savings, and Credit to Reach a Financial Sustainability  [PDF]
Paolo Savona
Modern Economy (ME) , 2018, DOI: 10.4236/me.2018.96071

The scope of this paper is to examine the complications raised by technical innovations in the financial field (fintech). The conclusion of this enquire is that the current institutional architecture cannot guarantee monetary and financial sustainability as long as Governments decide to reform it using the already available instruments (cryptocurrency, blockchain, algorithms) instead of leaving them free to operate or limiting their use as they are doing. The same goes for any tentative to restate bank credibility forecasting money and financial instability starting from big data treated with traditional econometric methods.

Reactive Oxygen Species Are Required for Maintenance and Differentiation of Primary Lung Fibroblasts in Idiopathic Pulmonary Fibrosis
Marialuisa Bocchino,Savina Agnese,Evelina Fagone,Silvia Svegliati,Domenico Grieco,Carlo Vancheri,Armando Gabrielli,Alessandro Sanduzzi,Enrico V. Avvedimento
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014003
Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal illness whose pathogenesis remains poorly understood. Recent evidence suggests oxidative stress as a key player in the establishment/progression of lung fibrosis in animal models and possibly in human IPF. The aim of the present study was to characterize the cellular phenotype of fibroblasts derived from IPF patients and identify underlying molecular mechanisms.
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