Leo A.,University of Catanzaro |
Russo E.,University of Catanzaro |
Elia M.,Oasi Institute for Research on Mental Retardation and Brain Aging IRCCS
Pharmacological Research | Year: 2016
Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remains still poor. Unfortunately, besides several advantages, these new AEDs have not satisfactorily reduced the number of refractory patients. Therefore, the need for different other therapeutic options to manage epilepsy is still a current issue. To this purpose, emphasis has been given to phytocannabinoids, which have been medicinally used since ancient time in the treatment of neurological disorders including epilepsy. In particular, the nonpsychoactive compound cannabidiol (CBD) has shown anticonvulsant properties, both in preclinical and clinical studies, with a yet not completely clarified mechanism of action. However, it should be made clear that most phytocannabinoids do not act on the endocannabinoid system as in the case of CBD. In in vivo preclinical studies, CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures, whereas restricted data exist in chronic models of epilepsy as well as in animal models of epileptogenesis. Likewise, clinical evidence seems to indicate that CBD is able to manage epilepsy both in adults and children affected by refractory seizures, with a favourable side effect profile. However, to date, clinical trials are both qualitatively and numerically limited, thus yet inconsistent. Therefore, further preclinical and clinical studies are undoubtedly needed to better evaluate the potential therapeutic profile of CBD in epilepsy, although the actually available data is promising. © 2016 Elsevier Ltd.
Pelaia G.,University of Catanzaro |
Vatrella A.,University of Salerno |
Maselli R.,University of Catanzaro
Nature Reviews Drug Discovery | Year: 2012
Recent advances in the knowledge of asthma pathobiology suggest that biological therapies that target cytokines can be potentially useful for the treatment of this complex and heterogeneous airway disease. The use of biologics in asthma has been established with the approval of the humanized monoclonal immunoglobulin E-targeted antibody omalizumab (Xolair; Genentech/Novartis) as an add-on treatment for inadequately controlled disease. Furthermore, evidence is accumulating in support of the efficacy of other biologics, such as interleukin-5 (IL-5)- and IL-13-specific drugs. Therefore, these new developments are changing the scenario of asthma therapies, especially with regard to more severe disease. The variability among patients' individual therapeutic responses highlights that it will be necessary to characterize the different asthma subtypes so that phenotype-targeted treatments based on the use of biologics can be implemented. © 2012 Macmillan Publishers Limited. All rights reserved.
Buccino G.,University of Catanzaro |
Colage I.,Pontifical University Antonianum |
Gobbi N.,Pontifical Gregorian University |
Neuroscience and Biobehavioral Reviews | Year: 2016
This work reviews key behavioural, neurophysiological and neuroimaging data on the neural substrates for processing the meaning of linguistic material, and tries to articulate the picture emerging from those findings with the notion of meaning coming from specific approaches in philosophy of language (the “internalist” view) and linguistics (words point at experiential clusters). The reviewed findings provide evidence in favour of a causal role of brain neural structures responsible for sensory, motor and even emotional experiences in attributing meaning to words expressing those experiences and, consequently, lend substantial support to an embodied and “internalist” conception of linguistic meaning. Key evidence concern verbs, nouns and adjectives with a concrete content, but the challenge that abstract domains pose to the embodied approach to language is also discussed. This work finally suggests that the most fundamental role of embodiment might be that of establishing commonalities among individual experiences of different members of a linguistic community, and that those experiences ground shared linguistic meanings. © 2016 Elsevier Ltd
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.98M | Year: 2013
The objective is to deliver a trans-European network of industrially oriented specialists fully trained in the development and application of microbioreactor (MBR) technology to support development of innovative bio-based manufacturing processes. The specialistis will be trained by leaders in the field and with state of the art equipment and methodologies. MBRs are a promising tool for screening and scale-up of fermentation and biocatalysis processes due to their low production cost, small working volumes, flexibility and their potential for information-rich experiments under well-controlled experimental conditions. In this consortium, we will further develop MBRs for chemical and biochemical screening, paying special attention to MBR parallelization and applicability for different applications. In addition, characterization of experimental uncertainty, development of reactant feeding strategies at micro-scale and coupling of microscale experimentation to automated design of experiments (DoE) will document applicability of MBRs for chemical and biochemical research. To enhance the applicability of microfluidic enzymatic reactors for organic synthesis, we will establish microfluidic chemo-biocatalytic reaction systems that enable rapid characterization of biosynthetic pathways and chemo-enzymatic conversions. This will be underpinned with immobilization methods that permit rapid and reversible binding of a range of biocatalysts and modeling that relates the kinetic data with results from larger scales. Complemented with precisely positioned fluorescence-based sensor arrays, novel nanosensor particle concepts, and integrated Raman and NIR probes, the MBRs will deliver the data-rich experimentation needed for industrial applications. Data processing and information management will be accomplished by developing CFD and mathematical modeling methods that permit prediction and interpretation of fermentation and biocatalytic processes in MBRs.
Savino R.,University of Catanzaro |
Terracciano R.,University of Catanzaro
Drug Discovery Today | Year: 2012
Mass spectrometry (MS)-profiling of human bodily fluids is a new approach for the discovery of novel disease biomarkers and, consequently, of new druggable targets. However, the complexity and the high dynamic range of biological samples make the characterization of endogenous peptides and/or proteins a challenging task. To this end, the introduction of new technologies, enabling sample pre-fractionation and/or pre-treatment before MS, could be useful. Progress in the field of nanostructured materials has provided innovative devices, particularly those based on mesoporous silica, which have proved to be successful. The ability to address new emerging material-based MS-profiling platforms will ultimately determine how deeply nanotechnology and proteomics can contribute to improve drug and/or target discovery. © 2011 Elsevier Ltd All rights reserved.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP-2008-1.1-1 | Award Amount: 4.43M | Year: 2009
Future breakthroughs in the understanding of fundamental biological processes causing major diseases are expected from the development of miniaturized probes or microscopes able to detect and identify a single or a small number of molecules. The SingleMoleculeDetection (SMD) proposal will develop a unique device able to perform simultaneously and in a dynamic way force and spectroscopic measurements. We will design and fabricate novel devices for the generation of plasmon polaritons as well as combine photonic crystals and plasmonic nanolenses. These new devices will be able to detect few/single molecules through Raman, InfraRed and Terahertz (THz) signals and in combination with Atomic Force Microscopy and Optical Tweezer force spectroscopy with a spatial resolution in the sub-10 nm for Raman and IR and sub-100 nm for the THz region. The complete characterization of single unknown molecule will be demonstrated through: i- investigations on the chemical and physical properties of membrane receptors, such as rhodopsin, odorant receptors and ionic channels; ii- identification of new molecules involved in cancer development and metastasis. The new devices will allow the acquisition of THz images and we will explore the possibilities of this new spectral region for biomedical scanning. The SMD proposal is based on an original idea of the coordinator, prof. E. di Fabrizio and will be exploited thanks to the complementary expertise present in the different sites and to a tight coordination between the various groups. The design, fabrication and testing will be performed at UMG, TASC and CBM Integration in a single instrument will be carried out at TASC, CBM, IIT Nanotec, RUB. Validation activities will be performed by all the partners taking advantage of the world leading expertise of the TUDO and the STRATH- AC in spectroscopy of natural and artificial biological systems. The SME NANOTEC and CBM will provide the commercial exploitation of the obtained results.
Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH.2011.2.4.3-4 | Award Amount: 4.32M | Year: 2012
MEDIGENE project will study genetic and environmental (G x E) determinants of the metabolic syndrome (MetS) in recent immigrants in Europe by a novel approach integrating ancestry of Mediterranean populations in epidemiology, locus refining and Genome Wide Association Studies (GWAS). West Mediterranean shores are place of pre-historical termini of population expansion from Southern Europe and North Africa. Archaeogenetic studies in Europe indicated that Y chromosome and mitochondrial DNA patterns or Ancestry Informative Markers (AIMs) revealed a close relationship between genetic and geographic distances able to locate an individual DNA within few hundred kilometers. The project will use this information in mapping the genetic basis of insulin resistance, cardiovascular and metabolic complications in immigrants (Albanians, Romanians, Turkish, Tunisians, Algerians and Morocco) in host countries France, Spain, Italy and Greece. Ancestry markers and studies on ancient DNA from Roman historical migration in Catalonia will help to give a better picture of the genetic landscape of Europe and North Africa. Genes for MetS will be studied in existing samples from host and home countries by GWAS, locus refining by next-generation sequencing and haplotype mapping. Informative filtered SNPs will be then used in epidemiology and novel DNA samples to reveal G x E interactions and specificities of the pathogenesis of MetS. Genetic findings will be replicated in home countries (Anatolia and North Africa) in the goal to develop markers ethnic specific and significant at a clinical scale. Major impact is expected from dissemination of our findings to prevent the occurrence of MetS and obesity in children and adolescents or in descendants of modern immigration, understanding variability clinical manifestations of MetS in the context of malnutrition and from the novel approach of GWAS strategies by ameliorating the association signal and bursting R&D activities of SMEs.
Pelaia G.,University of Catanzaro
Pharmacology | Year: 2014
Bronchodilators are the cornerstone of the treatment of chronic obstructive pulmonary disease (COPD). In particular, the most commonly used drugs are inhaled long-acting agents, including long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic receptor antagonists (LAMAs). The combination of a LABA with a LAMA, i.e. of molecules characterized by different mechanisms of action, results in a synergistic enhancement of their clinical and functional effects. Therefore, this combined treatment can be implemented in a number of cases in which disease control is not adequately achieved by a single active agent such as a LABA or a LAMA. Several LABA/LAMA fixed-dose combinations, mainly made up of newly developed compounds, are currently in advanced phases of experimental evaluation. Within such a context, the aim of this review is to outline the pharmacological basis of dual bronchodilation as well as to discuss the results of the main trials carried out using the drug combination consisting of indacaterol and glycopyrronium, a LABA and a LAMA recently introduced in the treatment of COPD. © 2014 S. Karger AG, Basel Copyright © 2014, S. Karger AG. All rights reserved.
Pietropaolo A.,University of Catanzaro |
Nakano T.,Hokkaido University
Journal of the American Chemical Society | Year: 2013
Helical polymers with switchable screw sense are versatile frameworks for chiral functional materials. In this work, we reconstructed the free energy landscape of helical poly(2,7-bis(4-tert-butylphenyl)fluoren-9-yl acrylate) [poly(BBPFA)], as its racemization is selectively driven by light without any rearrangement of chemical bonds. The chirality inversion was enforced by atomistic free energy simulations using chirality indices as reaction coordinates. The free energy landscape reproduced the experimental electronic circular dichroism spectra. We propose that the chirality inversion of poly(BBPFA) proceeds from a left-handed 31 helix via multistate free energy pathways to reach the right-handed 31 helix. The inversion is triggered by the rotation of biphenyl units with an activation barrier of 38 kcal/mol. To the best of our knowledge, this is the first report on the chiral inversion mechanism of a helical polymer determined in a quantitative way in the framework of atomistic free energy simulations. © 2013 American Chemical Society.
Torella D.,University of Catanzaro
Journal of the American Heart Association | Year: 2014
Diabetes mellitus (DM) has multifactorial detrimental effects on myocardial tissue. Recently, carbonic anhydrases (CAs) have been shown to play a major role in diabetic microangiopathy but their role in the diabetic cardiomyopathy is still unknown. We obtained left ventricular samples from patients with DM type 2 (DM-T2) and nondiabetic (NDM) patients with postinfarct heart failure who were undergoing surgical coronary revascularization. Myocardial levels of CA-I and CA-II were 6- and 11-fold higher, respectively, in DM-T2 versus NDM patients. Elevated CA-I expression was mainly localized in the cardiac interstitium and endothelial cells. CA-I induced by high glucose levels hampers endothelial cell permeability and determines endothelial cell apoptosis in vitro. Accordingly, capillary density was significantly lower in the DM-T2 myocardial samples (mean±SE=2152±146 versus 4545±211/mm(2)). On the other hand, CA-II was mainly upregulated in cardiomyocytes. The latter was associated with sodium-hydrogen exchanger-1 hyperphosphorylation, exaggerated myocyte hypertrophy (cross-sectional area 565±34 versus 412±27 μm(2)), and apoptotic death (830±54 versus 470±34 per 10(6) myocytes) in DM-T2 versus NDM patients. CA-II is activated by high glucose levels and directly induces cardiomyocyte hypertrophy and death in vitro, which are prevented by sodium-hydrogen exchanger-1 inhibition. CA-II was shown to be a direct target for repression by microRNA-23b, which was downregulated in myocardial samples from DM-T2 patients. MicroRNA-23b is regulated by p38 mitogen-activated protein kinase, and it modulates high-glucose CA-II-dependent effects on cardiomyocyte survival in vitro. Myocardial CA activation is significantly elevated in human diabetic ischemic cardiomyopathy. These data may open new avenues for targeted treatment of diabetic heart failure.