Latest PUBLICATIONS

  • Astrocyte-neuron interplay in maladaptive plasticity.
    Publication Date: 01/05/2014, on Neuroscience and biobehavioral reviews
    by Papa M, De Luca C, Petta F, Alberghina L, Cirillo G
    DOI: 10.1016/j.neubiorev.2014.01.010

    The complexity of neuronal networks cannot only be explained by neuronal activity so neurobiological research in the last decade has focused on different components of the central nervous system: the glia. Glial cells are fundamental elements for development and maintenance of physiological brain work. New data confirm that glia significantly influences neuronal communication through specific molecules, named "gliotransmitters", and their related receptors. This new approach to the traditional model of the way synapses work is also supported by changes occurring in pathological conditions, such as neurodegenerative diseases or toxic/traumatic injury to nervous system. Experimental models have revealed that glial cells are the starting point of damage progression that subsequently involves neurons. The "bedside to bench" approach has demonstrated that clinical phenotypes are strictly related to neuronal death, however it is conceivable that the disease begins earlier, years before clinical onset. This temporal gap is necessary to determine complex changes in the neuro-glial network organization and produce a "maladaptive plasticity". We review the function of glial cells in health and disease, pointing the putative mechanisms of maladaptive plasticity, suggesting that glial cells may represent a fascinating therapeutic target to prevent irreversible neuronal cell death.

  • Bovine seminal ribonuclease triggers Beclin1-mediated autophagic cell death in pancreatic cancer cells.
    Publication Date: 01/05/2014, on Biochimica et biophysica acta
    by Fiorini C, Gotte G, Donnarumma F, Picone D, Donadelli M
    DOI: 10.1016/j.bbamcr.2014.01.025

    Among the large number of variants belonging to the pancreatic-type secretory ribonuclease (RNase) superfamily, bovine pancreatic ribonuclease (RNase A) is the proto-type and bovine seminal RNase (BS-RNase) represents the unique natively dimeric member. In the present manuscript, we evaluate the anti-tumoral property of these RNases in pancreatic adenocarcinoma cell lines and in nontumorigenic cells as normal control. We demonstrate that BS-RNase stimulates a strong anti-proliferative and pro-apoptotic effect in cancer cells, while RNase A is largely ineffective. Notably, we reveal for the first time that BS-RNase triggers Beclin1-mediated autophagic cancer cell death, providing evidences that high proliferation rate of cancer cells may render them more susceptible to autophagy by BS-RNase treatment. Notably, to improve the autophagic response of cancer cells to BS-RNase we used two different strategies: the more basic (as compared to WT enzyme) G38K mutant of BS-RNase, known to interact more strongly than wt with the acidic membrane of cancer cells, or BS-RNase oligomerization (tetramerization or formation of larger oligomers). Both mutant BS-RNase and BS-RNase oligomers potentiated autophagic cell death as compared to WT native dimer of BS-RNase, while the various RNase A oligomers remained completely ineffective. Altogether, our results shed more light on the mechanisms lying at the basis of BS-RNase antiproliferative effect in cancer cells, and support its potential use to develop new anti-cancer strategies.

  • Diagnostic accuracy of short-time inversion recovery sequence in Graves' Ophthalmopathy before and after prednisone treatment.
    Publication Date: 01/05/2014, on Neuroradiology
    by Tortora F, Prudente M, Cirillo M, Elefante A, Belfiore MP, Romano F, Cappabianca S, Carella C, Cirillo S
    DOI: 10.1007/s00234-014-1332-4

    In Graves' Ophthalmopathy, it is important to distinguish active inflammatory phase, responsive to immunosuppressive treatment, from fibrotic unresponsive inactive one. The purpose of this study is, first, to identify the relevant orbital magnetic resonance imaging signal intensities before treatment, so to classify patients according to their clinical activity score (CAS), discriminating inactive (CAS < 3) from active Graves' Ophthalmopathy (GO) (CAS > 3) subjects and, second, to follow post-steroid treatment disease.

  • Interleukin 28B rs12979860 single-nucleotide polymorphism predicts spontaneous clearance of hepatitis C virus in children.
    Publication Date: 01/05/2014, on Journal of pediatric gastroenterology and nutrition
    by Indolfi G, Mangone G, Calvo PL, Bartolini E, Regoli M, Serranti D, Calitri C, Tovo PA, de Martino M, Azzari C, Resti M
    DOI: 10.1097/MPG.0000000000000275

    Recent genome-wide association studies performed in adults correlated single-nucleotide polymorphisms (SNPs rs12979860 and rs8099917) located on chromosome 19, upstream of the interleukin 28B gene, with spontaneous clearance of hepatitis C virus and with response to treatment with paginated interferon and ribavirin. The aim of the present collaborative study was to evaluate the rs12979860 SNP in a large cohort of Italian children with perinatal acquisition of hepatitis C.

  • Sleep disorders in spinal and bulbar muscular atrophy (Kennedy's disease): a controlled polysomnographic and self-reported questionnaires study.
    Publication Date: 01/05/2014, on Journal of neurology
    by Romigi A, Liguori C, Placidi F, Albanese M, Izzi F, Uasone E, Terracciano C, Marciani MG, Mercuri NB, Ludovisi R, Massa R
    DOI: 10.1007/s00415-014-7293-z

    No data are available regarding the occurrence of sleep disorders in spinal and bulbar muscular atrophy (SBMA). We investigated the sleep-wake cycle in SBMA patients compared with healthy subjects. Nine SBMA outpatients and nine age-matched and sex-matched healthy controls were evaluated. Subjective quality of sleep was assessed by means of the Pittsburgh Sleep Quality Index (PSQI). The Epworth Sleepiness Scale was used in order to evaluate excessive daytime sleepiness. All participants underwent a 48-h polysomnography followed by the multiple sleep latency test. Time in bed, total sleep time and sleep efficiency were significantly lower in SBMA than controls. Furthermore, the apnea-hypopnea index (AHI) was significantly higher in SBMA than controls. Obstructive sleep apnea (OSA: AHI >5/h) was evident in 6/9 patients (66.6 %). REM sleep without atonia was evident in three patients also affected by OSA and higher AHI in REM; 2/9 (22.2 %) SBMA patients showed periodic limb movements in sleep. The global PSQI score was higher in SBMA versus controls. Sleep quality in SBMA is poorer than in controls. OSA is the most common sleep disorder in SBMA. The sleep impairment could be induced both by OSA or/and the neurodegenerative processes involving crucial areas regulating the sleep-wake cycle.

  • Immediate versus delayed integrated point-of-care-ultrasonography to manage acute dyspnea in the emergency department.
    Publication Date: 27/04/2014, on Critical ultrasound journal
    by Pirozzi C, Numis FG, Pagano A, Melillo P, Copetti R, Schiraldi F
    DOI: 10.1186/2036-7902-6-5

    Dyspnea is one of the most frequent complaints in the Emergency Department. Thoracic ultrasound should help to differentiate cardiogenic from non-cardiogenic causes of dyspnea. We evaluated whether the diagnostic accuracy can be improved by adding a point-of-care-ultrasonography (POC-US) to routine exams and if an early use of this technique produces any advantage.

  • Astrogliosis as a therapeutic target for neurodegenerative diseases.
    Publication Date: 17/04/2014, on Neuroscience letters
    by Colangelo AM, Alberghina L, Papa M
    DOI: 10.1016/j.neulet.2014.01.014

    Chronic neurodegenerative diseases represent major unmet needs for therapeutic interventions. Recently, the neurocentric view of brain function and disease has been challenged by a great number of evidence supporting the physiopathological potential of neuroglia. Astrocytes, in particular, play a pivotal role in brain homeostasis as they actively participate in neuronal metabolism, synaptic plasticity and neuroprotection. Furthermore, they are intrinsic components of brain responses to toxic and traumatic insults through complex processes involving several molecular and functional alterations that may lead to disruption of brain homeostasis and connectivity. This review provides a brief overview of current knowledge of astrocyte functions in the brain, and focuses on some glial-specific pathways involved in astrocytic dysfunction that might be effective therapeutic targets for clinical management of neurodegenerative disorders.

  • Comorbidities and crash involvement among younger and older drivers.
    Publication Date: 10/04/2014, on PloS one
    by Papa M, Boccardi V, Prestano R, Angellotti E, Desiderio M, Marano L, Rizzo MR, Paolisso G
    DOI: 10.1371/journal.pone.0094564

    Previous studies identified comorbidities as predictors of older driver performance and driving pattern, while the direct impact of comorbidities on road crash risk in elderly drivers is still unknown. The present study is a cross-sectional aimed at investigating the association between levels of comorbidity and crash involvement in adult and elderly drivers. 327 drivers were stratified according to age range in two groups: elderly drivers (age ≥70 years old, referred as older) and adult drivers (age <70 years old, referred as younger). Driving information was obtained through a driving questionnaire. Distance traveled was categorized into low, medium and high on the basis of kilometers driven in a year. CIRS-illness severity (IS) and CIRS-comorbidity indices (CI) in all populations were calculated. Older drivers had a significantly higher crash involvements rate (p = .045) compared with the younger group based on the number of licensed drivers. Dividing comorbidity indices into tertiles among all licensed subjects, the number of current drivers significantly decreased (p<.0001) with increasing level of comorbidity. The number of current drivers among older subjects significantly decreased with increasing comorbidity level (p = .026) while no difference among younger group was found (p = .462). Among younger drivers with increasing comorbidity level, the number of road accidents significantly increased (p = .048) and the logistic regression analysis showed that comorbidity level significantly associated with crash involvement independent of gender and driving exposure. Older subjects with high level of comorbidity are able to self-regulate driving while comorbidity burden represents a significant risk factor for crash involvements among younger drivers.

  • Ranolazine protects from doxorubicin-induced oxidative stress and cardiac dysfunction.
    Publication Date: 01/04/2014, on European journal of heart failure
    by Tocchetti CG, Carpi A, Coppola C, Quintavalle C, Rea D, Campesan M, Arcari A, Piscopo G, Cipresso C, Monti MG, De Lorenzo C, Arra C, Condorelli G, Di Lisa F, Maurea N
    DOI: 10.1002/ejhf.50

    Doxorubicin is widely used against cancer; however, it can produce heart failure (HF). Among other hallmarks, oxidative stress is a major contributor to HF pathophysiology. The late INa inhibitor ranolazine has proven effective in treating experimental HF. Since elevated [Na+]i is present in failing myocytes, and has been recently linked with reactive oxygen species (ROS) production, our aim was to assess whether ranolazine prevents doxorubicin-induced cardiotoxicity, and whether blunted oxidative stress is a mechanism accounting for such protection.

  • Clinical and neuropsychological long-term outcomes after late recovery of responsiveness: a case series.
    Publication Date: 01/04/2014, on Archives of physical medicine and rehabilitation
    by Estraneo A, Moretta P, Loreto V, Santoro L, Trojano L
    DOI: 10.1016/j.apmr.2013.11.004

    To report clinical conditions and neuropsychological functioning of patients with late recovery of responsiveness at least 5 years after injury.

  • Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.
    Publication Date: 01/04/2014, on International journal of immunopathology and pharmacology
    by Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, Lus G, Ardito B, Farina D, Rossi M, Di Carmine C, Altobelli E, Maccarone B, Casalena A, De Luca G, Travaglini D, Di Ioia M, Di Tommaso V, Fantozzi R, Ruggieri S, Provinciali L, De Riso S, Mundi C, Fuiani A, Galgani S, Ruggieri S, Maniscalco GT, Giuliani G, Cartechini E, Petretta V, Fratta M, Alfieri G, Gatto M, Carolei A,
    DOI: 10.1177/039463201402700201

    We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68&#x0025;; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93&#x0025;; the proportion of patients free from combined clinical activity was 65&#x0025;; the proportion of patients free from MRI activity was 77&#x0025;; and the proportion of patients free from any disease activity was 53&#x0025;. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

  • Coexistence of cavernous hemangioma and other vascular malformations of the orbit. A report of three cases.
    Publication Date: 01/04/2014, on The neuroradiology journal
    by Strianese D, Napoli M, Russo C, D'Errico A, Scotti N, Puoti G, Bonavolontà G, Tranfa F, Briganti F
    DOI: 10.15274/NRJ-2014-10016

    Coexistence of orbital cavernous hemangioma and other vascular malformations is unusual and few cases have been reported. We describe the clinical and radiological features of three cases of orbital cavernous hemangiomas associated with other vascular malformations, selected reviewing a series of 181 cases of cavernous hemangiomas. All patients were males (age ranging from 43 to 67 years) without vascular systemic disorders and/or a clinical syndrome. They experienced slow progressive exophthalmos. One of them developed acute pulsatile proptosis (case 2), while another experienced slow progressive diplopia (case 3). In one case vascular lesions were bilateral (case 3) and in two patients two different lesions coexisted in the same orbit (cases 1 and 2). All patients underwent surgical excision, which was partial in two cases. Two patients had cavernous hemangiomas in association with a venous malformation (a varix in case 1 and a lymphangioma in case 2), while in the other ones (case 3) cavernous hemangioma was associated with a low-flow arteriovenous malformation. No patient denied visual impairment postoperatively. Few cases of orbital cavernous hemangiomas coexisting with other vascular malformations have been reported in the literature. This entity seems to be an association of different variants of orbital vascular malformations, presenting with a wide spectrum of clinical forms and probably with the same pathogenesis.

  • Efficient gene delivery to the cone-enriched pig retina by dual AAV vectors.
    Publication Date: 01/04/2014, on Gene therapy
    by Colella P, Trapani I, Cesi G, Sommella A, Manfredi A, Puppo A, Iodice C, Rossi S, Simonelli F, Giunti M, Bacci ML, Auricchio A
    DOI: 10.1038/gt.2014.8

    Gene therapy with adeno-associated viral (AAV) vectors is limited by AAV cargo capacity that prevents their application to the inherited retinal diseases (IRDs), such as Stargardt disease (STGD) or Usher syndrome type IB (USH1B), which are due to mutations in genes larger than 5 kb. Trans-splicing or hybrid dual AAV vectors have been successfully exploited to reconstitute large gene expression in the mouse retina. Here, we tested them in the large cone-enriched pig retina that closely mimics the human retina. We found that dual AAV trans-splicing and hybrid vectors transduce pig photoreceptors, the major cell targets for treatment of IRDs, to levels that were about two- to threefold lower than those obtained with a single AAV vector of normal size. This efficiency is significantly higher than that in mice, and is potentially due to the high levels of dual AAV co-transduction we observe in pigs. We also show that subretinal delivery in pigs of dual AAV trans-splicing and hybrid vectors successfully reconstitute, albeit at variable levels, the expression of the large genes ABCA4 and MYO7A mutated in STGD and USH1B, respectively. Our data support the potential of dual AAV vectors for large gene reconstitution in the cone-enriched pig retina that is a relevant preclinical model.

  • N-methylated derivatives of tyramine in citrus genus plants: identification of N,N,N-trimethyltyramine (candicine).
    Publication Date: 26/03/2014, on Journal of agricultural and food chemistry
    by Servillo L, Giovane A, D'Onofrio N, Casale R, Cautela D, Ferrari G, Balestrieri ML, Castaldo D
    DOI: 10.1021/jf5001698

    The distribution of tyramine and its methylated derivatives, N-methyltyramine and N,N-dimethyltyramine, was investigated in tissue parts (leaves and fruits) of several plants of Citrus genus by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). In the course of our study we discovered the occurrence of N,N,N-trimethyltyramine in all citrus plants examined. This quaternary ammonium compound, known to act in animals as a neurotoxin, was recognized and characterized by mass spectrometric analysis. The substance, never described before in the Citrus genus, is also known as candicine or maltoxin. Results indicate that N,N,N-trimethyltyramine is consistently expressed in leaves of clementine, bitter orange, and lemon. Conversely, low levels were found in the leaves of orange, mandarin, chinotto (Citrus myrtifolia), bergamot, citron, and pomelo. In the edible part of the fruits, N,N,N-trimethyltyramine was found at trace levels.

  • Bioavailability of encapsulated resveratrol into nanoemulsion-based delivery systems.
    Publication Date: 15/03/2014, on Food chemistry
    by Sessa M, Balestrieri ML, Ferrari G, Servillo L, Castaldo D, D'Onofrio N, Donsì F, Tsao R
    DOI: 10.1016/j.foodchem.2013.09.088

    Different O/W nanoemulsion-based delivery systems were developed in order to optimize the bioavailability of encapsulated resveratrol for potential oral administration. Blank formulations without resveratrol had no negative effect on cell viability or the cytoskeleton structure of Caco-2 cells (XTT viability assay and confocal microscopy). All nanoemulsions were then evaluated based on permeability tests on Caco-2 cells. As a result, the most efficient formulations were lecithin-based nanoemulsions which were able to transport resveratrol through cell monolayers in characteristically shorter times (1-6h) than those required for their metabolization (3-12h), allowing for better preservation of the integrity of the emulsion droplets, thus better protecting the resveratrol molecule. Fluorescence spectroscopy studies confirmed that resveratrol was encapsulated in the inner core of the nanoemulsions, which provides protection against chemical degradation. Furthermore, the developed systems also demonstrated the capability of nanoemulsions in sustained release of resveratrol from dialysis bags compared to the unencapsulated compound.