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Carrieri P.B.,University of Naples Federico II | Carbone F.,University of Naples Federico II | Perna F.,University of Naples Federico II | Bruzzese D.,University of Naples Federico II | And 10 more authors.
Metabolism: Clinical and Experimental | Year: 2015

Objective We investigated the effect of glatiramer acetate (GA) on the modulation of immune cell subpopulations and serum levels of multiple immune/metabolic markers in patients with relapsing-remitting multiple sclerosis (RRMS) to understand whether the treatment with GA could induce a specific change in the immunometabolic asset of patients with RRMS. Material and methods We performed an extensive peripheral blood immunophenotyping and measured serum levels of several parameters involved in the pathogenesis of RRMS and also relevant in the pathogenesis of metabolic syndrome and obesity such as leptin, soluble leptin-receptor (sLep-R), myeloperoxidase (MPO), soluble CD40 ligand (sCD40-L), soluble tumor necrosis factor-receptor (sTNF-R), monocyte chemoattractant protein 1 (MCP-1), soluble Inter-Cellular Adhesion Molecule-1 (sICAM-1) and osteoprotegerin (OPG), in 20 naïve-to-treatment RRMS patients and 20 healthy controls. We repeated these analyses over time at 6 and 12 months after starting GA treatment. Results Our analysis showed that naïve-to-treatment RRMS patients had a lower number of CD16+CD56+ NK cells, CD19+ B cells, CD4+ T cells co-expressing the MHC class II activation marker HLA-DR (CD4+DR+) and naïve CD4+CD45RA+ T cells in basal conditions. GA treatment induced a specific and significant decrease of circulating CD19+ B cells. Naïve-to-treatment RRMS patients also showed a significantly higher number of CD4+ T cells with a memory phenotype (CD4+CD45RO+) whose peripheral frequency was not affected by GA treatment. These changes over time associated with a higher serum concentration of leptin and lower levels of MPO. GA treatment also reduced significantly the circulating levels of sCD40-L and sTNF-R overtime. Conclusions Our data suggest that the clinical outcome of GA treatment is associated with changes in immune cell subpopulations and modulation of specific immunometabolic markers. These data add substantial evidence of the immune modulating effect of GA during RRMS and could be of relevance in understanding the pathogenesis of disease and its follow-up. © 2015 Elsevier Inc. Source


Beghi E.,CNR Institute of Neuroscience | Bussone G.,CNR Institute of Neuroscience | D'Amico D.,CNR Institute of Neuroscience | Cortelli P.,University of Bologna | And 11 more authors.
Journal of Headache and Pain | Year: 2010

The objective of this paper was to assess prevalence and characteristics of anxiety and depression in migraine without aura and tension-type headache, either isolated or in combination. Although the association between headache and psychiatric disorders is undisputed, patients with migraine and/or tension-type headache have been frequently investigated in different settings and using different tests, which prevents meaningful comparisons. Psychiatric comorbidity was tested through structured interview and the MINI inventory in 158 adults with migraine without aura and in 216 persons with tension-type headache or migraine plus tension-type headache. 49 patients reported psychiatric disorders: migraine 10.9%, tension-type headache 12.8%, and migraine plus tensiontype headache 21.4%. The MINI detected a depressive episode in 59.9, 67.0, and 69.6% of cases. Values were 18.4, 19.3, and 18.4% for anxiety, 12.7, 5.5, and 14.2%, for panic disorder and 2.3, 1.1 and 9.4% (p = 0.009) for obsessive-compulsive disorder. Multivariate analysis showed panic disorder prevailing in migraine compared with the other groups (OR 2.9; 95% CI 1.2-7.0). The association was higher (OR 6.3; 95% CI 1.4-28.5) when migraine (with or without tension-type headache) was compared to pure tension-type headache. This also applied to obsessive-compulsive disorder (OR 4.8; 95% CI 1.1- 20.9) in migraine plus tension-type headache. Psychopathology of primary headache can reflect shared risk factors, pathophysiologic mechanisms, and disease burden. © Springer-Verlag 2010. Source


Chieffi S.,The Second University of Naples | Iavarone A.,Unita Operativa Complessa di Neurologia | Viggiano A.,Parthenope University of Naples | Monda M.,The Second University of Naples | Carlomagno S.,University of Trieste
Experimental Brain Research | Year: 2012

Previous studies have shown that a flanking distractor produces a spatial bias during line bisection. In the present study, we investigated whether that bias depends on perceptual or motor components. Participants were asked to bisect a horizontal line, or to reach towards a dot, with or without vision of their hand. The line and the target could be flanked by a distractor. Movement trajectories and endpoints were consistently deviated away from the location of the distractor in the bisection task, but not in the reaching task, irrespectively of whether the participants had online visual feedback from their moving hand. It is suggested that flanking distractors influence perceptual localization of the subjective mid-point during line bisection. © Springer-Verlag 2012. Source


Amenta F.,University of Camerino | Carotenuto A.,University of Camerino | Fasanaro A.M.,Unita Valutativa Alzheimer e Malattie Involutive Cerebrali | Lanari A.,Unita Operativa Complessa di Neurologia | And 4 more authors.
Giornale di Gerontologia | Year: 2010

Introduction. Acetylcholinesterase/cholinesterase inhibitors (ChE-I) are licensed for symptomatic relief of Alzheimer's disease and are also used for vascular dementia, in spite of the controversies about the clinical significance of their therapeutic effect. The present study has reviewed comparatively cardiovascular safety and efficacy of ChE-I and of the cholinergic precursor choline alphoscerate. Methods. A literature search of all randomized clinical trials and meta-analyses published from January 1999 to July 2009 was performed. Efficacy measures and adverse reactions requiring treatment discontinuation were considered. Alzheimer's disease, vascular dementia, ChE-I, and choline alphoscerate were the terms considered for the search. Results. Second generation ChE-I induce modest improvement in cognitive performances in mild and moderate Alzheimer's disease patients. In demented aged individuals treated with ChE-I, a greater risk for syncope, bradycardia, pacemaker insertion, and hip fracture, was found. The effect of choline alphoscerate on cognitive outcomes was not inferior to that of ChE-I. Treatment with choline alphoscerate was associated with a low incidence of adverse reactions and no changes in heart rate. Discussion. The risk of bradycardia in demented patients treated with ChE-I suggests that closer surveillance is warranted in patients with cardiovascular risk. In view of the good effectiveness/safety profile of choline alphoscerate, this compound may be considered as an option in older adults with dementia at risk of cardiovascular events. Source


Mancini C.,University of Turin | Vaula G.,A.O.U. San Giovanni Battista | Scalzitti L.,University of Turin | Cavalieri S.,University of Turin | And 6 more authors.
Neurogenetics | Year: 2012

Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal recessive disease characterized by early onset macrocephaly; developmental delay; motor disability in the form of progressive spasticity and ataxia; seizures; cognitive decline; and characteristic magnetic resonance imaging findings. Mutations in two genes, MLC1 (22q13.33; 75 % of patients) or HEPACAM (11q24; 20 % of patients), are associated with the disease. We describe an adult MLC patient with moderate clinical symptoms. MLC1 cDNA analysis from lymphoblasts showed a strong transcript reduction and identified a 246-bp pseudoexon containing a premature stop codon between exons 10 and 11, due to a homozygous c.895-226 T>G deep-intronic mutation. This category of mutations is often overlooked, being outside of canonically sequenced genomic regions. The mutation c.895-226 T>G has a leaky effect on splicing leaving part of the full-length transcript. Its role on splicing was confirmed using a minigene assay and an antisense morpholinated oligonucleotide targeted to the aberrant splice site in vitro, which partially abrogated the mutation effect. © 2012 Springer-Verlag. Source

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