Neurological Institute Foundation

Milano, Italy

Neurological Institute Foundation

Milano, Italy
SEARCH FILTERS
Time filter
Source Type

Leone M.,Neurological Institute Foundation | Vila C.,Global Medical Affairs | McGown C.,Content Ed Net
Expert Review of Neurotherapeutics | Year: 2010

In a large observational general practice study (the Standardized Study with Almotriptan in Early Treatment of Migraine [START]), 12.5 mg almotriptan administered within 1 h of pain onset and when pain was mild significantly improved pain-related outcomes, compared with later treatment or when pain was more severe. Migraine triggers at baseline and during treatment were recorded, and it was examined whether trigger factors could affect almotriptan-induced headache improvement. More than 400 patients were enrolled, and 1174 attacks were assessed. At baseline, patients reported a mean of 2.6 types of triggers related to the start of their previous migraine attacks. During the trial, a mean of 1.5 trigger factors for each attack was recorded. The most frequent trigger during the study was stress (37% of migraine attacks), with poor sleep (34%), fatigue (32%) and menses (19%) also being widely reported. Stress and fatigue and/or poor sleep were the most frequent trigger combinations. Early treatment with almotriptan improved clinical outcomes, regardless of the trigger factors involved. Similar results were observed for nonearly administration, although this was less efficacious than early intervention. An exception in the nonearly group was that migraines triggered by poor sleep had better responses than attacks in which sleep disorder was not a factor. Almotriptan maintained its efficacy irrespective of trigger factors in migraine patients treated in everyday clinical practice and, as shown in other studies, it was most effective in reducing pain-free rates when administered early, when pain was still mild. © 2010 Expert Reviews Ltd.


Lapilla M.,Neurological Institute Foundation | Gallo B.,Neurological Institute Foundation | Martinello M.,University of Verona | Procaccini C.,National Research Council Italy | And 9 more authors.
Journal of Leukocyte Biology | Year: 2011

Histamine may contribute to the pathology of MS and its animal model EAE. We explored the effects of histamine and specific HR agonists on activation and migratory capacity of myelin-autoreactive T cells. We show that histamine in vitro inhibits proliferation and IFN-γ production of mouse T cells activated against PLP139-151. These effects were mimicked by the H1R agonist HTMT and the H2R agonist dimaprit and were associated with reduced activation of ERK1/2 kinase and with increased levels of cell cycle inhibitor p27Kip-1, both involved in T cell proliferation and anergy. H1R and H2R agonists reduced spontaneous and chemokine-induced adhesion of autoreactive T cells to ICAM-1 in vitro and blocked firm adhesion of these cells in inflamed brain microcirculation in vivo. Thus histamine, through H1R and H2R, inhibits activation of myelin-autoreactive T cells and their ability to traffic through the inflamed BBB. Strategies aimed at interfering with the histamine axis might have relevance in the therapy of autoimmune disease of the CNS. © Society for Leukocyte Biology.


Piconese S.,Fondazione IRCCS Instituto Nazionale Tumori | Costanza M.,Neurological Institute Foundation | Musio S.,Neurological Institute Foundation | Tripodo C.,University of Palermo | And 7 more authors.
Laboratory Investigation | Year: 2011

Mast cell (MC)-deficient c-Kit mutant Kit W/W-v mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit W-sh/W-sh. Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG) 35-55-induced chronic EAE was exacerbated in Kit W-sh/W-sh compared with Kit +/+ mice. Kit W-sh/W-sh mice showed more inflammatory foci in the central nervous system (CNS) and increased T-cell response against myelin. To understand whether the discrepant results obtained in Kit W-sh/W-sh and in Kit W/W-v mice were because of the different immunization protocols, we induced EAE in these two strains with varying doses of MOG 35-55 and adjuvants. Although Kit W-sh/W-sh mice exhibited exacerbated EAE under all immunization protocols, Kit W/W-v mice were protected from EAE only when immunized with high, but not low, doses of antigen and adjuvants. Kit W-sh/W-sh mice reconstituted systemically, but not in the CNS, with bone marrow-derived MCs still developed exacerbated EAE, indicating that protection from disease could be exerted by MCs mainly in the CNS, and/or by other cells possibly dysregulated in Kit W-sh/W-sh mice. In summary, these data suggest to reconsider MC contribution to EAE, taking into account the variables of using different experimental models and immunization protocols. © 2011 USCAP, Inc All rights reserved.


PubMed | Neurological Institute Foundation
Type: Journal Article | Journal: Journal of leukocyte biology | Year: 2011

Histamine may contribute to the pathology of MS and its animal model EAE. We explored the effects of histamine and specific HR agonists on activation and migratory capacity of myelin-autoreactive T cells. We show that histamine in vitro inhibits proliferation and IFN- production of mouse T cells activated against PLP(139-151). These effects were mimicked by the H1R agonist HTMT and the H2R agonist dimaprit and were associated with reduced activation of ERK½ kinase and with increased levels of cell cycle inhibitor p27Kip-1, both involved in T cell proliferation and anergy. H1R and H2R agonists reduced spontaneous and chemokine-induced adhesion of autoreactive T cells to ICAM-1 in vitro and blocked firm adhesion of these cells in inflamed brain microcirculation in vivo. Thus histamine, through H1R and H2R, inhibits activation of myelin-autoreactive T cells and their ability to traffic through the inflamed BBB. Strategies aimed at interfering with the histamine axis might have relevance in the therapy of autoimmune disease of the CNS.

Loading Neurological Institute Foundation collaborators
Loading Neurological Institute Foundation collaborators