1,720,988 research outputs found
Metalloproteinases and their inhibitors as therapeutic targets for multiple sclerosis: current evidence and future perspectives
Full text linkThe treatment of multiple sclerosis (MS) has seen important changes in the last two decades with the introduction of several drugs able to modify the evolution of this disease. Current MS therapies primarily target the peripheral immune response, although it has been suggested that their ef cacy could be in part the result of the bene cial effect on other non- speci c targets, such as matrix metalloproteinases (MMPs). Numerous experimental studies have suggested that MMPs may be involved in MS pathogenesis by contributing to blood–brain barrier disruption, migration of leukocytes into the central nervous system, demyelination and axonal damage. Therefore, MMPs have been considered important therapeutic targets in the course of MS. In this respect, different attempts have been made to develop synthetic, low-molecular-weight inhibitors of MMPs for the potential treatment of diseases in which MMPs play a major role. However, technical dif culties, side effects and reduced patient compliance because of parenteral administration have greatly limited the development in the clinical practice of speci c anti-MMP drugs. By contrast, interesting results have been obtained with compounds that are already used in the clinical practice, such as MS drugs and natural compounds with anti-in ammatory and antioxidant activity. Here, we discuss the evidence and potential mechanisms for altered MMP function in MS. Furthermore, we outline the possible medical implications for the use of compounds that target MMP activity and we propose that together with anti-MS drugs, other compounds with anti-in ammatory and antioxidant properties, such as natural ω3 fatty acids, polyphenols and tetracyclines, which inhibit MMP functions, might represent potential therapeutic approaches to mitigate MMP-related damage during MS
Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation
Full text linkIsothiocyanates (ITCs), present as glucosinolate precursors in cruciferous vegetables, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of three different ITCs on ROS production and on the expression of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of various neurological diseases. Primary cultures of rat astrocytes were activated by LPS and simultaneously treated with different doses of Allyl isothiocyanate (AITC), 2-Phenethyl isothiocyanate (PEITC) and 2-Sulforaphane (SFN). Results showed that SFN and PEITC were able to counteract ROS production induced by H2O2. The zymographic analysis of cell culture supernatants evidenced that PEITC and SFN were the most effective inhibitors of MMP-9, whereas, only SFN significantly inhibited MMP-2 activity. PCR analysis showed that all the ITCs used significantly inhibited both MMP-2 and MMP-9 expression. The investigation on the mitogen-activated protein kinase (MAPK) signaling pathway demonstrated that ITCs modulate MMP transcription by inhibition of extracellular-regulated protein kinase (ERK) activity. Results of this study suggest that ITCs could be promising nutraceutical agents for the prevention and complementary treatment of neurological diseases associated with MMP involvement
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Determination of histamine in anchovies - Engraulis encrasicholus (L., 1758) – by capillary zonal electrophoresis: biomedical and commercial considerations
No full textDosaggio di istamina nell’acciuga Engraulis encrasicholus (L., 1758) mediante elettroforesi capillare zonale: considerazione di interesse biomedico e commerciale
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Laminar Order within Langmuir-Blodgett Multilayers from Phospholipid and Myelin Basic Protein: A Neutron Reflectivity Study
No full textMultilayers consisting of negatively charged phospholipid DMPA and myelin basic protein (MBP) were assembled by Langmuir-Blodgett deposition of floating Langmuir monolayers from the air/water interface to solid substrates. Protein/lipid samples were obtained by binding MBP from the aqueous subphase to the phospholipid monolayers before deposition. The vertical organization of these model membranes (i.e., with organization perpendicular to the substrate surface) was investigated in detail by neutron reflectivity measurements, and the internal distribution of water molecules was determined from the change of contrast after in-situ H2O/D2O exchange. The multilayers were well ordered, with repeating lipid bilayers as fundamental structural unit. MBP was inserted in between adjacent lipid headgroups, such as in the natural myelin membrane. Water molecules in the multilayers were present mainly in the lipid headgroup and protein slab. On exposition of the pure lipid multilayers to a dry atmosphere, a reduction of the bilayer spacing was determined, whereas the global lamellar order was not affected. In contrast, drying of the protein/ lipid multilayers induced degradation of the laminar order. The data demonstrate that ordered Langmuir-Blodgett multilayers are versatile model systems for studying how competing interactions between lipid, protein, water, and ions affect the global organization of such multilamellar lipid/protein assemblies. Here, the water molecules were found to be a necessary mediator to maintain the laminar order in a multilayer from DMPA and myelin basic protein
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