Institution
University of Coimbra
Education•Coimbra, Portugal•
About: University of Coimbra is a education organization based out in Coimbra, Portugal. It is known for research contribution in the topics: Population & Context (language use). The organization has 14318 authors who have published 43067 publications receiving 994733 citations. The organization is also known as: UC & Universidade dos Estudos Gerais.
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TL;DR: This study investigated whether seizures can be effectively inhibited by blocking the brain production of IL‐1β, by using selective inhibitors of interleukin‐converting enzyme (ICE/caspase‐1) or through caspase-1 gene deletion.
Abstract: Summary: Purpose: Cytokines and related inflammatory mediators are rapidly synthesized in the brain during seizures. We previously found that intracerebral administration of interleukin-1 (IL-1)-β has proconvulsant effects, whereas its endogenous receptor antagonist (IL-1Ra) mediates potent anticonvulsant actions in various models of limbic seizures. In this study, we investigated whether seizures can be effectively inhibited by blocking the brain production of IL-1β, by using selective inhibitors of interleukin-converting enzyme (ICE/caspase-1) or through caspase-1 gene deletion.
Methods: Caspase-1 was selectively blocked by using pralnacasan or VX-765. IL-1β release was induced in mouse organotypic hippocampal slice cultures by proinflammatory stimuli [lipopolysaccaride (LPS) + adenosine triphosphate (ATP)] and measured with enzyme-linked immunosorbent assay (ELISA). IL-1β production during seizures was measured in the rat hippocampus by Western blot. Seizures were induced in freely moving mice and rats by intrahippocampal injection of kainic acid and recorded by EEG analysis.
Results: Caspase-1 inhibition reduced the release of IL-1β in organotypic slices exposed to LPS+ATP. Administration of pralnacasan (intracerebroventricular, 50 μg) or VX-765 (intraperitoneal, 25–200 mg/kg) to rats blocked seizure-induced production of IL-1β in the hippocampus, and resulted in a twofold delay in seizure onset and 50% reduction in seizure duration. Mice with caspase-1 gene deletion showed a 70% reduction in seizures and an approximate fourfold delay in their onset.
Conclusions: Inhibition of caspase-1 represents an effective and novel anticonvulsive strategy, which acts by selectively reducing the brain availability of IL-1β.
171 citations
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TL;DR: This work has mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified four independent mutations in MFRP, a gene that is selectively expressed in the eye and encodes a protein with homology to Tolloid proteases and the Wnt-binding domain of the Frizzled transmembrane receptors.
Abstract: Nanophthalmos is a rare disorder of eye development characterized by extreme hyperopia (farsightedness), with refractive error in the range of +8.00 to +25.00 diopters. Because the cornea and lens are normal in size and shape, hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. Thickening of these tissues is a general feature of axial hyperopia, whereas the opposite occurs in myopia. We have mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified four independent mutations in MFRP, a gene that is selectively expressed in the eye and encodes a protein with homology to Tolloid proteases and the Wnt-binding domain of the Frizzled transmembrane receptors. This gene is not critical for retinal function, as patients entirely lacking MFRP can still have good refraction-corrected vision, produce clinically normal electro-retinograms, and show only modest anomalies in the dark adaptation of photoreceptors. MFRP appears primarily devoted to regulating axial length of the eye. It remains to be determined whether natural variation in its activity plays a role in common refractive errors.
171 citations
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TL;DR: In this paper, the authors integrate the available information to provide a theoretical interpretation of the recent physicochemical and biological changes in the Mondego estuarine ecosystem, which will be further used as basic framework for the development of a structurally dynamic model.
171 citations
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TL;DR: This work uses both model dependent and independent techniques to assess the difference between dissolution profiles in which ibuprofen, in the form of uncoated pellets, is used as a model drug.
171 citations
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TL;DR: In this paper, a new approach was described to produce nanostructured electrocatalytic membranes using a combination of three methods: layer-by-layer technique, PAMAM dendrimers with cobalt hexacyanoferrates-modified gold nanoparticles were alternated with poly(vinylsulfonic acid) layers on ITO (indium tin oxide) electrodes.
171 citations
Authors
Showing all 14693 results
Name | H-index | Papers | Citations |
---|---|---|---|
P. Chang | 170 | 2154 | 151783 |
Yang Gao | 168 | 2047 | 146301 |
Bin Liu | 138 | 2181 | 87085 |
P. Sinervo | 138 | 1516 | 99215 |
Filipe Veloso | 128 | 887 | 75496 |
Panagiotis Kokkas | 128 | 1234 | 81051 |
Nuno Filipe Castro | 128 | 960 | 76945 |
Robert Gardner | 128 | 1015 | 77619 |
Francois Corriveau | 128 | 1022 | 75729 |
Peter Krieger | 128 | 1171 | 81368 |
João Carvalho | 126 | 1278 | 77017 |
Helmut Wolters | 126 | 851 | 75721 |
Nicola Venturi | 126 | 796 | 69518 |
Sai-Juan Chen | 121 | 1211 | 73991 |
Harinder Singh Bawa | 120 | 798 | 66120 |