Journal of internal medicine
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Review
Manganese toxicity in the central nervous system: the glutamine/glutamate-γ-aminobutyric acid cycle.
Manganese (Mn) is an essential trace element that is required for maintaining proper function and regulation of numerous biochemical and cellular reactions. Despite its essentiality, at excessive levels Mn is toxic to the central nervous system (CNS). ⋯ Its toxicity is associated with disruption of the glutamine (Gln)/glutamate (Glu)-γ-aminobutyric acid (GABA) cycle (GGC) between astrocytes and neurons, thus leading to changes in Glu-ergic and/or GABAergic transmission and Gln metabolism. Here we discuss the common mechanisms underlying Mn-induced neurotoxicity and their relationship to CNS pathology and GGC impairment.
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Comparative Study
Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort.
The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope. ⋯ The levels of MR-proANP and CT-proET-1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.
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Randomized Controlled Trial Multicenter Study Comparative Study
An MRI-based index to measure the severity of Alzheimer's disease-like structural pattern in subjects with mild cognitive impairment.
Structural magnetic resonance imaging (MRI) is sensitive to neurodegeneration and can be used to estimate the risk of converting to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI). Brain changes in AD and prodromal AD involve a pattern of widespread atrophy. The use of multivariate analysis algorithms could enable the development of diagnostic tools based on structural MRI data. In this study, we investigated the possibility of combining multiple MRI features in the form of a severity index. ⋯ We found that joint evaluation of multiple brain regions provided accurate discrimination between progressive and stable MCI, with better performance than hippocampal volume alone, or a limited set of features. A major challenge is still to determine optimal cut-off points for such parameters and to compare their relative reliability.
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T-cell immunotherapy is a promising approach to treat disseminated cancer. However, it has been limited by the ability to isolate and expand T cells restricted to tumour-associated antigens. ⋯ Indeed, genetically engineered T cells have recently been successfully used for cancer treatment in a small number of patients. Here we review the recent progress in the field, and summarize the challenges that lie ahead and the strategies being used to overcome them.
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Findings from preclinical and clinical studies show that vascular normalization represents a novel strategy to enhance the efficacy of and overcome the acquired resistance to anti-angiogenic therapies in cancer. Several mechanisms of tumour vessel normalization have been revealed. Amongst them, secreted class 3 semaphorins (Sema3), which regulate axon guidance and angiogenesis, have been recently identified as novel vascular normalizing agents that inhibit metastatic dissemination by restoring vascular function. Here, we discuss the different biological functions and mechanisms of action of Sema3 in the context of tumour vascular normalization, and their impact on the different cellular components of the tumour microenvironment.