Search results for "Prague"
showing 10 items of 652 documents
Inhibition of Mitochondrial Function by Efavirenz Increases Lipid Content in Hepatic Cells
2010
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) widely used in human immunodeficiency virus (HIV) infection therapy. It has been associated with hepatotoxic effects and alterations in lipid and body fat composition. Given the importance of the liver in lipid regulation, we have evaluated the effects of clinically used concentrations of EFV on the mitochondria and lipid metabolism of human hepatic cells in vitro. Mitochondrial function was rapidly undermined by EFV to an extent that varied with the concentration employed; in particular, respiration and intracellular adenosine triphosphate (ATP) levels were reduced whereas reactive oxygen species (ROS) production i…
Efavirenz induces interactions between leucocytes and endothelium through the activation of Mac-1 and gp150,95
2013
The potential cardiovascular (CV) toxicity associated with combined antiretroviral therapy (cART) has been attributed mainly to the nucleoside reverse transcriptase inhibitors abacavir and didanosine. However, the other two components of cART--non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)--may also be implicated, either directly or by influencing the action of the other drugs. This study evaluates the acute direct effects of the NNRTIs efavirenz and nevirapine and one of the most widely employed PIs, lopinavir, on leucocyte-endothelium interactions, a hallmark of CV disease.Drugs were analysed in vitro in human cells (interactions of peripheral blood…
Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia
2004
This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O(2)) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced…
Extracellular site of action of phenylalkylamines on L-type calcium current in rat ventricular myocytes.
1995
The effects of the phenylalkylamines verapamil, gallopamil, and devapamil on L-type calcium currents (ICa) were studied in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. In particular, the question was addressed, whether the pharmacological binding sites for these drugs were located at the inner and/or at the outer surface of the cell membrane. Therefore, tertiary verapamil, gallopamil, and devapamil and their corresponding quaternary derivatives were applied either from the outside or the inside of the cell membrane. Extracellular application of verapamil, gallopamil and devapamil (each at 3 microM) reduced ICa to 16.1 +/- 8.6%, 11 +/- 8.9%, and 9.3 +/- 6%…
The effect of long context exposure on cued conditioning and c-fos expression in the rat forebrain
2004
The c-fos expression was used to study the neural substrates of the cued fear conditioning acquisition, preceded by a short exposure versus a long exposure to the conditioning context. A long-context exposure (either during the night or during the day) prior to conditioning, was associated with low freezing in the learning test. Differences in the c-fos expression of CA1, CA3, BL Amygdala, LS and BNST were found between the short- or long-context groups with a pre-exposure before cued conditioning. Ce Amygdala showed no differences in the c-fos expression labeling. We reported the hippocampal c-fos activation during the cued fear conditioning acquisition. Specifically, the CA1 activation co…
Synaptic release of zinc from brain slices: factors governing release, imaging, and accurate calculation of concentration.
2006
Cerebrocortical neurons that store and release zinc synaptically are widely recognized as critical in maintenance of cortical excitability and in certain forms of brain injury and disease. Through the last 20 years, this synaptic release has been observed directly or indirectly and reported in more than a score of publications from over a dozen laboratories in eight countries. However, the concentration of zinc released synaptically has not been established with final certainty. In the present work we have considered six aspects of the methods for studying release that can affect the magnitude of zinc release, the imaging of the release, and the calculated concentration of released zinc. We…
Functional feature of a novel model of blood brain barrier: Studies on permeation of test compounds
2001
Drug delivery to the central nervous system (CNS) is subject to the permeability limitations imposed by the blood-brain barrier (BBB). Several systems in vitro have been described to reproduce the physical and biochemical behavior of intact BBB, most of which lack the feature of the in vivo barrier. We developed a fully formed monolayer of RBE4.B immortalized rat brain microvessel endothelial cells (ECs), grown on top of polycarbonate filter inserts with cortical neuronal cells grown on the outside. Neurons induce ECs to synthesize and sort occludin to the cell periphery. Occludin localization is regulated by both compositions of the substratum and soluble signals released by cortical co-cu…
Expression of the transcription factor Pax6 in the adult rat dentate gyrus
2005
The transcription factor Pax 6 is expressed in precursor cells during embryonic CNS development, and it plays an important role in the regulation of cell proliferation and neuronal fate determination. Pax 6-expressing cells are also present in the adult hippocampal dentate gyrus and subventricular zone/rostral migratory stream, regions in which neuronal precursors exist during adult life. In the adult dentate gyrus, precursor cells are located in the innermost portion of the granule cell layer, and Pax 6-expressing nuclei are most abundant in this region. To examine the putative role of Pax 6 in adult hippocampal neurogenesis, we have studied the proliferative activity, distribution, and ph…
Chronic non-invasive glucocorticoid administration decreases polysialylated neural cell adhesion molecule expression in the adult rat dentate gyrus
2004
The expression of the polysialylated neural cell adhesion molecule (PSA-NCAM) is increased in the hippocampus after chronic restraint stress (CRS) and may play a permissive role in structural changes that include dendrite reorganization in dentate gyrus (DG) and CA3 pyramidal neurons and suppression of neurogenesis in DG. We report that chronic oral corticosterone (CORT) administration decreases the number of PSA-NCAM immunoreactive granule neurons in the adult rat dentate gyrus, and the available evidence suggests that this is an indirect effect of CORT, possibly involving excitatory amino acids, that may not be directly related to neurogenesis. Because CORT treatment reduces but does not …
Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain
2006
Neural progenitor cells (NPCs) reside within the subventricular zone (SVZ) in rodents. These NPCs give rise to neural precursors in adults that migrate to the olfactory bulb (OB) along a well-defined pathway, the rostral migratory stream (RMS). Here we demonstrate that these NPCs can be labeled, in vivo, in adult rats with fluorescent, micron-sized iron oxide particles (MPIOs), and that magnetic resonance imaging (MRI) can detect migrating neural precursors carrying MPIOs along the RMS to the OB. Immunohistochemistry and electron microscopy indicated that particles were inside GFAP(+) neural progenitor cells in the SVZ, migrating PSA-NCAM(+) and Doublecortin(+) neural precursors within the …