Adv Exp Med Biol
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In chronic airway inflammatory disorders, such as asthma, glucocorticoid (GC) insensitivity is a challenging clinical problem associated with life-threatening disease progression and the potential development of serious side effects. The mechanism of steroid resistance in asthma remains unclear and may be multifactorial. Excluding noncompliance with GC treatment, abnormal steroid pharmacokinetics, and rare genetic defects in the glucocorticoid receptor (GR), the majority of GC insensitivity in asthma can be attributed to secondary defects related to GR function. ⋯ Since T cells, eosinophils, and monocytes play a major role in the pathogenesis of airway inflammation, most of the work published to date has focused on these cell types as the primary therapeutic targets in GC-insensitive asthma. We herein review several distinct techniques for the assessment of (1) the cellular response to GCs including the effect of GCs on cell viability, adhesion, and mediator release; (2) the functionality of GC receptors, including phosphorylation of the GR, nuclear translocation, and binding activities; and (3) the characterization of proteins differentially expressed in steroid-resistant cells by comparative 2DE-gel electrophoresis-based techniques and mass spectrometry. These comprehensive approaches are expected to reveal novel candidates for biomarkers of steroid insensitivity, which may lead to the development of effective therapeutic interventions for patients with chronic steroid-resistant asthma.
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Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. ⋯ While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides are likely to emerge as neural and endocrine messengers in orchestrating the microbiota-gut-brain axis in health and disease.
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Review
Nanoceria as bona fide catalytic antioxidants in medicine: what we know and what we want to know….
Cerium oxide (CeO2) nanoparticles, CeNPs or nanoceria are inorganic and possess catalytic antioxidant activity. They scavenge reactive oxygen species and act as an oxygen buffer. Their application in industry is well-established. ⋯ We highlight studies that examine how CeNPs behave in biological environments and how they interact with bio-macromolecules. We also discuss studies that examine the dynamic changes of the surface chemistry of CeNPs in physiological buffers. Finally, we raise a list of questions that we think ought to be answered for CeNPs to be considered the antioxidants of choice in medicine, specifically in the treatment of ocular diseases.
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In most team sports, intermittent high intensity sprint efforts combined with short recovery periods have been identified as a key factor of physical performance; the ability to repeat these efforts at a sustained level is of great importance. Near-infrared spectroscopy (NIRS) has been proposed as a tool to monitor muscle oxygenation changes during such sprint efforts. The purpose of this study was to observe muscle reoxygenation rate (reoxy rate) (% s⁻¹) between sprint efforts in a repeat sprint cycle test. ⋯ The simplest explanation for the increase in desaturation following training is an increase in muscle oxygen consumption due to an increase in mitochondrial content. This results in an increased extraction of delivered oxygen as confirmed by the HHb data. In conclusion, NIRS is able to measure positive training effects on muscle oxygen extraction, at the level of the individual elite athlete.
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The relationship between cerebral autoregulation (CA) and the neurotoxic effects of anaesthesia with and without surgery is investigated. Newborn piglets were randomly assigned to receive either 6 h of anaesthesia (isoflurane) or the same with an additional hour of minor surgery. ⋯ Presence of CA impairment was not significant but found to increase with surgical exacerbation. The impairment did not correlate with histological outcome (presence of cell death, apoptosis and microglial activation in the brain).