Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection during the neonatal period commonly induces apnea episodes, and the proinflammatory cytokine IL-1beta may serve as a critical mediator between these events. To determine the mechanism by which IL-1beta depresses respiration, we examined a prostaglandin E(2) (PGE(2))-dependent pathway in newborn mice and human neonates. IL-1beta and transient anoxia rapidly induced brainstem-specific microsomal prostaglandin E synthase-1 (mPGES-1) activity in neonatal mice. Furthermore, IL-1beta reduced respiratory frequency during hyperoxia and depressed hypoxic gasping and autoresuscitation in mPGES-1 wild-type mice, but not in mPGES-1 knockout mice. In wild-type mice, PGE(2) induced apnea and irregular breathing patterns in vivo and inhibited brainstem respiratory rhythm generation in vitro. Mice lacking the EP3 receptor (EP3R) for PGE(2) exhibited fewer apneas and sustained brainstem respiratory activity, demonstrating that PGE(2) exerts its respiratory effects via EP3R. In human neonates, the infectious marker C-reactive protein was correlated with elevated PGE(2) in the cerebrospinal fluid, and elevated central PGE(2) was associated with an increased apnea frequency. We conclude that IL-1beta adversely affects breathing and its control by mPGES-1 activation and PGE(2) binding to brainstem EP3 receptors, resulting in increased apnea frequency and hypoxia-induced mortality.
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PMID:The induced prostaglandin E2 pathway is a key regulator of the respiratory response to infection and hypoxia in neonates. 1753

This review considers the contributions to exercise hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O(2) dependent. The early phase of exercise hyperaemia is attributable to K(+) released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K(+) may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator-associated channels, following the fall in intracellular H(+). ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A(2A) receptors, in a nitric oxide-independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O(2) attenuates efflux of H(+) and lactate, thereby decreasing the contribution that adenosine makes to exercise hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE(2) and PGI(2), also accumulate in the interstitium during exercise, and breathing 40% O(2) abolished the contribution of PGs to exercise hyperaemia. This suggests that PGE(2) released from muscle fibres and PGI(2) released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise hyperaemia by improving O(2) supply, limiting the release of O(2)-dependent adenosine and PGs, higher O(2) concentrations may have adverse effects. Evidence is presented that breathing 100% O(2) limits exercise hyperaemia by generating O(2)(-), which inactivates nitric oxide and decreases PG synthesis.
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PMID:Contribution of non-endothelium-dependent substances to exercise hyperaemia: are they O(2) dependent? 2304 41

Topical ocular ketorolac improves the outcomes of severe retinopathy of prematurity and when administered with systemic caffeine, decreases the severity of oxygen-induced retinopathy. We tested the hypothesis that co-cultures of human retinal endothelial cells (HRECs) and human retinal astrocytes (HRAs) on 3-dimensional (3-D) hydrogel scaffolds is a more representative biomimetic paradigm of the blood-retinal-barrier (BRB) than 2-D cultures, and should be utilized for preclinical drug discovery and development. Mono- and co-cultures of HRECs and HRAs were treated with standard doses of ketorolac, ibuprofen, and/or caffeine, and exposed to hyperoxia, intermittent hypoxia (IH), or normoxia on 2-D surfaces or 3-D biodegradable hydrogel scaffolds (AlgiMatrix or Geltrex). Media and cells were collected at 72h post treatment for arachidonic acid metabolites. Cells cultured on 3-D scaffolds exhibited less oxidative stress and variability in drug responses. HRAs enhanced the responses of HRECs to drugs and changes in oxygen environment. PGE2 and PGI2 were the predominant prostanoids produced in response to IH, reflecting COX-2 immunoreactivity. We conclude that HRECs and HRAs co-cultured on 3-D scaffolds may recapitulate drug responses of the dynamic BRB and therefore should be implemented for preclinical ocular drug discovery and development.
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PMID:Human retinal endothelial cells and astrocytes cultured on 3-D scaffolds for ocular drug discovery and development. 2892 62