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

Stroke causes heterogeneous changes in tissue oxygenation, with a region of decreased blood flow, the penumbra, surrounding a severely damaged ischemic core. Treatment of acute ischemic stroke aims to save this penumbra before its irreversible damage by continued ischemia. However, effective treatment remains elusive due to incomplete understanding of processes leading to penumbral death. While oxygenation is central in ischemic neuronal death, it is unclear exactly what actual changes occur in interstitial oxygen tension (pO2) in ischemic regions during stroke, particularly the penumbra. Using the unique capability of in vivo electron paramagnetic resonance (EPR) oximetry to measure localized interstitial pO2, we measured both absolute values, and temporal changes of pO2 in ischemic penumbra and core during ischemia and reperfusion in a rat model. Ischemia rapidly decreased interstitial pO2 to 32% +/- 7.6% and 4% +/- 0.6% of pre-ischemic values in penumbra and core, respectively 1 hour after ischemia. Importantly, whilst reperfusion restored core pO2 close to its pre-ischemic value, penumbral pO2 only partially recovered. Hyperoxic treatment significantly increased penumbral pO2 during ischemia, but not in the core, and also increased penumbral pO2 during reperfusion. These divergent, important changes in pO2 in penumbra and core were explained by combined differences in cellular oxygen consumption rates and microcirculation conditions. We therefore demonstrate that interstitial pO2 in penumbra and core is differentially affected during ischemia and reperfusion, providing new insights to the pathophysiology of stroke. The results support normobaric hyperoxia as a potential early intervention to save penumbral tissue in acute ischemic stroke.
 ...
PMID:Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats. 1509 Nov 15

Nerve regeneration in diabetes is essential for reversal of neuropathy as well as the recovery of nerves from injury due to acute nerve compression and entrapment. Endoneural hypoxia due to hyperglycemia-induced blood flow reductions is observed early in the course of diabetes, and the resultant ischemia plays a role in the diminished neural regeneration. Hyperbaric oxygen therapy is capable of producing tissue hyperoxia by raising oxygen tensions in ischemic tissues, and was shown to be beneficial in the reversal of experimental ischemic neuropathy. In this study, an experimental diabetes model was used to evaluate the functional and histomorphological effects of hyperbaric oxygen therapy on early diabetic nerve regeneration. Our results indicate that there is significant histomorphological impairment of nerve regeneration, even in very early stages of diabetes. However, no beneficial effects of hyperbaric oxygen therapy could be demonstrated at this stage.
 ...
PMID:Effect of hyperbaric oxygen therapy on nerve regeneration in early diabetes. 1516 Mar 86

There is mounting evidence both from experimental and clinical studies that traumatic brain injury (TBI) is associated with a reduction of aerobic metabolism. This results from a variable combination of impaired substrate delivery and mitochondrial failure. Mitochondria, which are responsible for the production of 95% of cell adenosine triphosphate (ATP), may become compromised after TBI. On the other hand, in the very early period after the primary injury, oxygen delivery may be impaired due to arterial hypoxia and/or to a reduction of cerebral blood flow (CBF). As a consequence, 80-90% of patients who die of head injury show ischemia on histo-pathological examination of the brain tissue. In the absence of an appropriate treatment for TBI, these observations favored the hypothesis that manipulation of brain oxygen delivery could be a therapeutic tool to improve aerobic metabolism. Several strategies were developed, including the increase of cerebral perfusion pressure (CPP) using amines or the increase of arterial partial pressure of oxygen (PaO(2)) through hyperbaric oxygen (HBO) or normobaric hyperoxia. Several experimental and clinical studies, using normobaric hyperoxia, demonstrated an increase in brain tissue oxygen tension and a reduction of brain extracellular lactate levels, but there is no consensus about the biological meaning of these findings. For some authors, they translate an improvement of brain oxidative metabolism, while for others they represent only biological epiphenomena. The current review addresses the rational behind normobaric hyperoxia as a therapeutic application and discusses the experimental and clinical results achieved so far.
 ...
PMID:Arterial hyperoxia in severe head injury: a useful or harmful option? 1528 92

We have shown that hyperoxia reduces brain damage in a rat model of hypoxia-ischemia. The purpose of this study was to examine the possibility of hyperoxia in inducing vision-threatening retinopathy. Two different experiments were conducted in this study. PART 1: seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37 degrees C). Pups were treated with 100% oxygen at 1 ATA, 1.5 ATA, and 3.0 ATA for a duration of 1 h. PART 2: Newborn rat pups were exposed to 100% oxygen at 1, 1.5, or 3.0 ATA for 1 h, the same treatment protocol used for brain protection after hypoxia-ischemia. Retinopathy was evaluated by the degree of neovascularization (measuring retinal vascular density), by the structural abnormalities (histology) in the retina, and by the expression of hypoxia-hyperoxia sensitive proteins including hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) at 24 h, 1, 2, and 10 weeks after hyperoxia exposure. Hyperoxic treatment at all pressures administered significantly reduced the hypoxia-ischemic-induced reduction in brain weight. Retinal vascular density measurements revealed no signs of neovascularization after hyperoxia exposure. There were also no abnormalities in the structure of the retina and no changes in the protein expression of HIF-1alpha and VEGF following hyperoxia exposure. Exposure to hyperoxia for 1 h at normobaric or hyperbaric pressures did not result in the structural changes or abnormal vascularization that is associated with retinopathy of prematurity, suggesting that hyperoxia is a safe treatment for hypoxic newborn infants.
 ...
PMID:Transient exposure of rat pups to hyperoxia at normobaric and hyperbaric pressures does not cause retinopathy of prematurity. 1529 45

Vascular endothelial growth factor (VEGF) plays a central role in the development of ocular neovascularization (NV) and is an excellent target for therapeutic intervention. VEGF acts through several receptors, including VEGF receptor 1, VEGF receptor 2, neuropilin-1 (Npn1), and Npn2, but the exact role of these receptors in the development of retinal NV is unknown. In this study, we investigated the expression of npn2 mRNA during new blood vessel growth in the retina and used npn2 knockout mice to assess the impact of deficiency of Npn2 on retinal NV. The level of npn2 mRNA in the retina increased during retinal vascular development, after exposure to hyperoxia, and after the onset of retinal ischemia. Immunohistochemistry showed colocalization of Npn2 with a vascular marker in retinal NV. Compared with littermate controls, mice deficient in Npn2 had significantly less ischemia-induced retinal NV and very little subretinal NV due to expression of a Vegf transgene. These data suggest that Npn2 facilitates VEGF-induced retinal NV and may constitute a useful target for therapeutic intervention in ocular diseases complicated by NV.
 ...
PMID:Deficiency of neuropilin 2 suppresses VEGF-induced retinal neovascularization. 1550 78

Hyperoxic pretreatment (>95% O(2)) can evoke myocardial adaptation to ischemia, a method which is potentially clinically usable. We wanted to investigate the role of tumor necrosis factor alpha (TNFalpha) and its p55 receptor (receptor I) in signaling of hyperoxic adaptation to ischemia. Mice deficient for TNFalpha (TNFalpha -/-) or the TNF receptor I (TNFRI -/-) gene and their wild types were subjected to 60 minutes of hyperoxia or sham treatment. Their lungs were then collected for immunoblotting, their hearts isolated and subjected to global ischemia and reperfusion in a Langendorff system, and aortic rings mounted in organ baths for reactivity studies. Hyperoxia increased expression of TNFalpha and TNFalpha converting enzyme in pulmonary proteins from wild type mice, in which hyperoxia increased myocardial tolerance to ischemia. Post-ischemic heart function was improved and infarct size reduced in wild type mice, but not in TNFalpha -/- or TNFRI -/-. The contractile response to TNFalpha on aortic rings was attenuated by hyperoxic pretreatment and by TNFRI -/-. Thus we conclude that TNFalpha, acting through TNFRI, appears important for the protective effects of hyperoxia.
 ...
PMID:Role of tumor necrosis factor alpha and its receptor I in preconditioning by hyperoxia. 1561 39

The present study was undertaken to test whether inhibition of the proangiogenic inflammatory cytokine tumor necrosis factor (TNF)-alpha can modulate retinal hypoxia and preretinal neovascularization in a murine model of oxygen-induced retinopathy (OIR). OIR was produced in TNF-alpha-/- and wild-type (WT) control C57B6 neonatal mice by exposure to 75% oxygen between postnatal days 7 and 12 (P7 to P12). Half of each WT litter was treated with the cytokine inhibitor semapimod (formerly known as CNI-1493) (5 mg/kg) by daily intraperitoneal injection from the time of reintroduction to room air at P12 until P17. The extent of preretinal neovascularization and intraretinal revascularization was quantified by image analysis of retinal flat-mounts and retinal hypoxia correlated with vascularization by immunofluorescent localization of the hypoxia-sensitive drug pimonidazole (hypoxyprobe, HP). HP adducts were also characterized by Western analysis and quantified by competitive enzyme-linked immunosorbent assay. TNF-alpha-/- and WT mice showed a similar sensitivity to hyperoxia-induced retinal ischemia at P12. At P13 some delay in early reperfusion was evident in TNF-alpha-/- and WT mice treated with semapimod. However, at P17 both these groups had significantly better vascular recovery with less ischemic/hypoxic retina and preretinal neovascularization compared to untreated retinopathy in WT mice. Immunohistochemistry showed deposition of HP in the avascular inner retina but not in areas underlying preretinal neovascularization, indicating that such aberrant vasculature can reduce retinal hypoxia. Inhibition of TNF-alpha significantly improves vascular recovery within ischemic tissue and reduces pathological neovascularization in OIR. HP provides a useful tool for mapping and quantifying tissue hypoxia in experimental ischemic retinopathy.
 ...
PMID:Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy. 1568 45

Bcl-2 is a death repressor that protects cells from apoptosis mediated by a variety of stimuli. Bcl-2 expression is regulated by both pro- and anti-angiogenic factors; thus, it may play a central role during angiogenesis. However, the role of bcl-2 in vascular development and growth of new vessels requires further delineation. In this study, we investigated the physiological role of bcl-2 in development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Mice deficient in bcl-2 exhibited a significant decrease in retinal vascular density compared to wild-type mice. This was attributed to a decreased number of endothelial cells and pericytes in retinas from bcl-2-/- mice. We observed, in bcl-2-/- mice, delayed development of retinal vasculature and remodeling, and a significant decrease in the number of major arteries, which branch off from near the optic nerve. Interestingly, hyaloid vessel regression, an apoptosis-dependent process, was not affected in the absence of bcl-2. The retinal vasculature of bcl-2-/- mice exhibited a similar sensitivity to hyperoxia-mediated vessel obliteration compared to wild-type mice during OIR. However, the degree of ischemia-induced retinal neovascularization was significantly reduced in bcl-2-/- mice. These results suggest that expression of bcl-2 is required for appropriate development of retinal vasculature as well as its neovascularization during OIR.
 ...
PMID:Attenuation of retinal vascular development and neovascularization during oxygen-induced ischemic retinopathy in Bcl-2-/- mice. 1570 69

The aim of the present work was to simulate the oxygenation of the whole retina under normal conditions as well as during retinal ischemia. A differential equation describing how oxygen is transported from blood to tissue, diffuses through the tissue and is consumed according to Michaelis-Menten kinetics was constructed. The outer retina was divided into three regions of which one was set to have consumption. The inner retina was considered as one uniform region with respect to maximal rate of oxygen consumption and blood flow. The results suggest that extreme hyperoxia would be needed to make the choroid capable of supplying the whole retina during total retinal artery occlusion and moreover confirm that light might to some extent be beneficial. As supplying 100% oxygen by nose cannula or common oxygen mask can hardly increase the arterial oxygen tension to the levels needed to rescue the whole retina, the effects of oxygen treatment of total retinal artery occlusion are expected to be modest, both in darkness and light, unless a non-rebreather face mask system is used.
 ...
PMID:Theoretical estimation of retinal oxygenation during retinal artery occlusion. 1571 29

Pulmonary oxidant stress plays an important pathogenetic role in disease conditions including acute lung injury/adult respiratory distress syndrome (ALI/ARDS), hyperoxia, ischemia-reperfusion, sepsis, radiation injury, lung transplantation, COPD, and inflammation. Reactive oxygen species (ROS), released from activated macrophages and leukocytes or formed in the pulmonary epithelial and endothelial cells, damage the lungs and initiate cascades of pro-inflammatory reactions propagating pulmonary and systemic stress. Diverse molecules including small organic compounds (e.g. gluthatione, tocopherol (vitamin E), flavonoids) serve as natural antioxidants that reduce oxidized cellular components, decompose ROS and detoxify toxic oxidation products. Antioxidant enzymes can either facilitate these antioxidant reactions (e.g. peroxidases using glutathione as a reducing agent) or directly decompose ROS (e.g. superoxide dismutases [SOD] and catalase). Many antioxidant agents are being tested for treatment of pulmonary oxidant stress. The administration of small antioxidants via the oral, intratracheal and vascular routes for the treatment of short- and long-term oxidant stress showed rather modest protective effects in animal and human studies. Intratracheal and intravascular administration of antioxidant enzymes are being currently tested for the treatment of acute oxidant stress. For example, intratracheal administration of recombinant human SOD is protective in premature infants exposed to hyperoxia. However, animal and human studies show that more effective delivery of drugs to cells experiencing oxidant stress is needed to improve protection. Diverse delivery systems for antioxidants including liposomes, chemical modifications (e.g. attachment of masking pegylated [PEG]-groups) and coupling to affinity carriers (e.g. antibodies against cellular adhesion molecules) are being employed and currently tested, mostly in animal and, to a limited extent, in humans, for the treatment of oxidant stress. Further studies are needed, however, in order to develop and establish effective applications of pulmonary antioxidant interventions useful in clinical practice. Although beyond the scope of this review, antioxidant gene therapies may eventually provide a strategy for the management of subacute and chronic pulmonary oxidant stress.
 ...
PMID:Antioxidant strategies in respiratory medicine. 1640 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>