Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The effects of oxidative stress on DNA damage and associated reactions, increased polyadenosine diphosphate-ribose polymerase (PARP) activity and decreased nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) contents, have been tested in primary cultures of porcine aortic endothelial cells. The cells were treated with 50-500 microM H2O2 for 20 min or 100 microM paraquat for 3 days or were exposed to 95% O2 for 2 and 5 days. The administration of 250-500 microM H2O2 resulted in a marked increase in PARP activity and a profound depletion of ATP and NAD. Although hyperoxia had no effect on PARP activity and reduced only slightly the ATP and NAD stores, it markedly reduced the ability of endothelial cells to increase PARP activity upon exposure to DNase. Paraquat had a similar effect. Human dermal fibroblasts were also exposed to 50-500 microM H2O2 for 20 min or 95% O2 for 5 days. Their response to H2O2 differed from that of endothelial cells by their ability to maintain the ATP content at a normal level. Fibroblasts were also insensitive to the effect of hyperoxia. These results suggest that the oxidant-related DNA damage is a function of the type of oxidative stress used and may be cell-specific.
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PMID:Differential effects of hyperoxia and hydrogen peroxide on DNA damage, polyadenosine diphosphate-ribose polymerase activity, and nicotinamide adenine dinucleotide and adenosine triphosphate contents in cultured endothelial cells and fibroblasts. 250 Apr 51

Oxidants are generated in vivo by multiple mechanisms, including stimulation of leukocytes, hyperoxia, metabolism of arachidonic acid, and the activation of various oxidases. When the biochemical defences to the oxidants are inadequate, injury of tissues results. This injury was observed in rabbits and rhesus monkeys when pulmonary inflammation was induced with phorbol esters or formylated peptide given intrabronchially. We have recently investigated metabolic changes in various cells exposed to oxidants that are generated from stimulated leukocytes, including H2O2, O2, and HOCl. The target cells used were P388D1 murine macrophage-like tumour cells, human peripheral lymphocytes, GM 1380 human fibroblasts and rabbit alveolar macrophages. The oxidants used were H2O2 and PMA stimulated PMNs or neutroplasts. Lysis could only be prevented when catalase was added within the first 30-40 min of H2O2 exposure indicating that early metabolic changes determined the fate of the cell. Within seconds after the addition of H2O2 to P388D1 cells activation of the hexose monophosphate shunt (HMPS) was observed indicative of increased glutathione cycle activity. At the same time DNA strand breaks (determined by an alkaline unwinding technique) were detected. They resulted in the activation of the DNA repair enzyme poly-ADP-ribose polymerase (pADP-RP) within minutes after the addition of H2O2. At the same time ATP and NAD (the substrate of pADP-RP) concentrations dropped and nicotinamide accumulated extracellularly. 10-15 min after oxidant exposure free intracellular Ca++ concentrations determined by Quin 2 fluorescence started to increase due to release from intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidant and protease injury of the lung. 369 17

A previous report from this laboratory (Bender, D.A., Magboul, B.I. and Wynick, D. (1982) Brit. J. Nutr. 48, 119-127) suggested that the hydrolysis of the nicotinamide nucleotides NAD and NADP may be an important factor in controlling the tissue content of these coenzymes. Further studies presented here support this suggestion. Both nuclear poly(ADPribose) synthetase and microsomal NAD glycohydrolase showed activity towards both NAD+ and NADP+, and the two nucleotides were mutually competitive. The reduced nucleotides, NADH and NADPH, were not substrates for either enzyme. In rats that were maintained for 24 h under conditions of hypoxia (O2/N2, 1:9) there was an increase in the proportion of nicotinamide nucleotides present in the liver in the reduced form, and an increase in the total concentration of nucleotides in the liver. In rats that were maintained for 24 h under conditions of hyperoxia (O2/N2, 7:3) there was no change in either the proportion of nicotinamide nucleotides in the liver present in the reduced form or in the total tissue control of the nucleotides. There was an increase in the urinary excretion of kynurenine suggesting an increase in the oxidative metabolism of tryptophan.
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PMID:The role of catabolism in controlling tissue concentrations of nicotinamide nucleotide coenzymes. 630 51

In order to elucidate that which are the factors that may influence the direction of brain activation-induced changes in the redox state of oxidized/reduced nicotinamide adenine dinucleotide (NAD/NADH), the brain cortex was electrically stimulated during arterial hypotension and following reinfusion of the shed blood, during arterial hyper- and hypoxia, and during the second phase of spreading cortical depression (SD). Cerebrocortical NADH fluorescence and vascular volume ( CVV ) of cats, anaesthetized by chloralose, were measured with a microscope fluororeflectometer . Under physiologically normal conditions electrical stimulation resulted in pronounced cortical NAD reduction and increase in CVV . These reactions were not altered by arterial hyperoxia and continuous superfusion of the brain cortex with oxygenated artificial cerebrospinal fluid (mock CSF). Arterial hypotension and SD (in phase II) increased NAD reduction and CVV markedly, and the superimposed electrical stimulation brought about NADH oxidation and greatly depressed CVV responses. Reinfusion of the shed blood did not restore NAD/NADH redox state and CVV to their reference levels, and electrical stimulation under this condition led to NADH oxidation and negligible vascular reactions. Since under physiologically normal conditions electrical activation of the brain cortex resulted in NAD reduction and marked increase in CVV and the magnitude of these reactions were not altered by arterial hyperoxia or by superfusion of the brain cortex with oxygenated CSF, it is very unlikely that the brain cortex became hypoxic during stimulation. Because when the steady NAD/NADH redox state of the brain cortex was shifted toward reduction by arterial hypotension and reinfusion and SD, electrical stimulation led to NADH oxidation, it is suggested that the prestimulatory steady redox state has great importance in determining the direction of NAD/NADH redox reactions evoked by activation of the brain cortex.
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PMID:Determinants of brain activation-induced cortical NAD/NADH responses in vivo. 632 66

Exposure to high fractional inspired oxygen for 24 h increases permeability of the alveolar epithelium, contributing to the clinical manifestations of oxygen toxicity. Utilizing a model of the alveolar epithelium in which isolated rat type II cells form polarized monolayers on polycarbonate filters [transepithelial resistance (R(t)) > 1 k Omega x cm(2) by day 4], we evaluated the ability of reduced glutathione (GSH) to ameliorate these changes. On day 4, apical fluid was replaced with culture medium containing 1) no additives, 2) GSH (500 microM), or 3) GSH (500 microM) + glutathione reductase (0.5 U/ml) + nicotinamide adenine dinucleotide phosphate (250 microM). Monolayers were exposed (for 24 h) to room air (control) or 95% O(2), each containing 5% CO(2). After 24 h of hyperoxia, R(t) for condition 1 decreased by 45% compared with control (P < 0.001). In conditions 2 and 3, R(t) did not decrease significantly (P = not significant). Hyperoxia-induced decreases in active ion transport were observed for conditions 1 and 2 (P < 0.05), but not for condition 3 (P = not significant). These findings indicate that extracellular GSH may protect the alveolar epithelium against hyperoxia-induced injury. Addition of glutathione reductase and nicotinamide adenine dinucleotide phosphate may further augment these protective effects of GSH.
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PMID:Extracellular glutathione inhibits oxygen-induced permeability changes in alveolar epithelial monolayers. 1145 90

Therapy with high oxygen concentrations (hyperoxia) is often necessary to treat patients with respiratory failure. However, hyperoxia may exacerbate the development of acute lung injury, perhaps by increasing lung epithelial cell death. Therefore, interrupting lung epithelial cell death is an important protective and therapeutic strategy. In the present study, hyperoxia (95% O(2)) results in murine lung epithelium cell death by DNA-laddering, terminal deoxynucleotidyltransferase dUTP nick end labeling, and Annexin V-fluorescein isothiocyanate flow cytometry assay. We show that hyperoxia increases superoxide production, as assessed by nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity and flow cytometric assay, and increases phospho-extracellular signal-regulated kinase (ERK)1/2 by Western blot analysis. These processes are inhibited by a reactive oxygen species inhibitor, diphenylene iodonium (DPI), and by an inhibitor of the mitogen-activated protein (MAP) or ERK kinase (MEK)/ERK1/2 pathway, PD98059. ERK1/2 activation in hyperoxia is also inhibited by DPI. Hyperoxia-induced cell death is associated with cytochrome c release, subsequent caspase 9 and 3 activation, and poly (ADP-ribosyl) polymerase cleavage, which can all be suppressed by DPI and PD98059. However, the broad caspase inhibitor z-VAD-FMK protects cells from death without affecting superoxide generation and ERK1/2 activation. Taken together, our data suggest that hyperoxia, by virtue of activating NADPH oxidase, generates reactive oxygen species (ROS), which mediates cell death of lung epithelium via ERK1/2 MAPK activation, and functions upstream of caspase activation in lung epithelial cells.
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PMID:Reactive oxygen species and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase mediate hyperoxia-induced cell death in lung epithelium. 1259 56

Assessment of the oxygenation status of brain tumors has been studied increasingly with imaging techniques in light of recent advances in oncology. Tumor oxygen tension is a critical factor influencing the effectiveness of radiation and chemotherapy and malignant progression. Hypoxic tumors are resistant to treatment, and prognostic value of tumor oxygen status is shown in head and neck tumors. Strategies increasing the tumor oxygenation are being investigated to overcome the compromising [figure: see text] effect of hypoxia on tumor treatment. Administration of nicotinamide and inhalation of various high oxygen concentrations have been implemented. Existing methods for assessment of tissue oxygen level are either invasive or insufficient. Accurate and noninvasive means to measure tumor oxygenation are needed for treatment planning, identification of patients who might benefit from oxygenation strategies, and assessing the efficacy of interventions aimed to increase the radiosensitivity of tumors. Of the various imaging techniques used to assess tissue oxygenation, MR spectroscopy and MR imaging are widely available, noninvasive, and clinically applicable techniques. Tumor hypoxia is related closely to insufficient blood flow through chaotic and partially nonfunctional tumor vasculature and the distance between the capillaries and the tumor cells. Information on characteristics of tumor vasculature such as blood volume, perfusion, and increased capillary permeability can be provided with MR imaging. MR imaging techniques can provide a measure of capillary permeability based on contrast enhancement and relative cerebral blood volume estimates using dynamic susceptibility MR imaging. Blood oxygen level dependent contrast MR imaging using gradient echo sequence is intrinsically sensitive to changes in blood oxygen level. Animal models using blood oxygen level-dependent contrast imaging reveal the different responses of normal and tumor vasculature under hyperoxia. Normobaric hyperoxia is used in MR studies as a method to produce MR contrast in tissues. Increased T2* signal intensity of brain tissue has been observed using blood oxygen level-dependent contrast MR imaging. Dynamic blood oxygen level-dependent contrast MR imaging during hyperoxia is suggested to image tumor oxygenation. Quantification of cerebral oxygen saturation using blood oxygen level-dependent MR imaging also has been reported. Quantification of cerebral blood oxygen saturation using MR imaging has promising clinical applications; however, technical difficulties have to be resolved. Blood oxygen level dependent MR imaging is an emerging technique to evaluate the cerebral blood oxygen saturation, and it has the potential and versatility to assess oxygenation status of brain tumors. Upon improvement and validation of current MR techniques, better diagnostic, prognostic, and treatment monitoring capabilities can be provided for patients with brain tumors.
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PMID:Hypoxia imaging in brain tumors. 1268 10

We present a case study of a newborn girl with a reduced erythrocytic nicotinamide adenine dinucleotide (NADH)-dependent methaemoglobin reductase level. Within the first days of life she developed cyanosis due to a methaemoglobin level of 21%. The hyperoxia test was characteristic, with normal increases in blood oxygen tension, whereas the oxygen saturation remained constant at 92%. Over the next months the methaemoglobin level decreased to 10%, and the girl did well without treatment.
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PMID:[Congenital methaemoglobinaemia: an infrequent cause of neonatal cyanosis]. 1876 34

Quantification of nicotinamide adenine dinucleotide (NADH) changes during functional brain activation and pathological conditions provides critical insight into brain metabolism. Of the different imaging modalities, two-photon laser scanning microscopy (TPLSM) is becoming an important tool for cellular-resolution measurements of NADH changes associated with cellular metabolic changes. However, NADH fluorescence emission is strongly absorbed by hemoglobin. As a result, in vivo measurements are significantly affected by the hemodynamics associated with physiological and pathophysiological manipulations. We model NADH fluorescence excitation and emission in TPLSM imaging based on precise maps of cerebral microvasculature. The effects of hemoglobin optical absorption and optical scattering from red blood cells, changes in blood volume and hemoglobin oxygen saturation, vessel size, and location with respect to imaging location are explored. A simple technique for correcting the measured NADH fluorescence intensity changes is provided, with the utilization of a parallel measurement of a physiologically inert fluorophore. The model is applied to TPLSM measurements of NADH fluorescence intensity changes in rat somatosensory cortex during mild hypoxia and hyperoxia. The general approach of the correction algorithm can be extended to other TPLSM measurements, where changes in the optical properties of the tissue confound physiological measurements, such as the detection of calcium dynamics.
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PMID:Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response. 2202 50

Ventilation with enhanced fractions of O(2) (hyperoxia) is a common and necessary treatment for hypoxemia in patients with lung failure, but prolonged exposure to hyperoxia causes lung injury. Ischemia-reperfusion (IR) injury of lung tissue is common in lung transplant or crush injury to the chest. These conditions are associated with apoptosis and decreased survival of lung tissue. The objective of this work is to use cryoimaging to evaluate the effect of exposure to hyperoxia and IR injury on lung tissue mitochondrial redox state in rats. The autofluorescent mitochondrial metabolic coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are electron carriers in ATP generation. These intrinsic fluorophores were imaged for rat lungs using low-temperature fluorescence imaging (cryoimaging). Perfused lungs from four groups of rats were studied: normoxia (control), control perfused with an mitochondrial complex IV inhibitor (potassium cyanide, KCN), rats exposed to hyperoxia (85% O(2)) for seven days, and from rats subjected to lung IR in vivo 24 hours prior to study. Each lung was sectioned sequentially in the transverse direction, and the images were used to reconstruct a three-dimensional (3-D) rendering. In KCN perfused lungs the respiratory chain was more reduced, whereas hyperoxic and IR lung tissue have a more oxidized respiratory chain than control lung tissue, consistent with previously measured mitochondrial dysfunction in both hyperoxic and IR lungs.
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PMID:Optical imaging of tissue mitochondrial redox state in intact rat lungs in two models of pulmonary oxidative stress. 2255 88


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