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)

Specific changes in composition and content of lung extracellular matrix (ECM) proteoglycans (PGs) and hyaluronan (HA) have been observed during the acute response to damage in several forms of injury including infant respiratory distress syndrome (IRDS). These ECM components are thought to modulate the healing response. Hyperoxia, a contributing factor to IRDS, is known to damage both adult and developing lung, however, the extent and pattern of impairment depends on lung maturity. We hypothesized that exposing neonatal rats to hyperoxia alone might result in changes in lung HA, as well as in age-specific changes in lung PGs, similar to those shown to occur in IRDS. In control rats, lung HA decreased over the first 10 days of life, whereas rats exposed to hyperoxia exhibited a time-dependent, time-limited increase in both lung HA and lung wet weight. Histochemistry showed the HA in hyperoxia-exposed lungs to be accumulated in perivascular cuffs of medium sized arteries, and in the alveolar walls. Rats were then exposed to normoxia or hyperoxia for 7 days beginning at either 3 days of life (neonatal) or 21 days (adolescent), and lung tissue was cultured in the presence of [35S]-sulfate to label newly synthesized PGs. Proteoglycans were extracted, and analyzed by isopycnic CsCl gradient centrifugation, sequential enzymatic deglycosylation, size chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). When controlled for total protein extracted, 63% more label was incorporated into large molecular weight material in the tissue exposed to hyperoxia, with a 95% increase in incorporation in the most dense fraction, D1. [35S]-Sulfate incorporation into chondroitin and dermatan sulfate in hyperoxic tissue specifically increased 116% (242% in the D1 fraction), while incorporation into heparan sulfate remained essentially unchanged. There was a nearly fivefold increase in [35S]-sulfate incorporation into chondroitin sulfate chains in the D1 fraction. When the D1 fractions of extracts of treated and control rat lungs were compared on SDS-PAGE, a large chondroitin sulfate proteoglycan (CSPG; core protein of 195 kDa) was upregulated in the D1 fraction from hyperoxic tissue of neonatal rats, but was not detected in the lungs of adolescent animals exposed to hyperoxia. This CSPG and four additional large CSPGs were noted to be upregulated on western blotting by a polyclonal antibody directed against the G1 domain of the aggrecan protein core. We conclude that hyperoxia alone causes an increase in lung HA and lung water, and speculate that this contributes significantly to the clinical syndrome of IRDS. In addition, several large CSPGs are upregulated by hyperoxic exposure in a developmentally specific manner. We speculate that this increase in CSPGs may interfere with the normal developmental sequence of events, contributing to hypoalveolarization.
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PMID:Hyperoxia alone causes changes in lung proteoglycans and hyaluronan in neonatal rat pups. 757

To determine the effects of electrical hypoglossal nerve and submental stimulation on upper airway collapsibility, we examined the pressure-volume (P-V) relationships during bilateral supramaximal stimulation of the distal cut hypoglossal nerve ends over a range of frequencies from zero to 100 Hz in the sealed upper airway of 10 anesthetized supine dogs. Animals were artificially ventilated with 50% O2 and maintained under relative hyperoxia and hypocapnia during the study to eliminate the ventilatory drive output. Sealed upper airway pressures were obtained during random injections of different volumes of air from zero to 50 ml with and without hypoglossal nerve stimulation, and the upper airway P-V curves were obtained. The characteristics of the P-V curves were as follows: (1) the upper airway compliance defined as the slope of the regression of P-V curves fell from 4.07 +/- 0.33 ml/cm H2O without stimulation to 3.02 +/- 0.30 ml/cm H2O with stimulation at 50 Hz and plateaued at frequencies greater than 50 Hz, and (2) the volume at a given pressure during stimulation was larger than that without stimulation. The effects of submental stimulation on upper airway collapsibility were similar to those of hypoglossal nerve stimulation. These results suggest that the increase of upper airway muscle tone by hypoglossal nerve or submental stimulation stiffens the upper airway and that increases in muscle tone expand the upper airway.
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PMID:Hypoglossal nerve stimulation affects the pressure-volume behavior of the upper airway. 784 6

Young rats are thought to be more tolerant to hyperoxia. We propose that this may not be proven and depends on how tolerance is defined. We assessed oxygen tolerance in Sprague-Dawley rats from birth to maturity by comparing survival, lung water, antioxidant enzyme activity, lung morphometrics, heart weight, and arterial blood gases in newborn and 27-, 44-, 48-, and 96-day-old rats exposed to 100% O2 or room air for 22 days. Some 96-day-old rats (rest group) received only 50% O2 between 48 and 72 h. Mortality after 5 days of O2 was 0% in newborn and 27-day-old rats and 27% in 44-day-old rats but was > 80% in 48- and 96-day-old rats. Between 5 and 22 days, the death rate was 100% in newborns, 25% in 27-day-old rats, and 0% in 44- to 96-day-old rats. Death occurred when lung water was > 84% except in newborns, which tolerated high lung water for the first 7 days. In chronically exposed 44- and 96-day-old rats, lung water returned to normal. Enzyme activity increased with O2 at all ages but did not relate to survival. In 96-day-old rats, the initial increase was suppressed on day 3. All chronically O2-exposed rats had minimal nonvascular parenchymal changes but developed right ventricular hypertrophy and increased alveolar ductal artery muscularization and lost alveolar capillaries. The most mature rats were least affected. In O2, there was pulmonary insufficiency the first 3 days, followed by recovery, and later hypercarbia and decreased arterial PO2. We conclude that young rats, 0-44 days old, are more O2 tolerant for 5 days. More mature animals, surviving 5 days, are more tolerant to chronic exposure.
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PMID:Comparative age-related acute and chronic pulmonary oxygen tolerance in rats. 789 11

Oxygen toxicity is attributed to the reaction of oxygen metabolites with cellular components leading to cell destruction. Activation of latent human neutrophil interstitial collagenase by reactive oxygen species has been demonstrated. The potential role of collagenases in hyperoxic lung injury has not been investigated. We studied the effect of hyperoxia on newborn rat lung water content, morphology and ultrastructure, interstitial (type I) and type IV collagenase gene expression and type I and IV collagenolytic activity. We observed that hyperoxia causes pulmonary edema, alters newborn rat lung morphology in a sequential manner and produces ultrastructural alterations, induces type I and increases type IV collagenase mRNA expression, and increases type I and IV collagenolytic activity. A role for type I and IV collagenase in hyperoxic newborn lung injury or in the recovery following the injury is proposed.
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PMID:Hyperoxia induces interstitial (type I) and increases type IV collagenase mRNA expression and increases type I and IV collagenolytic activity in newborn rat lung. 799 51

In newborn rats, antenatal thyroid stimulation with thyroid-releasing hormone is associated with developmental decreases in pulmonary antioxidant enzyme activities and decreased survival rates during prolonged hyperoxic exposure, with pathologic evidence of increased O2-induced lung damage. Propylthiouracil (PTU), in addition to its antithyroid effects, reportedly has antioxidant properties. To explore possible pulmonary protective effects from both the antithyroid and antioxidant properties of PTU, we administered PTU (0.015%) in drinking water to timed-pregnant rats for the final 10 d of gestation and during lactation; control rats received untreated water. The survival rate of the PTU-treated pups when placed in more than 95% O2 at birth was consistently higher at all time periods in hyperoxia from 6 d [PTU, 81 of 81 (100%); control pups, 70 of 84 (83%); p < 0.01] to 14 d [PTU, 41 of 53 (77%); control pups = 14 of 56 (25%); p < 0.01]. Further evidence of increased tolerance to more than 95% O2 in PTU pups included a significant decrease in the incidence of microscopic intraalveolar edema, decreased lipid peroxidation (malondialdehyde), and a significant increase in lung tissue surfactant-related phospholipids compared with O2-exposed control pups. No differences were present in lung structural maturation, antioxidant enzyme activity response to hyperoxia, or lung tissue O2 radical formation in more than 95% O2. We conclude that PTU treatment has important postnatal effects that protect newborn rats against oxidant-induced lung injury and lethality during hyperoxia, which may be related to PTU inhibition of thyroid hormone production, effect on O2 metabolism, or its direct antioxidant properties.
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PMID:Propylthiouracil treatment decreases the susceptibility to oxygen radical-induced lung damage in newborn rats exposed to prolonged hyperoxia. 806 33

Experiments were performed to determine whether T2* and resonance frequency weighted MR images are sensitive to effects of hyperoxia on model tumors. Hyperoxia can increase tumor oxygen tension and thus affect T2* and/or the average resonance frequency within each image voxel due to the paramagnetism of oxygen itself or through modulation of the oxidation state of hemoglobin. Alternatively, changes in T2* during hyperoxia may reflect changes in tumor water content due to changes in systemic blood pressure. Mammary adenocarcinomas implanted in the flanks of rats were studied. Imaging sequences were preceded by two 90 degrees pulses separated by an evolution period of 50 or 75 ms and followed by a crusher gradient to eliminate transverse magnetization. This pulse sequence produced images which were sensitized to both T2* and the average resonance frequency of each voxel. Images were produced at 2 T using a gradient echo imaging method with a TR of 3 s. Images obtained during inhalation of air and 100% O2 were compared. Significant increases in image intensity were observed in most tumors during hyperoxia, particularly at the tumor center. The increase was accentuated when the evolution period was increased and greatly reduced when a 180 degrees refocusing pulse was placed at the center of the evolution period. These results suggest that hyperoxia reduces local magnetic susceptibility gradients leading to an increase in T2* or causes a shift in resonance frequency. The magnitude of this change may be a function of the rate at which oxygen is delivered to and metabolized by tumors and may also reflect tumor oxygen tension under normoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of hyperoxia on T2* and resonance frequency weighted magnetic resonance images of rodent tumours. 806 23

Deep saturation diving has been shown to have prolonged effects on pulmonary function. We wanted to assess the relative contribution of various factors that could contribute to these effects. Pulmonary function was, therefore, measured before and after 17 different saturation diving operations to depths of 5-450 m of sea water, corresponding to absolute pressures of 0.15-4.6 MPa. Four to fifteen divers participated in each operation. The measurements included static and dynamic lung volumes and flows, transfer factor of the lungs for carbon monoxide (TLCO), and closing volume. The dives were characterized by the cumulative hyperoxic and hyperbaric exposures, and the load of venous gas microemboli encountered during decompression was measured in 41 divers in three dives to 0.25, 1.2 and 3.7 MPa. TLCO was reduced by 8.3 +/- 7.0% mean +/- SD after the dives, this correlated with cumulative hyperoxic exposure and load of venous gas microembolism, independently of each other. Closing volume was increased and forced mid-expiratory flow rate reduced, in correlation with cumulative hyperoxic exposure. An increase in total lung capacity correlated with cumulative hyperbaric exposure. We conclude that hyperoxia, hyperbaria, and venous gas microembolism all contribute to the changes in pulmonary function after a single saturation dive, and all may explain some of the long-term effects of diving on pulmonary function.
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PMID:Mechanisms of reduced pulmonary function after a saturation dive. 814 30

We investigated the effects of lung edema protein on ventilatory mechanics with special reference to surfactant activity. The edema fluid was obtained from hyperoxia-exposed adult rabbits. In immature newborn rabbits that could not be artificially ventilated at an insufflation pressure of 25 cm H2O, mean tidal volumes of > 27 ml/kg were obtained by supplementation with a natural surfactant (S-alone) or natural surfactant mixed with lung edema fluid (EF), the edema protein-to-surfactant ratio of which was < or = 5.6. A mixture with a ratio of 11.2 (11.2-EF/S), however, decreased the volume to 10.9 ml/kg (P < 0.05 vs S-alone). Surfactant mixed with isolated albumin at a concentration equal to that in 11.2-EF/S decreased the tidal volume to 8.6 ml/kg (NS vs 11.2-EF/S), and with isolated fibrinogen lowered it to 18.1 mg/kg (P < 0.05 vs S-alone). We conclude that lung edema fluid impairs ventilation through surfactant inactivation when the protein-to-surfactant ratio increases, and that albumin and fibrinogen are the main causes of this impairment.
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PMID:Impairment of surfactant activity and ventilation by proteins in lung edema fluid. 815 52

An animal model of oxygen-induced pulmonary injury was used to assess the potential of contrast-enhanced MRI to identify and quantify abnormal capillary permeability. Sprague-Dawley rats were exposed to 100% oxygen for 48 h (n = 5) or 60 h (n = 9). Axial spin-echo MR images were acquired in intubated, anesthetized rats with ECG-gating (TR 400; TE 6) immediately or 7 days after the cessation of oxygen exposure. Polylysine-Gd-DTPA, a macromolecular paramagnetic blood-pool marker, was then given intravenously and the lungs were serially imaged for 42 to 47 min to monitor changes in signal intensity. Pulmonary enhancement was stable in rats exposed to 48 h of oxygen, and in rats exposed to 60 h of oxygen and given 7 days to recover. However, animals exposed to 100% oxygen for 60 h without a period of recovery showed a progressive increase in lung signal intensity for 15 min after polylysine-Gd-DTPA. Pleural effusions also showed progressively increasing signal, reflecting a capillary endothelial leak. A two compartment model describing the kinetics of polylysine-Gd-DTPA in the plasma and interstitial water of the lung was consistent with the dynamic MRI data and allowed estimation of the fractional leak rate (0.235 min-1) of the contrast agent from plasma to interstitial water. Given the assumption of our kinetic model, MRI following intravenous administration of polylysine-Gd-DTPA can be used to quantitate changes in capillary integrity induced by hyperoxia, including acute capillary leakiness and return to normal endothelial integrity with recovery from hyperoxic injury.
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PMID:Pulmonary oxygen toxicity: demonstration of abnormal capillary permeability using contrast-enhanced MRI. 830 47

To examine the potential impact of fluid dynamic boundary layers on cutaneous ion exchange, we investigated how bulk flow of dilute Na+ solutions (< or = 1.0 mmol l-1) over the skin of intact frogs (Rana catesbeiana and Rana pipiens) affects cutaneous Na+ uptake (JNa(in)) and transepithelial potential (TEP). Cessation of stirring resulted in a 14-35% decrease in TEP and a 14-65% decrease in JNa(in). Two weeks' acclimation to an unstirred bath increased JNa(in) to levels 70% greater than in frogs acclimated to a continuously stirred bath and to levels comparable to those of frogs acclimated to deionized water. These effects are consistent with depletion of Na+ in the boundary layer, but are also consistent with depletion of O2 in the boundary layer, which might limit generation of ATP consumed by ATPases responsible for cutaneous Na+ uptake. To investigate this latter possibility, we measured TEP and JNa(in) while manipulating the PO2 of well-stirred external media at constant [Na+]. Hyperoxia (PO2 > or = 97 kPa) increased JNa(in) by 28% and had little or no effect on TEP. Hypoxia (PO2 < or = 1.5 kPa) reduced JNa(in) by 48% and decreased TEP by 22%. These results suggest that ionic and gaseous boundary layers may interact to affect cutaneous ion transport.
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PMID:Bulk flow of the medium and cutaneous sodium uptake in frogs: potential significance of sodium and oxygen boundary layers. 844 Sep 67


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