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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperoxia has been reported to stimulate both resorption and synthesis of bone in vitro. The effects of increased oxygen tension were re-investigated using calvaria from infant mice maintained in a stationary grid culture system for 48 48 hours with an unsupplemented chemically defined medium. Resting resorption due to osteoclastic activity was demonstrated in the explants in air by Von Kossa staining, histology, and 45 Ca release. Resorption was inhibited by exposure to 95 per cent oxygen or hyperbaric oxygenation at 2 atmospheres pressure. Hyperoxia also depressed new bone formatin by osteoblasts although the production of a new collagen, as measured by the incorporation of 3H-proline, was greater in calvaria cultured in hyperbaric oxygen than in paired explants in 95 per cent oxygen. Thus hyperoxia was toxic for both synthetic and resorptive activity of bone cells; these effects may stem from the loss of vital factors present in natural MEDIA supplements.
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PMID:The effects of hyperoxia upon bone in organ culture. 95 15

Although direct intercellular contacts between alveolar epithelial cells and fibroblasts have been described in developing and adult lung, the frequency of such contacts and their relationship to type 2 cell division and differentiation in normal and abnormal repair is not known. The authors now correlate measurements of type 2 cell basal surface, basement membrane continuity, and the incidence of epithelial-interstitial cell contacts with the proliferative index of type 2 cells and fibroblasts in normal repair (after hyperoxia) and in abnormal repair with fibrosis (after bleomycin or butylated hydroxytoluene). In each case, type 1 cell necrosis was followed by an increase in type 2 cell basal surface as the cells spread over the denuded capillary wall before dividing. After hyperoxia, a high but short-lived peak in type 2 cell division was not accompanied by fibrosis. After more severe drug-induced injury, the type 2 proliferative phase was extended and was accompanied by prolonged fibroblast growth. Type 2 cells persisted where they covered a thick interstitium of fibroblasts and fibrillar collagen. The incidence of epithelial-interstitial cell contacts decreased at the time of maximal type 2 cell division, then increased immediately after the peak. The results suggest a reciprocal epithelial-fibroblast control system whereby 1) epithelial necrosis and delayed repair promotes fibroblast growth, and 2) direct contact of epithelial cells with fibroblasts or fibrillar collagen may provide a factor important for the regulation of type 2 cell growth and differentiation.
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PMID:Epithelial cell-fibroblast interactions in lung injury and repair. 169 85

Confluent calf pulmonary artery endothelial monolayers exposed to 95% oxygen for 1, 2, or 3 days exhibit a time-dependent increase in adherence to substratum, which closely parallels changes in actin cytoarchitecture and the distribution of focal contact proteins vinculin and talin. Oxygen exposure also resulted in elevated plasminogen activator (PA) activity in conditioned media (CM) and in cytoskeletal protein- and focal contact protein-enriched fractions, with highest levels achieved in the latter two fractions at 48 h after oxygen exposure. PAs have been shown to participate in dismantling of extracellular matrix in a number of physiological and pathological situations. Immunocytochemical studies demonstrated extensive restructuring of matrix proteins collagen IV, laminin, and fibronectin, which correlated temporally with elevated PA levels. Further, when protease-containing cell fractions were used to study degradation of isolated matrices, those obtained from hyperoxia-exposed cells were substantially more active than those from normoxia-exposed cells. Our data suggest that hyperoxia-induced production of PA (and perhaps other proteases) may be partly responsible for degradation of the extracellular matrix of endothelial cells.
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PMID:Hyperoxia increases plasminogen activator activity of cultured endothelial cells. 173 78

Neonatal rats usually lose their marked tolerance to hyperoxia at about 1 mo of age. We examined the hypothesis that the marked dietary change that occurs at weaning might be important to this loss of O2 tolerance. We, therefore, prematurely weaned rat pups at 15-17 d of age, expecting to find an earlier loss of O2 tolerance. Surprisingly, the prematurely weaned rats showed consistently prolonged relative O2 tolerance compared with normally weaned rats at all ages tested from 35-85 d of life. For example, when challenged with greater than 95% O2 exposure for 7 d, the composite survival rate of the prematurely weaned rats (at 35-85 d of age) was nearly twice that of the normally weaned group (83 of 107 = 78% versus 44 of 107 = 41%, p less than 0.01). In the two experimental groups, nearly all comparative parameters examined were similar, including: 1) growth rate; 2) lung DNA, RNA, and protein; 3) lung antioxidant enzymes and enzyme responses to hyperoxia; 4) lung morphometry; and 5) lung elastin and collagen content. Only serum corticosterone and triiodothyronine levels differed considerably in the two groups. We conclude that premature weaning has a very marked and sustained positive effect on the relative retention of O2 tolerance in the growing rat.
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PMID:Premature weaning of rat pups results in prolongation of neonatal tolerance to hyperoxia. 185 32

Bleomycin is a commonly used antineoplastic agent which produces dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced lung injury is uncertain. However, current data shows that bleomycin can generate reactive oxygen species such as superoxide and hydroxyl radicals. We therefore investigated whether intraperitoneal (i.p.) injection of endotoxin, a protectant for hyperoxia, could modulate the biochemical and morphological estimates of bleomycin-induced lung fibrosis in rats. However, pretreatment with multiple i.p. injections of endotoxin, combined with intratracheal bleomycin instillation, resulted in increased lung collagen content compared to bleomycin treatment alone and controls. Furthermore, morphological estimates of the severity of lung lesions present in the endotoxin-bleomycin treatment group were increased when compared with saline and endotoxin control lung lesions. These data indicate, in the current study design, that endotoxin did not reduce, but instead increased the severity of bleomycin-induced pulmonary fibrosis in rats. The mechanism for this increase in fibrosis may be the result of pre-existing endotoxin-induced cell injury.
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PMID:The effect of endotoxin on bleomycin-induced lung fibrosis in the rat. 241 66

The concomitant treatment of rats with bleomycin and hyperoxia results in synergistic development of pulmonary injury. We exposed rats to 70% oxygen for 72 hr following an intratracheal instillation of bleomycin (0.2 U/kg body wt). Animals were killed 15, 30, 60 and 90 days after treatment for hydroxyproline, cell kinetics, and histopathologic analysis. A 16% increase in hydroxyproline over controls was seen 15 days after treatment which was manifested by the proliferation phase of diffuse alveolar damage and an increase in cell labeling by tritiated thymidine. Thirty days after treatment the hydroxyproline remained elevated while lung injury appeared to be healing with a residual focal interstitial pneumonitis and a drop in cell labeling. Between 60 and 90 days, there was an additional significant increase in hydroxyproline to 44% over controls. Diffuse interstitial pneumonitis with fibrosis was observed. Cell labeling remained constant between 60 and 90 days. We conclude that the treatment of rats with bleomycin and hyperoxia results in slowly progressive pulmonary fibrosis. The increase in hydroxyproline in the chronic phase was not accompanied by an increase in cell proliferation, and therefore may have resulted from an increase in cellular production of hydroxyproline rather than increased number of cells producing collagen.
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PMID:Progressive pulmonary fibrosis in rats: a biochemical, cell kinetic, and morphologic analysis. 241 89

Rats were treated with subcutaneous injections of either saline or 1, 3, or 5 units of bleomycin (BLM) each day for 5 days (5, 15, or 25 units total dose). One half of each group of animals was exposed to 80% oxygen for 4 days during BLM dosings. Rats treated with both 25 units BLM and hyperoxia died after being returned to room air. All remaining rats were sacrificed 6 weeks following the end of treatment. Of the BLM rats in room air, only the lungs of the 15-unit group exhibited histological change, a mild diffuse interstitial disease. Both lower dose groups demonstrated slight increases in hydroxy-proline (OHP) content, a marker of collagen deposition or lung injury. The lungs of BLM rats exposed to hyperoxia demonstrated greater increases in total lung OHP levels. The lungs of the 15-unit group demonstrated lesions consistent with diffuse interstitial pulmonary fibrosis. Short-term, sublethal hyperoxia clearly potentiated injury in the rat following subcutaneous BLM treatment as assessed by either lethality or markers of pulmonary pathology.
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PMID:Non-lethal hyperoxic potentiation of lung disease in the rat following subcutaneous administration of bleomycin. 246 89

Injury to the capillary endothelium and to alveolar epithelial cells of the lung may result in damage to the underlying collagen of the extracellular matrix. To examine this possibility, whole body irradiation, bleomycin injections, and exposure to hyperoxia were used to induce various types of lung damage in mice. The morphology of the lung and the cellular and protein content of bronchoalveolar lavage fluid were used to assess injury. Collagen breakdown was assessed from the hydroxyproline concentrations in bronchoalveolar lavage fluid. When lung cell injury was observed, protein leaked in to alveoli and hydroxyproline was detected in bronchoalveolar lavage fluid. An increase in hydroxyproline followed endothelial damage by irradiation and was greatly increased when type 1 epithelial cell necrosis also occurred after bleomycin injection or hyperoxia. Maximal concentrations of hydroxyproline occurred in mice showing respiratory distress after six days of hyperoxia. Concentrations returned to zero during the subsequent phases of cell regeneration and fibrosis seen after bleomycin injection and irradiation. There was little change in the cellular components of bronchoalveolar lavage fluid at any time. The results indicate that collagen breakdown occurs during acute lung injury and can be quantified in terms of the hydroxyproline concentration in lavage fluid. Such a change in the extracellular matrix might influence the subsequent division and differentiation of regenerating cells during repair.
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PMID:Collagen breakdown during acute lung injury. 246 95

Changes in lung structure and collagen metabolism were studied at 1, 2, 3, 4, 6, and 8 weeks in a model of pulmonary fibrosis induced in rats with paraquat plus hyperoxia. Morphologic examination of the lungs revealed that the earliest lesions consisted of severe and irreversible endothelial and alveolar epithelial cell damage. Afterward, an inflammatory process took place, initially dominated by polymorphonuclear leukocytes and then by mononuclear cells, but with the constant presence of granulocytes. From the fourth week on there were fibroblast proliferation and a moderate increase of mast cells. In the early stages alveolitis was focal, but from the second week the lungs were diffusely affected with severe distortion of the architecture. Collagen content was moderately increased in the first 2 weeks and then showed a progressive increment until the end of the experiment. Collagen synthesis was significantly elevated from the fourth week, coinciding with interstitial fibroblast proliferation, although there were some animals that showed increased collagen production from the first week. Collagenolytic activity occurred in 3 stages: at 2 weeks there was increased collagen degradation, at 3, 4, and 6 weeks the values showed a trimodal behavior, and at 8 weeks almost all experimental rats presented an important decrease of collagenolysis. Thus, the development of lung fibrosis was associated first with increased rates of collagen synthesis and later with a decrease of collagen degradation.
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PMID:Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study. 270 80

Neonatal lung injury from hyperoxia and mechanical hyperventilation was studied in newborn piglets hyperventilated (arterial PCO2 15-20 Torr) for 24-48 h with 100% O2 and compared with unventilated controls. Pulmonary function testing was performed, and biochemical indicators of lung injury were analyzed from tracheobronchial aspirates at 0, 24, and 48 h. Lung sections were obtained for light and electron microscopy, and bronchoalveolar lavage fluid was analyzed for surfactant composition and activity. At 24 h significant changes in tracheobronchial aspirate albumin concentrations (up 78%) and percent of polymorphonuclear cells (up 16%) were demonstrated. At 48 h a 35% decrease in dynamic lung compliance (P less than 0.05) and a 36% increase in pulmonary resistance (P less than 0.05) were noted. Further biochemical abnormalities occurred with total cell counts increased by 271% (P less than 0.02), albumin 163% (P less than 0.05), total protein 217% (P less than 0.01), and elastase 108% (P less than 0.02). Pathological analyses revealed mild lung injury at 24 h and marked inflammation, abnormal inflation patterns, flattening of Clara cells, fibrinous exudate and edema, early collagen formation, and cell necrosis observed at 48 h. Bronchoalveolar lavage surfactant had normal biophysical activity. Results demonstrate that exposure of neonatal piglets to O2 and mechanical hyperventilation for 48 h cause severe progressive lung injury.
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PMID:Lung injury in the neonatal piglet caused by hyperoxia and mechanical ventilation. 279 94


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