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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Anesthesia & Analgesia Vol. 112, No. 1 ( 2011-01), p. 143-149
    In: Anesthesia & Analgesia, Ovid Technologies (Wolters Kluwer Health), Vol. 112, No. 1 ( 2011-01), p. 143-149
    Type of Medium: Online Resource
    ISSN: 0003-2999
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 2018275-2
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  • 2
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 113, No. 5 ( 2004-05-01), p. 1267-1272
    Abstract: Objective. Active ion transport is critical to postnatal clearance of lung fluid. The importance of epithelial sodium channel (ENaC) in this clearance has been demonstrated in animal studies in which α-ENaC knockout mice died postnatally as a result of respiratory insufficiency. In animals, the expression of α-ENaC in respiratory epithelium is dependent on gestational age, but when assessed by in situ hybridization in the human (h), the mRNA is present from the earliest stages of pulmonary development. Therefore, the purpose of the present investigation was to quantify mRNA of the α-, β-, and γ-hENaC subunits of newborn preterm infants with respiratory distress and compare the gene expression data against those detected in healthy term infants. In addition, the effect of systemic dexamethasone therapy on the 3 hENaC subunits was studied in 4 preterm infants who received prolonged assisted ventilation. Methods. The expression of subunits of hENaC was determined in samples taken from nasal respiratory epithelium of 7 healthy term infants (gestation age: 39.3 ± 0.9 weeks [mean ± standard deviation) and 5 preterm infants (gestational age: 27.2 ± 0.9 weeks) with respiratory distress syndrome within 5 hours of birth. Betamethasone had been given to all mothers of preterm infants. In 4 additional preterm infants who still required assisted ventilation at 43 ± 6 days postnatal age, the expression of α-hENaC was determined in samples taken before and during treatment with dexamethasone. Results. Preterm infants with respiratory distress syndrome had low expression of all hENaC subunits relative to healthy term infants (α-hENaC: 5.38 ± 2.01 [amol/fmol cytokeratin 18] vs 9.13 ± 2.26; β-hENaC: 2.44 ± 1.43 vs 4.25 ± 1.10; γ-hENaC: 2.43 ± 0.11 vs 6.81 ± 3.24). Each of the 4 preterm infants who were treated with dexamethasone at ∼1 month of age showed an increase in expression of α-hENaC and β-hENaC subunit normalized to cytokeratin 18. Conclusion. All 3 subunits of the hENaC are low in preterm relative to full-term infants. α-hENaC mRNA in respiratory epithelium is increased by therapeutic doses of glucocorticosteroid. Low expression of α-hENaC in human respiratory epithelium may play a role in the pathogenesis of respiratory distress in preterm infants.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2004
    detail.hit.zdb_id: 1477004-0
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  • 3
    Online Resource
    Online Resource
    Canadian Science Publishing ; 1989
    In:  Genome Vol. 31, No. 1 ( 1989-01-01), p. 435-436
    In: Genome, Canadian Science Publishing, Vol. 31, No. 1 ( 1989-01-01), p. 435-436
    Type of Medium: Online Resource
    ISSN: 0831-2796 , 1480-3321
    Language: English
    Publisher: Canadian Science Publishing
    Publication Date: 1989
    detail.hit.zdb_id: 2020635-5
    SSG: 12
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  • 4
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 5 ( 2022-05-01), p. 779-791
    Abstract: Vigorous spontaneous effort can potentially worsen lung injury. This study hypothesized that the prone position would diminish a maldistribution of lung stress and inflation after diaphragmatic contraction and reduce spontaneous effort, resulting in less lung injury. Methods A severe acute respiratory distress syndrome model was established by depleting surfactant and injurious mechanical ventilation in 6 male pigs (“mechanism” protocol) and 12 male rabbits (“lung injury” protocol). In the mechanism protocol, regional inspiratory negative pleural pressure swing (intrabronchial balloon manometry) and the corresponding lung inflation (electrical impedance tomography) were measured with a combination of position (supine or prone) and positive end-expiratory pressure (high or low) matching the intensity of spontaneous effort. In the lung injury protocol, the intensities of spontaneous effort (esophageal manometry) and regional lung injury were compared in the supine position versus prone position. Results The mechanism protocol (pigs) found that in the prone position, there was no ventral-to-dorsal gradient in negative pleural pressure swing after diaphragmatic contraction, irrespective of the positive end-expiratory pressure level (–10.3 ± 3.3 cm H2O vs. –11.7 ± 2.4 cm H2O at low positive end-expiratory pressure, P = 0.115; –10.4 ± 3.4 cm H2O vs. –10.8 ± 2.3 cm H2O at high positive end-expiratory pressure, P = 0.715), achieving homogeneous inflation. In the supine position, however, spontaneous effort during low positive end-expiratory pressure had the largest ventral-to-dorsal gradient in negative pleural pressure swing (–9.8 ± 2.9 cm H2O vs. –18.1 ± 4.0 cm H2O, P & lt; 0.001), causing dorsal overdistension. Higher positive end-expiratory pressure in the supine position reduced a ventral-to-dorsal gradient in negative pleural pressure swing, but it remained (–9.9 ± 2.8 cm H2O vs. –13.3 ± 2.3 cm H2O, P & lt; 0.001). The lung injury protocol (rabbits) found that in the prone position, spontaneous effort was milder and lung injury was less without regional difference (lung myeloperoxidase activity in ventral vs. dorsal lung, 74.0 ± 30.9 μm · min–1 · mg–1 protein vs. 61.0 ± 23.0 μm · min–1 · mg–1 protein, P = 0.951). In the supine position, stronger spontaneous effort increased dorsal lung injury (lung myeloperoxidase activity in ventral vs. dorsal lung, 67.5 ± 38.1 μm · min–1 · mg–1 protein vs. 167.7 ± 65.5 μm · min–1 · mg–1 protein, P = 0.003). Conclusions Prone position, independent of positive end-expiratory pressure levels, diminishes a maldistribution of lung stress and inflation imposed by spontaneous effort and mitigates spontaneous effort, resulting in less effort-dependent lung injury. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
    Type of Medium: Online Resource
    ISSN: 0003-3022 , 1528-1175
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2016092-6
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  • 5
    Online Resource
    Online Resource
    American Physiological Society ; 2011
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 300, No. 4 ( 2011-04), p. L648-L658
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 300, No. 4 ( 2011-04), p. L648-L658
    Abstract: Ventilator-induced lung injury (VILI) due to high tidal volume (V T ) is associated with increased levels of circulating factors that may contribute to, or be markers of, injury. This study investigated if exclusively lung-derived circulating factors produced during high V T ventilation can cause or worsen VILI. In isolated perfused mouse lungs, recirculation of perfusate worsened injury (compliance impairment, microvascular permeability, edema) induced by high V T . Perfusate collected from lungs ventilated with high V T and used to perfuse lungs ventilated with low V T caused similar compliance impairment and permeability and caused a dose-dependent decrease in transepithelial electrical resistance (TER) across rat distal lung epithelial monolayers. Circulating soluble factors derived from the isolated lung thus contributed to VILI and had deleterious effects on the lung epithelial barrier. These data demonstrate transferability of an injury initially caused exclusively by mechanical ventilation and provides novel evidence for the biotrauma hypothesis in VILI. Mediators of the TER decrease were heat-sensitive, transferable via Folch extraction, and (following ultrafiltration, 3 kDa) comprised both smaller and larger molecules. Although several classes of candidate mediators, including protein cytokines (e.g., tumor necrosis factor-α, interleukin-6, macrophage inflammation protein-1α) and lipids (e.g., eicosanoids, ceramides, sphingolipids), have been implicated in VILI, only prostanoids accumulated in the perfusate in a pattern consistent with a pathogenic role, yet cyclooxygenase inhibition did not protect against injury. Although no single class of factor appears solely responsible for the decrease in barrier function, the current data implicate lipid-soluble protein-bound molecules as not just markers but pathogenic mediators in VILI.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2011
    detail.hit.zdb_id: 1477300-4
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Critical Care Medicine Vol. 41, No. 1 ( 2013-01), p. 151-158
    In: Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 1 ( 2013-01), p. 151-158
    Type of Medium: Online Resource
    ISSN: 0090-3493
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2034247-0
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  • 7
    Online Resource
    Online Resource
    American Physiological Society ; 2019
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 316, No. 1 ( 2019-01-01), p. L1-L5
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 316, No. 1 ( 2019-01-01), p. L1-L5
    Abstract: Vitamin E (VitE) has important antioxidant and anti-inflammatory effects and is necessary for normal physiological function. α-Tocopherol (α-T), the predominant form of VitE in human tissues, has been extensively studied. Other VitE forms, particularly γ-tocopherol (γ-T), are also potent bioactive molecules. The effects are complex, involving both reactive oxygen and nitrogen species, but trials of VitE have been generally negative. We propose that a nanoparticle approach to delivery of VitE might provide effective delivery and therapeutic effect.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2019
    detail.hit.zdb_id: 1477300-4
    SSG: 12
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  • 8
    In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 205, No. 6 ( 2022-03-15), p. 663-673
    Type of Medium: Online Resource
    ISSN: 1073-449X , 1535-4970
    RVK:
    Language: English
    Publisher: American Thoracic Society
    Publication Date: 2022
    detail.hit.zdb_id: 1468352-0
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  • 9
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 6 ( 2019-06-13), p. 847-
    Abstract: Enhancing the immunomodulatory effects of mesenchymal stromal cells (MSCs) may increase their effects in sepsis. We tested the potential for overexpression of Interleukin-10 (IL-10) in human umbilical cord (UC) MSCs to increase MSC efficacy in Escherichia coli (E. coli) pneumosepsis and to enhance human macrophage function. Pneumonia was induced in rats by intratracheal instillation of E. coli ((2.0–3.0) × 109 Colony forming units (CFU)/kg). One hour later, animals were randomized to receive (a) vehicle; (b) naïve UC-MSCs; or (c) IL-10 overexpressing UC-MSCs (1 × 107 cells/kg). Lung injury severity, cellular infiltration, and E. coli colony counts were assessed after 48 h. The effects and mechanisms of action of IL-10 UC-MSCs on macrophage function in septic rodents and in humans were subsequently assessed. Survival increased with IL-10 (9/11 (82%)) and naïve (11/12 (91%)) UC-MSCs compared to vehicle (9/15 (60%, p = 0.03). IL-10 UC-MSCs—but not naïve UC-MSCs—significantly decreased the alveolar arterial gradient (455 ± 93 and 520 ± 81, mmHg, respectively) compared to that of vehicle animals (544 ± 52, p = 0.02). Lung tissue bacterial counts were significantly increased in vehicle- and naïve-UC-MSC-treated animals but were not different from sham animals in those treated with IL-10 overexpressing UC-MSCs. IL-10 (but not naïve) UC-MSCs decreased alveolar neutrophils and increased alveolar macrophage percentages compared to vehicle. IL-10 UC-MSCs decreased structural lung injury compared to naïve UC-MSC or vehicle therapy. Alveolar macrophages from IL-10-UC-MSC-treated rats and from human volunteers demonstrated enhanced phagocytic capacity. This was mediated via increased macrophage hemeoxygenase-1, an effect blocked by prostaglandin E2 and lipoxygenase A4 blockade. IL-10 overexpression in UC-MSCs enhanced their effects in E. coli pneumosepsis and increased macrophage function. IL-10 UC-MSCs similarly enhanced human macrophage function, illustrating their therapeutic potential for infection-induced acute respiratory distress syndrome (ARDS).
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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  • 10
    Online Resource
    Online Resource
    American Thoracic Society ; 2017
    In:  American Journal of Respiratory and Critical Care Medicine Vol. 196, No. 11 ( 2017-12-01), p. 1411-1421
    In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 196, No. 11 ( 2017-12-01), p. 1411-1421
    Type of Medium: Online Resource
    ISSN: 1073-449X , 1535-4970
    RVK:
    Language: English
    Publisher: American Thoracic Society
    Publication Date: 2017
    detail.hit.zdb_id: 1468352-0
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