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Sample records for acute lung function

  1. Lung function

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005200 The effect of body position changes on lung function, lung CT imaging and pathology in an oleic acid induced acute lung injury model. JI Xin-ping (戢新平), et al. Dept Emergency, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Tuberc Respir Dis, 2005;28(1) :33-36. Objective: To study the effect of body position changes on lung mechanics, oxygenation, CT images and pathology in an oleic acid-induced acute lung injury (ALl) model. Methods: The study groups con-

  2. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

    Science.gov (United States)

    Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

    2015-02-01

    We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

  3. Acute morphine treatment alters cellular immune function in the lungs of healthy rats.

    Science.gov (United States)

    Coussons-Read, M E; Giese, S

    2001-08-01

    Previous work has shown that morphine suppresses the pulmonary immune response to infection and reduces pulmonary inflammation. No published studies have addressed the impact of morphine on lymphocyte function in the lungs without infection. This study addressed this question by assessing the impact of acute morphine treatment on proliferation, cytokine production, and natural killer (NK) cell activity in resident pulmonary lymphocytes from healthy rats. Male Lewis rats received either a single 15 mg/kg morphine sulfate or vehicle injection 1 h prior to sacrifice. Lungs were minced and passed through wire mesh following collagenase digestion. The resulting cell preparations were pooled (2 rats/pool) to yield sufficient cell numbers for the functional assays, and a portion of these suspensions were separated using a density gradient. Crude and purified cell suspensions were used in assays of NK cell activity and mitogen-induced proliferation and cytokine production. Morphine significantly suppressed lymphocyte proliferation and cytokine production in whole cell suspensions, but not in purified cultures. NK activity was enhanced by morphine treatment in purified treated cultures. Studies of nitrate/nitrite levels in crude and purified cultures suggest that macrophage-derived nitric oxide may be a mechanism of the suppression observed in whole cell suspensions following morphine treatment. These data are consistent with previous work showing that morphine suppresses mitogenic responsiveness and NK activity in the spleen and peripheral blood, and may do so through a macrophage-derived nitric oxide mechanism.

  4. Lung function in patients with acute exacerbation and stable COPD and its correlation with serum proinflammatory cytokines and chemokines

    Institute of Scientific and Technical Information of China (English)

    Xin-Jie Wang

    2016-01-01

    Objective:To analyze the lung function in patients with acute exacerbation and stable COPD and its correlation with serum proinflammatory factors and chemokines.Methods:A total of 87 patients with chronic obstructive pulmonary disease (COPD) were divided into observation group (n=32) at acute exacerbation phase and control group (n=55) at stable phase according to the illness. Differences in lung function indexes and serum levels of proinflammatory cytokines, chemokines were compared between two groups of patients, and the correlation between lung function indexes and serum levels of proinflammatory cytokines and chemokines was further analyzed.Results: FEV1, FVC, FEV1/FVC, FEF75, PEF and IC levels of observation group were significantly lower than those of control group; serum proinflammatory cytokines IL-1β, IL-4, IL-18, IL-23, TNF-α and IFN-γ content were significantly higher than those of control group; serum chemokines Eotaxin, MDC, FKN, MCP-1, CCL18 and RANTES content were significantly higher than those of control group. FEV1, FVC and FEV1/FVC levels in patients with COPD were negatively correlated with the content of proinflammatory cytokines and chemokines.Conclusions: Lung function declines in acute exacerbation COPD, and the changes in levels of both proinflammatory cytokines and chemokines are involved in it.

  5. Long-term effects of severe acute malnutrition on lung function in Malawian children: a cohort study.

    Science.gov (United States)

    Lelijveld, Natasha; Kerac, Marko; Seal, Andrew; Chimwezi, Emmanuel; Wells, Jonathan C; Heyderman, Robert S; Nyirenda, Moffat J; Stocks, Janet; Kirkby, Jane

    2017-04-01

    Early nutritional insults may increase risk of adult lung disease. We aimed to quantify the impact of severe acute malnutrition (SAM) on spirometric outcomes 7 years post-treatment and explore predictors of impaired lung function.Spirometry and pulse oximetry were assessed in 237 Malawian children (median age: 9.3 years) who had been treated for SAM and compared with sibling and age/sex-matched community controls. Spirometry results were expressed as z-scores based on Global Lung Function Initiative reference data for the African-American population.Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were low in all groups (mean FEV1 z-score: -0.47 for cases, -0.48 for siblings, -0.34 for community controls; mean FVC z-score: -0.32, -0.38, and -0.15 respectively). There were no differences in spirometric or oximetry outcomes between SAM survivors and controls. Leg length was shorter in SAM survivors but inter-group sitting heights were similar. HIV positive status or female sex was associated with poorer FEV1, by 0.55 and 0.31 z-scores, respectively.SAM in early childhood was not associated with subsequent reduced lung function compared to local controls. Preservation of sitting height and compromised leg length suggest "thrifty" or "lung-sparing" growth. Female sex and HIV positive status were identified as potentially high-risk groups.

  6. Biomarkers in acute lung injury.

    Science.gov (United States)

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.

  7. Effect of oleic acid-induced acute lung injury and conventional mechanical ventilation on renal function in piglets

    Institute of Scientific and Technical Information of China (English)

    LIU Ai-jun; LING Feng; LI Zhi-qiang; LI Xiao-feng; LIU Ying-long; DU Jie; HAN Ling

    2013-01-01

    Background Animal models that demonstrate changes of renal function in response to acute lung injury (ALl) and mechanical ventilation (MV) are few.The present study was performed to examine the effect of ALl induced by oleic acid (OA) in combination with conventional MV strategy on renal function in piglets.Methods Twelve Chinese mini-piglets were randomly divided into two groups:the OA group (n=6),animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALl induced by administration of OA,and the control group (n=6),animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of sterile saline.Results Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen,while no apparent histological abnormalities were observed in the control group.Although we observed an increase in the plasma concentrations of creatinine and urea after ALl,there was no significant difference compared with the control group.Plasma concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C increased (5.6±1.3) and (7.4±1.5) times in the OA group compared to baseline values,and were significantly higher than the values in the control group.OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters,while these parameters remained stable during the experiment in the control group.The plasma expression of TNF-α and IL-6 in the OA group were significantly higher than that in the control group.Compared with high expression in the lung and renal tissue in the OA group,TNF-α and IL-6 were too low to be detected in the lung and renal tissue in the control group.Conclusions OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury.The potential mechanisms involved a cytokine response of TNF-α and

  8. Identification of target proteins of mangiferin in mice with acute lung injury using functionalized magnetic microspheres based on click chemistry.

    Science.gov (United States)

    Wang, Jiajia; Nie, Yan; Li, Yunjuan; Hou, Yuanyuan; Zhao, Wei; Deng, Jiagang; Wang, Peng George; Bai, Gang

    2015-11-18

    Prevention of the occurrence and development of inflammation is a vital therapeutic strategy for treating acute lung injury (ALI). Increasing evidence has shown that a wealth of ingredients from natural foods and plants have potential anti-inflammatory activity. In the present study, mangiferin, a natural C-glucosyl xanthone that is primarily obtained from the peels and kernels of mango fruits and the bark of the Mangifera indica L. tree, alleviated the inflammatory responses in lipopolysaccharide (LPS)-induced ALI mice. Mangiferin-modified magnetic microspheres (MMs) were developed on the basis of click chemistry to capture the target proteins of mangiferin. Mass spectrometry and molecular docking identified 70 kDa heat-shock protein 5 (Hspa5) and tyrosine 3-monooxygenase (Ywhae) as mangiferin-binding proteins. Furthermore, an enzyme-linked immunosorbent assay (ELISA) indicated that mangiferin exerted its anti-inflammatory effect by binding Hspa5 and Ywhae to suppress downstream mitogen-activated protein kinase (MAPK) signaling pathways. Thoroughly revealing the mechanism and function of mangiferin will contribute to the development and utilization of agricultural resources from M. indica L.

  9. TNF-α mediated increase of HIF-1α inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI).

    Science.gov (United States)

    Tang, Mengjie; Tian, Yihao; Li, Doulin; Lv, Jiawei; Li, Qun; Kuang, Changchun; Hu, Pengchao; Wang, Ying; Wang, Jing; Su, Ke; Wei, Lei

    2014-01-01

    Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function and increased pulmonary vascular permeability. Vasodilator-stimulated phosphoprotein (VASP) is widely associated with all types of modulations of cytoskeleton rearrangement-dependent cellular morphology and function, such as adhesion, shrinkage, and permeability. The present studies were conducted to investigate the effects and mechanisms by which tumor necrosis factor-alpha (TNF-α) increases the tight junction permeability in lung tissue associated with acute lung inflammation. After incubating A549 cells for 24 hours with different concentrations (0-100 ng/mL) of TNF-α, 0.1 to 8 ng/mL TNF-α exhibited no significant effect on cell viability compared with the 0 ng/mL TNF-α group (control group). However, 10 ng/mL and 100 ng/mL TNF-α dramatically inhibited the viability of A549 cells compared with the control group (*pTNF-α for 24 hours displayed significantly increased cell permeability (*pinhibition of VASP expression increased the cell permeability (*pTNF-α in lung tissues and serum significantly increased at one hour, and the value reached a peak at four hours. Moreover, the Evans Blue absorption value of the mouse lung tissues reached a peak at four hours. The HIF-1α protein expression level in mouse lung tissues increased significantly at four hours and eight hours (**pTNF-α to inhibit VASP expression and to modulate the acute pulmonary inflammation process, and these molecules play an important role in the impairment of the alveolar-capillary barrier.

  10. Pathogenesis of acute lung injury in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    SHI Lei; YUE Yuan; ZHANG Mei; PAN Cheng-en

    2005-01-01

    Objective:To study the pathogenesis of acute lung injury in severe acute pancreatitis (SAP). Methods:Rats were sacrificed at 1, 3, 5, 6, 9 and 12 h after establishment of inducing model. Pancreas and lung tissues were obtained for pathological study, microvascular permeability and MPO examination. Gene expressions of TNF-α and ICAM-1 in pancreas and lung tissues were detected by RT-PCR. Results:After inducing SAP model, the injury degree of the pancreas and the lung increased gradually, accompanied with gradually increased MPO activity and microvascular permeability. Gene expressions of TNF-α and ICAM-1 in pancreas rose at 1 h and reached peak at 7 h. Relatively, their gene expressions in the lungs only rose slightly at 1 h and reached peak at 9-12 h gradually. Conclusion:There is an obvious time window between SAP and lung injury, when earlier protection is beneficial to prevent development of acute lung injury.

  11. Measurement of lung function in awake 2-4-year-old asthmatic children during methacholine challenge and acute asthma

    DEFF Research Database (Denmark)

    Klug, B; Bisgaard, H

    1996-01-01

    This study evaluated three techniques for testing of lung function in young awake children. We compared measurements by the forced or impulse oscillation technique (IOS), the interrupter technique (IT), and transcutaneous measurements of oxygen (tcPo2) with concomitant measurements of specific...

  12. ICAM-1 and Acute Pancreatitis Complicated by Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    XiPing Zhang

    2009-01-01

    Full Text Available One of the most common complications of acute pancreatitis is acute lung injury, during which intercellular adhesion molecule-1 (ICAM-1 plays an important role by participating in leukocyte adhesion and activation as well as by inducing the “cascade effect” of inflammatory mediators, pulmonary microcirculation dysfunction and even acute respiratory distress syndrome, multiple organ failure or death. Although it is generally believed that the modulatory mechanism of ICAM-1 during this process is associated with the activation of nuclear transcription factor kappa B which is mediated by IL-1, IL-6, IL-18 and oxygen free radical, etc., further studies are still required to clarify it. Since the upregulation of ICAM-1 expression in the lung during acute lung injury is one of main pathogeneses, the early detection of the ICAM-1 expression level may contribute to the prevention and treatment of acute lung injury. Moreover, reducing pulmonary ICAM-1 expression levels through treatment with anti-ICAM-1 monoclonal antibody (aICAM-1 and antagonists of the neurokinin 1 receptor, etc., should have a positive effect on protecting the lungs during acute pancreatitis. This review aims to further clarify the relationship between ICAM-1 and acute pancreatitis complicated by acute lung injury, and therefore provides a theoretical basis for the formulation of corresponding therapeutic measures in clinical practice for acute pancreatitis.

  13. Non-invasive ventilation used as an adjunct to airway clearance treatments improves lung function during an acute exacerbation of cystic fibrosis: a randomised trial

    Directory of Open Access Journals (Sweden)

    Tiffany J Dwyer

    2015-07-01

    Full Text Available Question: During an acute exacerbation of cystic fibrosis, is non-invasive ventilation beneficial as an adjunct to the airway clearance regimen? Design: Randomised controlled trial with concealed allocation and intention-to-treat analysis. Participants: Forty adults with moderate to severe cystic fibrosis lung disease and who were admitted to hospital for an acute exacerbation. Intervention: Comprehensive inpatient care (control group compared to the same care with the addition of non-invasive ventilation during airway clearance treatments from Day 2 of admission until discharge (experimental group. Outcome measures: Lung function and subjective symptom severity were measured daily. Fatigue was measured at admission and discharge on the Schwartz Fatigue Scale from 7 (no fatigue to 63 (worst fatigue points. Quality of life and exercise capacity were also measured at admission and discharge. Length of admission and time to next hospital admission were recorded. Results: Analysed as the primary outcome, the experimental group had a greater rate of improvement in forced expiratory volume in 1 second (FEV1 than the control group, but this was not statistically significant (MD 0.13% predicted per day, 95% CI –0.03 to 0.28. However, the experimental group had a significantly higher FEV1 at discharge than the control group (MD 4.2% predicted, 95% CI 0.1 to 8.3. The experimental group reported significantly lower levels of fatigue on the Schwartz fatigue scale at discharge than the control group (MD 6 points, 95% CI 1 to 11. There was no significant difference between the experimental and control groups in subjective symptom severity, quality of life, exercise capacity, length of hospital admission or time to next hospital admission. Conclusion: Among people hospitalised for an acute exacerbation of cystic fibrosis, the use of non-invasive ventilation as an adjunct to the airway clearance regimen significantly improves FEV1 and fatigue. Trial

  14. Acute exacerbations of fibrotic interstitial lung disease.

    Science.gov (United States)

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy.

  15. Lung function; Lungenfunktion

    Energy Technology Data Exchange (ETDEWEB)

    Sorichter, S. [Universitaetsklinikum Freiburg, Abteilung Pneumologie, Freiburg (Germany)

    2009-08-15

    The term lung function is often restricted to the assessment of volume time curves measured at the mouth. Spirometry includes the assessment of lung volumes which can be mobilised with the corresponding flow-volume curves. In addition, lung volumes that can not be mobilised, such as the residual volume, or only partially as FRC and TLC can be measured by body plethysmography combined with the determination of the airway resistance. Body plethysmography allows the correct positioning of forced breathing manoeuvres on the volume-axis, e.g. before and after pharmacotherapy. Adding the CO single breath transfer factor (T{sub LCO}), which includes the measurement of the ventilated lung volume using He, enables a clear diagnosis of different obstructive, restrictive or mixed ventilatory defects with and without trapped air. Tests of reversibility and provocation, as well as the assessment of inspiratory mouth pressures (PI{sub max}, P{sub 0.1}) help to classify the underlying disorder and to clarify treatment strategies. For further information and to complete the diagnostic of disturbances of the ventilation, diffusion and/or perfusion (capillar-)arterial bloodgases at rest and under physical strain sometimes amended by ergospirometry are recommended. Ideally, lung function measurements are amended by radiological and nuclear medicine techniques. (orig.) [German] Unter dem Begriff Lungenfunktion wird die Bestimmung der Lungenvolumina am Mund verstanden. Dabei werden die mobilisierbaren Lungenvolumina mit den zugehoerigen Fluss-Volumen-Kurven mittels Spirometrie und Ganzkoerperplethysmographie (GKP) und die nicht (RV) und teilweise mobilisierbaren Lungenvolumina (FRC, TLC) einschliesslich der Atemwegswiderstaende bestimmt. Die GKP ermoeglicht zusaetzlich die korrekte (Volumenachsen-)Positionierung der forcierten Atemmanoever. Dieses erlaubt eine uebersichtlichere graphische Darstellung z. B. vor und nach der Applikation pharmakologisch wirksamer Substanzen. Wird die GKP

  16. A lung function information system

    NARCIS (Netherlands)

    A.F.M. Verbraak (Anton); E.J. Hoorn (Ewout); J. de Vries (Julius); J.M. Bogaard (Jan); A. Versprille (Adrian)

    1991-01-01

    markdownabstractAbstract A lung function information system (LFIS) was developed for the data analysis of pulmonary function tests at different locations. This system was connected to the hospital information system (HIS) for the retrieval of patient data and the storage of the lung function varia

  17. TCM Therapeutic Strategy on Acute Lung Injury Caused by Infectious Atypical Pneumonia and Acute Respiratory Distress Syndrome

    Institute of Scientific and Technical Information of China (English)

    唐光华

    2003-01-01

    @@ Infectious atypical pneumonia (IAP) is also called severe acute respiratory syndrome (SARS) by WHO. In its development, around 20% of SARS can develop into the stage of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), active and effective treatment of it constitutes the important basis for lowering mortality and reducing secondary pulmonary function impairment and pulmonary fibrosis.

  18. Acute and subacute chemical-induced lung injuries: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Akira, Masanori, E-mail: Akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai City, Osaka 591-8555 (Japan); Suganuma, Narufumi [Department of Environmental Medicine, Kochi Medical School (Japan)

    2014-08-15

    Lung injury caused by chemicals includes bronchitis, bronchiolitis, chemical pneumonitis, pulmonary edema, acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and sarcoid-like granulomatous lung disease. Each chemical induces variable pathophysiology and the situation resembles to the drug induced lung disease. The HRCT features are variable and nonspecific, however HRCT may be useful in the evaluation of the lung injuries and so we should know about HRCT features of lung parenchymal abnormalities caused by chemicals.

  19. Surfactant for pediatric acute lung injury.

    Science.gov (United States)

    Willson, Douglas F; Chess, Patricia R; Notter, Robert H

    2008-06-01

    This article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is placed on reviewing clinical studies of surfactant therapy in pediatric and adult patients who have ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS.

  20. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  1. A review of pulmonary coagulopathy in acute lung injury, acute respiratory distress syndrome and pneumonia

    NARCIS (Netherlands)

    Nieuwenhuizen, Laurens; de Groot, Philip G.; Grutters, Jan C.; Biesma, Douwe H.

    2009-01-01

    Enhanced bronchoalveolar coagulation is a hallmark of many acute inflammatory lung diseases such as acute lung injury, acute respiratory distress syndrome and pneumonia. Intervention with natural anticoagulants in these diseases has therefore become a topic of interest. Recently, new data on the rol

  2. Transfusion-related acute lung injury:A case report

    Institute of Scientific and Technical Information of China (English)

    Emmanouil Petrou; Vasiliki Karali; Vasiliki Vartela

    2015-01-01

    Transfusion-related acute lung injury is the most common cause of serious morbidity and mortality associated with the transfusion of plasma-containing blood components. The syndrome can be confused with other causes of acute respiratory failure. Herein, we describe a 71-year-old man who was transfused with fresh frozen plasma due to prolonged INR, and died of what was considered as transfusion-related acute lung injury, despite treatment.

  3. Transfusion-related acute lung injury.

    Science.gov (United States)

    Federico, Anne

    2009-02-01

    Approximately one person in 5,000 will experience an episode of transfusion-related acute lung injury (TRALI) in conjunction with the transfusion of whole blood or blood components. Its hallmarks include hypoxemia, dyspnea, fever, hypotension, and bilateral pulmonary edema (noncardiogenic). The mortality for reported cases is 16.3%. The incidence and mortality may be even higher than estimated because of under-recognition and under-reporting. Although TRALI was identified as a clinical entity in the 1980s, a lack of consensus regarding a definition was present until 2004. An exact cause has yet to be identified; however, there are two theories regarding the etiology: the "antibody" and the "two-hit" theories. These theories involve both donor and recipient factors. Further education and research are needed to assist in the development of strategies for the prevention and treatment of TRALI.

  4. Acute lung injury induces cardiovascular dysfunction

    DEFF Research Database (Denmark)

    Suda, Koichi; Tsuruta, Masashi; Eom, Jihyoun;

    2011-01-01

    Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) down......-regulate the systemic expression of IL-6, but whether they can ameliorate the cardiovascular dysfunction related to ALI is uncertain. We sought to determine whether IL-6 contributes to the cardiovascular dysfunction related to ALI, and whether budesonide/formoterol ameliorates this process. Wild-type mice were...... these impairments (vasodilatory responses to acetylcholine, P = 0.005; cardiac output, P = 0.025). Pretreatment with the combination of budesonide and formoterol, but not either alone, ameliorated the vasodilatory responses to acetylcholine (P = 0.018) and cardiac output (P drugs also attenuated...

  5. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...... experienced a decline in lung function of more than 10% during the first 3 to 9 months after HSCT. The decline in forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity and diffusion capacity of the lung for carbon monoxide were strongly associated with acute graft...

  6. Therapeutic Strategies for Severe Acute Lung Injury

    Science.gov (United States)

    Diaz, Janet. V.; Brower, Roy; Calfee, Carolyn S.; Matthay, Michael A.

    2015-01-01

    Objective In the management of patients with severe Acute Lung Injury and the Acute Respiratory Distress Syndrome (ALI/ARDS), clinicians are sometimes challenged to maintain acceptable gas exchange while avoiding harmful mechanical ventilation practices. In some of these patients, physicians may consider the use of “rescue therapies” to sustain life. Our goal is to provide a practical, evidence-based review to assist critical care physicians’ care for patients with severe ALI/ARDS. Data Sources and Study Selection We searched the Pub Med database for clinical trials examining the use of the following therapies in ALI/ARDS: recruitment maneuvers, high positive end expiratory pressure, prone position, high frequency oscillatory ventilation, glucocorticoids, inhaled nitric oxide, buffer therapy and extracorporeal life support. Study selection All clinical trials that included patients with severe ALI/ARDS were included in the review. Data Synthesis The primary author reviewed the aforementioned trials in depth and then disputed findings and conclusions with other authors until consensus was achieved. Conclusions This article is designed to: a) provide clinicians with a simple, bedside definition for the diagnosis of severe ARDS; b) describe several therapies that can be used in severe ARDS with an emphasis on the potential risks as well as the indications and benefits; and c) to offer practical guidelines for implementation of these therapies. PMID:20562704

  7. Aerosolized prostacyclin for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)

    DEFF Research Database (Denmark)

    Afshari, Arash; Brok, Jesper; Møller, Ann

    2010-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions that are associated with high mortality and morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite the limited evidence available so far.......Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions that are associated with high mortality and morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite the limited evidence available so far....

  8. Lung injury in acute pancreatitis: mechanisms, prevention, and therapy.

    LENUS (Irish Health Repository)

    Shields, Conor J

    2012-02-03

    Lung injury is the most pertinent manifestation of extra-abdominal organ dysfunction in pancreatitis. The propensity of this retroperitoneal inflammatory condition to engender a diffuse and life-threatening lung injury is significant. Approximately one third of patients will develop acute lung injury and acute respiratory distress syndrome, which account for 60% of all deaths within the first week. The variability in the clinical course of pancreatitis renders it a vexing entity and makes demonstration of the efficacy of any specific intervention difficult. The distinct pathologic entity of pancreatitis-associated lung injury is reviewed with a focus on etiology and potential therapeutic maneuvers.

  9. Acute lung injury probably associated with infusion of propofol emulsion.

    Science.gov (United States)

    Chondrogiannis, K D; Siontis, G C M; Koulouras, V P; Lekka, M E; Nakos, G

    2007-08-01

    We present a case of acute lung injury associated with propofol infusion in a mechanically ventilated patient with intracerebral haemorrhage. Diagnosis was based on the exclusion of other risk factors inducing acute lung injury and on the clinical improvement after discontinuation of the propofol emulsion. Laboratory data such as the increase in total phospholipids, neutral lipids and free fatty acids in the broncho-alveolar lavage fluid, the remarkably high percentage of alveolar macrophages including fat droplets and the similar lipid composition of propofol and broncho-alveolar lavage fluid support the relationship between propofol and acute lung injury.

  10. [Positive end-expiratory pressure : adjustment in acute lung injury].

    Science.gov (United States)

    Bruells, C S; Dembinski, R

    2012-04-01

    Treatment of patients suffering from acute lung injury is a challenge for the treating physician. In recent years ventilation of patients with acute hypoxic lung injury has changed fundamentally. Besides the use of low tidal volumes, the most beneficial setting of positive end-expiratory pressure (PEEP) has been in the focus of researchers. The findings allow adaption of treatment to milder forms of acute lung injury and severe forms. Additionally computed tomography techniques to assess the pulmonary situation and recruitment potential as well as bed-side techniques to adjust PEEP on the ward have been modified and improved. This review gives an outline of recent developments in PEEP adjustment for patients suffering from acute hypoxic and hypercapnic lung injury and explains the fundamental pathophysiology necessary as a basis for correct treatment.

  11. Transfusion related acute lung injury presenting with acute dyspnoea: a case report

    Directory of Open Access Journals (Sweden)

    Haji Altaf

    2008-10-01

    Full Text Available Abstract Introduction Transfusion-related acute lung injury is emerging as a common cause of transfusion-related adverse events. However, awareness about this entity in the medical fraternity is low and it, consequently, remains a very under-reported and often an under-diagnosed complication of transfusion therapy. Case presentation We report a case of a 46-year old woman who developed acute respiratory and hemodynamic instability following a single unit blood transfusion in the postoperative period. Investigation results were non-specific and a diagnosis of transfusion-related acute lung injury was made after excluding other possible causes of acute lung injury. She responded to symptomatic management with ventilatory and vasopressor support and recovered completely over the next 72 hours. Conclusion The diagnosis of transfusion-related acute lung injury relies on excluding other causes of acute pulmonary edema following transfusion, such as sepsis, volume overload, and cardiogenic pulmonary edema. All plasma containing blood products have been implicated in transfusion-related acute lung injury, with the majority being linked to whole blood, packed red blood cells, platelets, and fresh-frozen plasma. The pathogenesis of transfusion-related acute lung injury may be explained by a "two-hit" hypothesis, involving priming of the inflammatory machinery and then activation of this primed mechanism. Treatment is supportive, with prognosis being substantially better than for most other causes of acute lung injury.

  12. Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

    Directory of Open Access Journals (Sweden)

    Cuzzocrea Salvatore

    2007-10-01

    Full Text Available Abstract In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1 TNF-α production in pleural exudates and in the lung tissues, (2 the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity, (3 the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry and (4 apoptosis (TUNEL staining, Bax, Bcl-2 expression. Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction.

  13. B-lines quantify the lung water content: a lung ultrasound versus lung gravimetry study in acute lung injury.

    Science.gov (United States)

    Jambrik, Zoltán; Gargani, Luna; Adamicza, Agnes; Kaszaki, József; Varga, Albert; Forster, Tamás; Boros, Mihály; Picano, Eugenio

    2010-12-01

    B-lines (also termed ultrasound lung comets) obtained with lung ultrasound detect experimental acute lung injury (ALI) very early and before hemogasanalytic changes, with a simple, noninvasive, nonionizing and real-time method. Our aim was to estimate the correlation between B-lines number and the wet/dry ratio of the lung tissue, measured by gravimetry, in an experimental model of ALI. Seventeen Na-pentobarbital anesthetized, cannulated (central vein and carotid artery) minipigs were studied: five sham-operated animals served as controls and, in 12 animals, ALI was induced by injection of oleic acid (0.1 mL/kg) via the central venous catheter. B-lines were measured by echographic scanner in four predetermined chest scanning sites in each animal. At the end of each experiment, both lungs were dissected, weighed and dried to determine wet/dry weight ratio by gravimetry. After the injection of oleic acid, B-lines number increased over time. A significant correlation was found between the wet/dry ratio and B-lines number (r = 0.91, p < 0.001). These data suggest that in an experimental pig model of ALI/ARDS, B-lines assessed by lung ultrasound provide a simple, semiquantitative, noninvasive index of lung water accumulation, strongly correlated to invasive gravimetric assessment.

  14. DISTINCT PHENOTYPES OF INFILTRATING CELLS DURING ACUTE AND CHRONIC LUNG REJECTION IN HUMAN HEART-LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; CLELLAND, C; GOUW, ASH; PROP, J

    1995-01-01

    To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung rejection

  15. High mobility group box 1 protein as a late-acting mediator of acute lung inflammation.

    Science.gov (United States)

    Lutz, Waldemar; Stetkiewicz, Jan

    2004-01-01

    Acute inflammatory lung injury is often a delayed complication of critical illness and is associated with increased mortality. High mobility group box 1 (HMGB1) protein, in addition to its role as a transcriptional regulator factor, has been identified as a late mediator of endotoxin lethality and might be also involved in the development and progression of acute lung injury. HMGB1 protein itself can cause an acute inflammatory response manifested by increased production of proinflammatory cytokines and neutrophil accumulation. The delayed kinetics of HMGB1 protein release indicate that this protein is a distal mediator of acute inflamatory lung injury. Anti-HMGB1 protein antibodies attenuated endotoxin-induced lung injury, but not the early release of TNF-alpha and IL-1beta, indicating that HMGB1 protein is a late mediator of endotoxin-induced acute lung injury. HMGB1 protein is not released by apoptotic cells but is passively released by necrotic or damaged somatic and immune cells and it functions as a major stimulus of necrosis-induced inflammation. HMGB1 protein is also released by activated monocytes/macrophages and induces delayed and biphasic release of proinflammatory mediators from these cells. HMGB1 protein failed to stimulate cytokines release in lymphocytes, indicating that cellular stimulation is specific. We would like to suggest that HMGB1 protein may be also a primary mediator of the inflammatory responses to lung cells injury caused by toxic environmental chemicals.

  16. Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

    Directory of Open Access Journals (Sweden)

    Chih-Cheng Lai

    2014-08-01

    Full Text Available Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI in patients with acute respiratory distress syndrome (ARDS. Here, we examined potential benefits of glutamine (GLN on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer’s solution (vehicle control thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV of 15 mL/kg and zero positive end-expiratory pressure (PEEP or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology, neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory.

  17. What Are Lung Function Tests?

    Science.gov (United States)

    ... include tests that measure lung size and air flow, such as spirometry and lung volume tests. Other tests measure how well gases such as oxygen get in and out of your blood. These tests include pulse oximetry and arterial blood ...

  18. Acute lung injury and the acute respiratory distress syndrome in the injured patient

    Directory of Open Access Journals (Sweden)

    Bakowitz Magdalena

    2012-08-01

    Full Text Available Abstract Acute lung injury and acute respiratory distress syndrome are clinical entities of multi-factorial origin frequently seen in traumatically injured patients requiring intensive care. We performed an unsystematic search using PubMed and the Cochrane Database of Systematic Reviews up to January 2012. The purpose of this article is to review recent evidence for the pathophysiology and the management of acute lung injury/acute respiratory distress syndrome in the critically injured patient. Lung protective ventilation remains the most beneficial therapy. Future trials should compare intervention groups to controls receiving lung protective ventilation, and focus on relevant outcome measures such as duration of mechanical ventilation, length of intensive care unit stay, and mortality.

  19. Acute Lung Injury during Antithymocyte Globulin Therapy for Aplastic Anemia

    Directory of Open Access Journals (Sweden)

    Ewan Christopher Goligher

    2009-01-01

    Full Text Available The case of a 33-year-old man with aplastic anemia who experienced recurrent episodes of hypoxemia and pulmonary infiltrates during infusions of antithymocyte globulin (ATG is described. With the use of high-dose corticosteroids, the patient’s original episodes resolved, and were subsequently prevented before additional administrations of ATG. Rare reports of an association between ATG and acute lung injury are found in the literature, but this is the first report of successful steroid-supported re-exposure. Although the mechanism of ATG-related acute lung injury remains uncertain, it may be parallel to the mechanism of transfusion-related acute lung injury because the pathogenesis of the latter relies, in part, on antileukocyte antibodies. ATG-related toxicity should be included in the differential diagnosis of new, infusion-associated pulmonary infiltrates, and corticosteroids may be a useful therapeutic consideration in the management.

  20. Transfusion-related acute lung injury: report of two cases.

    Science.gov (United States)

    Čermáková, Z; Kořískta, M; Blahutová, Š; Dvořáčková, J; Brát, R; Valkovský, I; Hrdličková, R

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a severe life-threatening complication of blood transfusion, characterized by acute lung injury developing within 2-6 h of transfusion. However, TRALI is difficult to diagnose, and the initial report or suspicion of TRALI depends on close collaboration between clinical departments and transfusion centres. A total of 17 adverse post-transfusion reactions were reported to the Blood Centre of the University Hospital Ostrava as suspected TRALI between 2005 and 2010. We report two cases of serious TRALI with different pathogenetic mechanisms.

  1. Neutrophils contain cholesterol crystals in transfusion-related acute lung injury (TRALI)

    DEFF Research Database (Denmark)

    Van Ness, Michael; Jensen, Hanne; Adamson, Grete N

    2013-01-01

    Intracellular components of transfusion-related acute lung injury (TRALI) were investigated by transmission electron microscopy.......Intracellular components of transfusion-related acute lung injury (TRALI) were investigated by transmission electron microscopy....

  2. Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury.

    Science.gov (United States)

    Nardelli, L M; Rzezinski, A; Silva, J D; Maron-Gutierrez, T; Ornellas, D S; Henriques, I; Capelozzi, V L; Teodoro, W; Morales, M M; Silva, P L; Pelosi, P; Garcia, C S N B; Rocco, P R M

    2015-01-01

    We investigated the effects of acute hypercapnic acidosis and buffered hypercapnia on lung inflammation and apoptosis in experimental acute lung injury (ALI). Twenty-four hours after paraquat injection, 28 Wistar rats were randomized into four groups (n=7/group): (1) normocapnia (NC, PaCO2=35-45 mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70 mmHg), ventilated with 5%CO2+21%O2+balancedN2; and (3) buffered hypercapnic acidosis (BHC), ventilated with 5%CO2+21%O2+balancedN2 and treated with sodium bicarbonate (8.4%). The remaining seven animals were not mechanically ventilated (NV). The mRNA expression of interleukin (IL)-6 (p=0.003), IL-1β (pacidosis, reduced lung inflammation and lung and kidney cell apoptosis.

  3. Patient-ventilator interaction during acute lung injury, and the role of spontaneous breathing: part 1: respiratory muscle function during critical illness.

    Science.gov (United States)

    Kallet, Richard H

    2011-02-01

    Since the early 1970s there has been an ongoing debate regarding the wisdom of promoting unassisted spontaneous breathing throughout the course of critical illness in patients with severe respiratory failure. The basis of this debate has focused on the clinical relevance of opposite problems. Historically, the term "disuse atrophy" has described a situation wherein sustained inactivity of the respiratory muscles (ie, passive ventilation) results in deconditioning and weakness. More recently it has been referred to as "ventilator-induced diaphragmatic dysfunction." In contrast, "use atrophy" describes a situation where chronic high-tension inspiratory work causes structural damage to the diaphragm and weakness. Both laboratory and clinical studies demonstrated that relatively brief periods of complete respiratory muscle inactivity, as well as intense muscle loading, result in acute inflammation, loss of muscle mass, and weakness. Yet in critical illness other factors also affect respiratory muscle function, including prolonged use of neuromuscular blocking agents, administration of corticosteroids, and sepsis. This makes the attribution of acquired respiratory muscle weakness and ventilator-dependence to either ventilator-induced diaphragmatic dysfunction or loaded breathing extremely difficult. Regardless, the clinical implications of this research strongly suggest that passive mechanical ventilation should be avoided whenever possible. However, promotion of unassisted spontaneous breathing in the acute phase of critical illness also may carry a substantial risk of respiratory muscle injury and weakness. Use of mechanical ventilation modes in a manner that induces spontaneous breathing effort, while simultaneously reducing the work load on the respiratory muscles, is probably sufficient to minimize both problems.

  4. Activated protein C in the treatment of acute lung injury and acute respiratory distress syndrome

    NARCIS (Netherlands)

    A.D. Cornet; G.P. van Nieuw Amerongen; A. Beishuizen; M.J. Schultz; A.R.J. Girbes; A.B.J. Groeneveld

    2009-01-01

    Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) frequently necessitate mechanical ventilation in the intensive care unit. The syndromes have a high mortality rate and there is at present no treatment specifically directed at the underlying pathogenesis. Central in

  5. Epidemiology of acute lung injury and acute respiratory distress syndrome in The Netherlands : A survey

    NARCIS (Netherlands)

    Wind, Jan; Versteegt, Jens; Twisk, Jos; van der Werf, Tjip S.; Bindels, Alexander J. G. H.; Spijkstra, Jan-Jaap; Girbes, Armand R. J.; Groeneveld, A. B. Johan

    2007-01-01

    Background: The characteristics, incidence and risk factors for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) may depend on definitions and geography. Methods: A prospective, 3-day point-prevalence study was performed by a survey of all intensive care units (ICU) in the Neth

  6. Acute fibrinous and organising pneumonia: a rare histopathological variant of chemotherapy-induced lung injury.

    Science.gov (United States)

    Gupta, Arjun; Sen, Shiraj; Naina, Harris

    2016-04-06

    Bleomycin-induced lung injury is the most common chemotherapy-associated lung disease, and is linked with several histopathological patterns. Acute fibrinous and organising pneumonia (AFOP) is a relatively new and rare histological pattern of diffuse lung injury. We report the first known case of bleomycin-induced AFOP. A 36-year-old man with metastatic testicular cancer received three cycles of bleomycin, etoposide and cisplatin, before being transitioned to paclitaxel, ifosfamide and cisplatin. He subsequently presented with exertional dyspnoea, cough and pleuritic chest pain. CT of the chest demonstrated bilateral ground glass opacities with peribronchovascular distribution and pulmonary function tests demonstrated a restrictive pattern of lung disease with impaired diffusion. Transbronchial biopsy revealed intra-alveolar fibrin deposits with organising pneumonia, consisting of intraluminal loose connective tissue consistent with AFOP. The patient received high-dose corticosteroids with symptomatic and radiographic improvement. AFOP should be recognised as a histopathological variant of bleomycin-induced lung injury.

  7. Lung function tests in neonates and infants with chronic lung disease: lung and chest-wall mechanics.

    Science.gov (United States)

    Gappa, Monika; Pillow, J Jane; Allen, Julian; Mayer, Oscar; Stocks, Janet

    2006-04-01

    This is the fifth paper in a review series that summarizes available data and critically discusses the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). This review focuses on respiratory mechanics, including chest-wall and tissue mechanics, obtained in the intensive care setting and in infants during unassisted breathing. Following orientation of the reader to the subject area, we focused comments on areas of enquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically with respect to relevant methods, equipment and study design, limitations and strengths of different techniques, and availability and appropriateness of reference data. Recommendations to guide future investigations in this field are provided. Numerous different methods have been used to assess respiratory mechanics with the aims of describing pulmonary status in preterm infants and assessing the effect of therapeutic interventions such as surfactant treatment, antenatal or postnatal steroids, or bronchodilator treatment. Interpretation of many of these studies is limited because lung volume was not measured simultaneously. In addition, populations are not comparable, and the number of infants studied has generally been small. Nevertheless, results appear to support the pathophysiological concept that immaturity of the lung leads to impaired lung function, which may improve with growth and development, irrespective of the diagnosis of chronic lung disease. To fully understand the impact of immaturity on the developing lung, it is unlikely that a single parameter such as respiratory compliance or resistance will accurately describe underlying changes. Assessment of respiratory mechanics will have to be supplemented by assessment of lung volume and airway function. New methods such as the low-frequency forced oscillation technique, which

  8. Supplementation of parenteral nutrition with fish oil attenuates acute lung injury in a rat model

    Science.gov (United States)

    Kohama, Keisuke; Nakao, Atsunori; Terashima, Mariko; Aoyama-Ishikawa, Michiko; Shimizu, Takayuki; Harada, Daisuke; Nakayama, Mitsuo; Yamashita, Hayato; Fujiwara, Mayu; Kotani, Joji

    2014-01-01

    Fish oil rich in n-3 polyunsaturated fatty acids has diverse immunomodulatory properties and attenuates acute lung injury when administered in enternal nutrition. However, enteral nutrition is not always feasible. Therefore, we investigated the ability of parenteral nutrition supplemented with fish oil to ameliorate acute lung injury. Rats were infused with parenteral nutrition solutions (without lipids, with soybean oil, or with soybean oil and fish oil) for three days. Lipopolysaccharide (15 mg/kg) was then administered intratracheally to induce acute lung injury, characterized by impaired lung function, polymorphonuclear leukocyte recruitment, parenchymal tissue damage, and upregulation of mRNAs for inflammatory mediators. Administration of parenteral nutrition supplemented with fish oil prior to lung insult improved gas exchange and inhibited neutrophil recruitment and upregulation of mRNAs for inflammatory mediators. Parenteral nutrition supplemented with fish oil also prolonged survival. To investigate the underlying mechanisms, leukotriene B4 and leukotriene B5 secretion was measured in neutrophils from the peritoneal cavity. The neutrophils from rats treated with fish oil-rich parenteral nutrition released significantly more leukotriene B5, an anti-inflammatory eicosanoid, than neutrophils isolated from rats given standard parenteral nutrition. Parenteral nutrition with fish oil significantly reduced lipopolysaccharide-induced lung injury in rats in part by promoting the synthesis of anti-inflammatory eicosanoids. PMID:24688221

  9. Acute lung injury and ARDS in acute pancreatitis: Mechanisms and potential intervention

    Institute of Scientific and Technical Information of China (English)

    Roland; Andersson

    2010-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in acute pancreatitis still represents a substantial problem,with a mortality rate in the range of 30%-40%.The present review evaluates underlying pathophysiological mechanisms in both ALI and ARDS and potential clinical implications.Several mediators and pathophysiological pathways are involved during the different phases of ALI and ARDS.The initial exudative phase is characterized by diffuse alveolar damage,microvascular injury and inf...

  10. Strategies to improve oxygenation in experimental acute lung injury

    NARCIS (Netherlands)

    A. Hartog (Arthur)

    2000-01-01

    textabstractOne of the most important clinical syndromes, in which failure of oxygen uptake in the lung leads to severe hypoxia, is the so-called acute respiratory distress syndrome (ARDS). ARDS is a complex of clinical signs and symptoms which occur following diverse pulmonary or systemic insults,

  11. Life-threatening acute lung injury after gamma butyrolactone ingestion

    NARCIS (Netherlands)

    van Gerwen, M.; Scheper, H.; Touw, D. J.; van Nieuwkoop, C.

    2015-01-01

    We describe a case of a 44-year-old woman with a borderline personality disorder and chronic gamma-butyrolactone (GBL) use who presented with progressive dyspnoea and an altered mental status. A high anion gap metabolic acidosis and acute lung injury was diagnosed. We hypothesise this was caused by

  12. Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults.

    Science.gov (United States)

    Gold, Diane R; Litonjua, Augusto A; Carey, Vincent J; Manson, JoAnn E; Buring, Julie E; Lee, I-Min; Gordon, David; Walter, Joseph; Friedenberg, Georgina; Hankinson, John L; Copeland, Trisha; Luttmann-Gibson, Heike

    2016-03-01

    Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial-the VITamin D and OmegA-3 TriaL (VITAL)--to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review.

  13. The Role of Neutrophil Collagenase in Endotoxic Acute Lung Injury

    Institute of Scientific and Technical Information of China (English)

    徐涛; 曾邦雄; 李兴旺

    2004-01-01

    The aim of this study was to determine the role of neutrophil collagenase in the pathogenesis of acute lung injury induced by endotoxin. 28 Sprague-Dawley were randomized into control group and LPS-enduced groups. Samples of left lung were obtained in 2 h (group L1 ), 6 h (group L2), 12 h (group L3 ) after intravenous LPS. Immunohistochemsitry was employed for detection of expression of neutrophil collagenase. Pathological scores, lung wet/dry weight ratio and the number of neutrophils were measured. The results showed that the concentration of neutrophil collagenase in LPS-enduced groups (group L1, L2, L3 ) were significantly higher than that of control group (P<0.01). Pathological scores, lung wet/dry weight ratio and the number of neutrophils in LPS-enduced groups (group L1, L2, L3 ) were also significantly higher than that of control group (P<0.01).Moreover, among group L1, L2 and L3, there were significant correlations in concentration of neutrophil collagenase and pathological scores, lung wet/dry weight ratio, the number of neutrophils (P<0.05). The present study showed that neutrophil collagenase play an important role in the pathogenesis and progress of endotoxic acute lung injury.

  14. Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats.

    Science.gov (United States)

    Wang, Wen; Liu, Zhi; Su, Jie; Chen, Wen-Sheng; Wang, Xiao-Wu; Bai, San-Xing; Zhang, Jin-Zhou; Yu, Shi-Qiang

    2016-08-01

    Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of-function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3'-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR-155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI.

  15. Crocin attenuates lipopolysacchride-induced acute lung injury in mice

    Science.gov (United States)

    Wang, Jian; Kuai, Jianke; Luo, Zhonghua; Wang, Wuping; Wang, Lei; Ke, Changkang; Li, Xiaofei; Ni, Yunfeng

    2015-01-01

    Crocin, a representative of carotenoid compounds, exerts a spectrum of activities including radical scavenger, anti-microbial and anti-inflammatory properties. To investigate the protective effect of crocin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg). The mice received intragastric injection of crocin (50 mg/kg) 1 h before LPS administration. Pulmonary histological changes were evaluated by hematoxylineosin stain and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nitric oxide (NO), and myeloperoxidase (MPO) activity were measured by enzymelinked immunosorbent assay. Expression of inducible nitric oxide synthase (iNOS) in lung tissues was determined by Western blot analysis. Crocin pretreatment significantly alleviated the severity of lung injury and inhibited the production of TNF-α and IL-1β in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by crocin pretreatment. Crocin pretreatment also reduced the concentrations of NO in lung tissues. Furthermore, the expression of iNOS was significantly suppressed by crocin pretreatment. Croncin potently protected against LPS-induced ALI and the protective effects of crocin may attribute partly to the suppression of iNOS expression. PMID:26191176

  16. Lung function in Pakistani wood workers.

    Science.gov (United States)

    Meo, Sultan A

    2006-06-01

    The lung function impairment is the most common respiratory problem in industrial plants and their vicinity. Therefore, the purpose was to study the affects of wood dust and its duration of exposure on lung function. This was a matched cross-sectional study of Spirometry in 46 non-smoking wood workers with age range 20 - 60 years, who worked without the benefit of wood dust control ventilation or respiratory protective devices. Pulmonary function test was performed by using an electronic Spirometer. Significant reduction was observed in the mean values of Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), and Maximum Voluntary Ventilation (MVV) in wood workers relative to their matched controls. This impairment was increased with the duration of exposure to wood industries. It is concluded that lung function in wood workers is impaired and stratification of results shows a dose-response effect of years of wood dust exposure on lung function.

  17. Independent lung ventilation in a newborn with asymmetric acute lung injury due to respiratory syncytial virus: a case report

    Directory of Open Access Journals (Sweden)

    Di Nardo Matteo

    2008-06-01

    Full Text Available Abstract Introduction Independent lung ventilation is a form of protective ventilation strategy used in adult asymmetric acute lung injury, where the application of conventional mechanical ventilation can produce ventilator-induced lung injury and ventilation-perfusion mismatch. Only a few experiences have been published on the use of independent lung ventilation in newborn patients. Case presentation We present a case of independent lung ventilation in a 16-day-old infant of 3.5 kg body weight who had an asymmetric lung injury due to respiratory syncytial virus bronchiolitis. We used independent lung ventilation applying conventional protective pressure controlled ventilation to the less-compromised lung, with a respiratory frequency proportional to the age of the patient, and a pressure controlled high-frequency ventilation to the atelectatic lung. This was done because a single tube conventional ventilation protective strategy would have exposed the less-compromised lung to a high mean airways pressure. The target of independent lung ventilation is to provide adequate gas exchange at a safe mean airways pressure level and to expand the atelectatic lung. Independent lung ventilation was accomplished for 24 hours. Daily chest radiograph and gas exchange were used to evaluate the efficacy of independent lung ventilation. Extubation was performed after 48 hours of conventional single-tube mechanical ventilation following independent lung ventilation. Conclusion This case report demonstrates the feasibility of independent lung ventilation with two separate tubes in neonates as a treatment of an asymmetric acute lung injury.

  18. Acute fibrinous and organising pneumonia following lung transplantation is associated with severe allograft dysfunction and poor outcome: a case series

    Directory of Open Access Journals (Sweden)

    Keith Meyer

    2015-01-01

    Full Text Available   Acute fibrinous and organising pneumonia (AFOP is a histopathologic variant of acute lung injury that has been associated with infection and inflammatory disorders and has been reported as a complication of lung transplantation. A retrospective chart review was performed for all patients transplanted at the University of Wisconsin Hospital and Clinics from January 1995 to December 2013 (n = 561. We identified 6 recipients whose clinical course was complicated by AFOP. All recipients were found to have AFOP on lung biopsy or at post-mortem examination, and 5 of the 6 patients suffered progressive allograft dysfunction that led to fatal outcome. Only 1 of the 6 patients stabilised with augmented immunosuppression and had subsequent improvement and stabilisation of allograft function. We could not clearly identify any specific cause of AFOP, such as drug toxicity or infection. Lung transplantation can be complicated by lung injury with an AFOP pattern on histopathologic examination of lung biopsy specimens. The presence of an AFOP pattern was associated with irreversible decline in lung function that was refractory to therapeutic interventions in 5 of our 6 cases and was associated with severe allograft dysfunction and death in these 5 individuals. AFOP should be considered as a potential diagnosis when lung transplant recipients develop progressive decline in lung function that is consistent with a clinical diagnosis of chronic lung allograft dysfunction.  

  19. Cold stress aggravates inflammatory responses in an LPS-induced mouse model of acute lung injury

    Science.gov (United States)

    Joo, Su-Yeon; Park, Mi-Ju; Kim, Kyun-Ha; Choi, Hee-Jung; Chung, Tae-Wook; Kim, Yong Jin; Kim, Joung Hee; Kim, Keuk-Jun; Joo, Myungsoo; Ha, Ki-Tae

    2016-08-01

    Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation.

  20. Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Acute Lung Injury and Other Inflammatory Lung Diseases

    Science.gov (United States)

    Monsel, Antoine; Zhu, Ying-gang; Gudapati, Varun; Lim, Hyungsun; Lee, Jae W.

    2017-01-01

    Introduction Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. Areas covered The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. Expert opinion While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification. PMID:27011289

  1. Prone positioning ventilation for treatment of acute lung injury and acute respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    LAN Mei-juan; HE Xiao-di

    2009-01-01

    Patients who are diagnosed with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) usually have ventilation-perfusion mismatch, severe decrease in lung capacity, and gas exchange abnormalities. Health care work-ers have implemented various strategies in an attempt to compensate for these pathological alterations. By rotating patients with ALI/ARDS between the supine and prone position, it is possible to achieve a significant improvement in PaO2/FiO2, decrease shunting and therefore improve oxy-genation without use of expensive, invasive and experimen-tal procedures.

  2. Paediatric lung function testing : determinants and reference values

    NARCIS (Netherlands)

    Koopman, Marije

    2011-01-01

    Paediatric lung function tests provide objective measures in diagnosis and follow-up of lung diseases, and give insight in the pathophysiology of lung growth and development. In the first part of the thesis, paediatric lung function tests were used to investigate determinants of lung growth and deve

  3. Galangin dampens mice lipopolysaccharide-induced acute lung injury.

    Science.gov (United States)

    Shu, Yu-Sheng; Tao, Wei; Miao, Qian-Bing; Lu, Shi-Chun; Zhu, Ya-Bing

    2014-10-01

    Galangin, an active ingredient of Alpinia galangal, has been shown to possess anti-inflammatory and antioxidant activities. Inflammation and oxidative stress are known to play vital effect in the pathogenesis of acute lung injury (ALI). In this study, we determined whether galangin exerts lung protection in lipopolysaccharide (LPS)-induced ALI. Male BALB/c mice were randomized to receive galangin or vehicle intraperitoneal injection 3 h after LPS challenge. Samples were harvested 24 h post LPS administration. Galangin administration decreased biochemical parameters of oxidative stress and inflammation, and improved oxygenation and lung edema in a dose-dependent manner. These protective effects of galangin were associated with inhibition of nuclear factor (NF)-κB and upregulation of heme oxygenase (HO)-1. Galangin reduces LPS-induced ALI by inhibition of inflammation and oxidative stress.

  4. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    Directory of Open Access Journals (Sweden)

    Xiaomei Feng

    Full Text Available Rats with Metabolic Syndrome (MetaS have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S. aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS and high capacity runner (HCR rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF, and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  5. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    Science.gov (United States)

    Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G; Britton, Steven L; Hellman, Judith

    2015-01-01

    Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  6. Role of macrophage chemoattractant protein-1 in acute inflammation after lung contusion.

    Science.gov (United States)

    Suresh, Madathilparambil V; Yu, Bi; Machado-Aranda, David; Bender, Matthew D; Ochoa-Frongia, Laura; Helinski, Jadwiga D; Davidson, Bruce A; Knight, Paul R; Hogaboam, Cory M; Moore, Bethany B; Raghavendran, Krishnan

    2012-06-01

    Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2(-/-)) mice. Rats injected with a polyclonal antibody to CCL-2 showed higher levels of albumin and IL-6 in the bronchoalveolar lavage and myeloperoxidase in the lung tissue after LC. Closed-chest bilateral LC demonstrated CCL-2 localization in alveolar macrophages (AMs) and epithelial cells. Subsequent experiments performed using a murine model of LC showed that the extent of injury, assessed by pulmonary compliance and albumin levels in the bronchoalveolar lavage, was higher in the CCR2(-/-) mice when compared with the wild-type (WT) mice. We also found increased release of IL-1β, IL-6, macrophage inflammatory protein-1, and keratinocyte chemoattractant, lower recruitment of AMs, and higher neutrophil infiltration and phagocytic activity in CCR2(-/-) mice at 24 hours. However, impaired phagocytic activity was observed at 48 hours compared with the WT. Production of CCL-2 and macrophage chemoattractant protein-5 was increased in the absence of CCR2, thus suggesting a negative feedback mechanism of regulation. Isolated AMs in the CCR2(-/-) mice showed a predominant M1 phenotype compared with the predominant M2 phenotype in WT mice. Taken together, the above results show that CCL-2 is functionally important in the down-modulation of injury and inflammation in LC.

  7. Using bosentan to treat paraquat poisoning-induced acute lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Zhongchen Zhang

    Full Text Available BACKGROUND: Paraquat poisoning is well known for causing multiple organ function failure (MODS and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning. OBJECTIVE: To study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat. METHOD: A total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning; the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day; and a control group (rats were administered intragastric physiological saline. On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1, endothelin-1 (ET-1, and hydroxyproline (HYP in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes. RESULT: The TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered. CONCLUSION: Bosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.

  8. The clinical significance of lung hypoexpansion in acute childhood asthma

    Energy Technology Data Exchange (ETDEWEB)

    Spottswood, Stephanie E. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University Health System, Box 980615, 23298-0615, Richmond, VA (United States); Department of Radiology, The Children' s Hospital of the King' s Daughters, 601 Children' s Lane, Norfolk, VA 23507 (United States); Allison, Kelley Z.; Narla, Lakshmana D.; Lowry, Patricia A. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University Health System, Box 980615, 23298-0615, Richmond, VA (United States); Lopatina, Olga A.; Sethi, Narinder N. [School of Medicine, Medical College of Virginia, Virginia Commonwealth University Health System, Richmond, VA (United States); Nettleman, Mary D. [Department of Internal Medicine, B-427 Clinical Center, Michigan State University, East Lansing, MI 48824 (United States)

    2004-04-01

    Many children experiencing acute asthmatic episodes have chest radiographs, which may show lung hyperinflation, hypoinflation, or normal inflation. Lung hypoinflation may be a sign of respiratory fatigue and poor prognosis. To compare the clinical course in children with asthma according to the degree of lung inflation on chest radiographs. We conducted a retrospective study during a 24-month period (from July 1999 to July 2001) of children aged 0-17 years, who presented to a pediatric emergency department or outpatient clinic with an asthma exacerbation. Chest radiographs obtained at presentation were reviewed independently by three pediatric radiologists who were blinded to the admission status of the patient. The correlation between hypoinflation and hospital admission was assessed in three age groups: 0-2 years, 3-5 years, and 6-17 years. Hypoinflation on chest radiographs was significantly correlated with hospital admission for children aged 6-17 years (odds ratio 16.00, 95% confidence interval 1.89-135.43). The inter-reader agreement for interpretation of these radiographs was strong, with a kappa score of 0.76. Hypoinflation was not correlated with admission in younger children. Lung hypoinflation is associated with a greater likelihood of hospital admission in children aged 6 years or older. Therefore, hypoinflation was a poor prognostic sign and may warrant more aggressive therapy. (orig.)

  9. Desferrioxamine attenuates minor lung injury following surgical acute liver failure.

    Science.gov (United States)

    Kostopanagiotou, G G; Kalimeris, K A; Arkadopoulos, N P; Pafiti, A; Panagopoulos, D; Smyrniotis, V; Vlahakos, D; Routsi, C; Lekka, M E; Nakos, G

    2009-06-01

    Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF. 14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg x kg(-1) x h(-1) for the first 6 h post-operatively and 2.4 mg x kg(-1) x h(-1) until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A(2) activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA(2), platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals. DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA(2) and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and prevents alveolar space collapse.

  10. Exhaled CO, a predictor of lung function?

    DEFF Research Database (Denmark)

    Fabricius, Peder; Scharling, Henrik; Løkke, Anders;

    2007-01-01

    ; in total 3738 subjects, 2096 women and 1642 men. RESULTS: Subjects not inhaling had slightly lower exhaled CO values than those inhaling, but substantially higher values than non-smokers (P....001). Increasing CO levels were correlated to a lower FEV(1)%pred and to an accelerated decline in lung function. However, in multiple linear regression analyses these correlations were not significant. CONCLUSION: Inhalation and type of cigarette affects exhaled CO levels. CO measures have no predictive value......BACKGROUND: Smoking is associated with an accelerated loss of lung function and inhalation accelerates the decline further. Exhaled CO reflects the exposure of smoke to the lungs. AIM: To investigate whether self-reported inhalation and type of cigarette influenced the level of exhaled CO...

  11. Pulmonary Surfactants for Acute and Chronic Lung Diseases (Part II

    Directory of Open Access Journals (Sweden)

    O. A. Rozenberg

    2014-01-01

    Full Text Available Part 2 of the review considers the problem of surfactant therapy for acute respiratory distress syndrome (ARDS in adults and young and old children. It gives information on the results of surfactant therapy and prevention of ARDS in patients with severe concurrent trauma, inhalation injuries, complications due to complex expanded chest surgery, or severe pneumonias, including bilateral pneumonia in the presence of A/H1N1 influenza. There are data on the use of a surfactant in obstetric care and prevention of primary graft dysfunction during lung transplantation. The results of longterm use of surfactant therapy in Russia, suggesting that death rates from ARDS may be substantially reduced (to 20% are discussed. Examples of surfactant therapy for other noncritical lung diseases, such as permanent athelectasis, chronic obstructive pulmonary diseases, and asthma, as well tuberculosis, are also considered.

  12. XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury

    Science.gov (United States)

    Toba, Hiroaki; Tomankova, Tereza; Wang, Yingchun; Bai, Xiaohui; Cho, Hae-Ra; Guan, Zhehong; Adeyi, Oyedele A.; Tian, Feng; Keshavjee, Shaf; Liu, Mingyao

    2016-01-01

    XB130 is a novel oncoprotein that promotes cancer cell survival, proliferation and migration. Its physiological function in vivo is largely unknown. The objective of this study was to determine the role of XB130 in lipopolysaccharide (LPS)-induced septic responses and acute lung injury. LPS was intraperitoneally administrated to Xb130 knockout (KO) and wild type (WT) mice. There was a significant weight loss in KO mice at Day 2 and significantly higher disease scores during the 7 days of observation. The levels of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in the serum were significantly higher in KO mice at Day 2. In KO mice there were a significantly higher lung injury score, higher wet/dry lung weight ratio, more apoptotic cells and less proliferative cells in the lung. Macrophage infiltration was significantly elevated in the lung of KO mice. There was significantly increased number of p-GSK-3β positive cells in KO mice, which were mainly neutrophils and macrophages. XB130 is expressed in alveolar type I and type II cells in the lung. The expression in these cells was significantly reduced after LPS challenge. XB130 deficiency delayed the recovery from systemic septic responses, and the presence of XB130 in the alveolar epithelial cells may provide protective mechanisms by reducing cell death and promoting cell proliferation, and reducing pulmonary permeability. PMID:27029000

  13. [Ventilation in acute respiratory distress. Lung-protective strategies].

    Science.gov (United States)

    Bruells, C S; Rossaint, R; Dembinski, R

    2012-11-01

    Ventilation of patients suffering from acute respiratory distress syndrome (ARDS) with protective ventilator settings is the standard in patient care. Besides the reduction of tidal volumes, the adjustment of a case-related positive end-expiratory pressure and preservation of spontaneous breathing activity at least 48 h after onset is part of this strategy. Bedside techniques have been developed to adapt ventilatory settings to the individual patient and the different stages of ARDS. This article reviews the pathophysiology of ARDS and ventilator-induced lung injury and presents current evidence-based strategies for ventilator settings in ARDS.

  14. Nitrogen dioxide-induced acute lung injury in sheep.

    Science.gov (United States)

    Januszkiewicz, A J; Mayorga, M A

    1994-05-20

    Lung mechanics, hemodynamics and blood chemistries were assessed in sheep (Ovis aries) before, and up to 24 h following, a 15-20 min exposure to either air (control) or approximately 500 ppm nitrogen dioxide (NO2). Histopathologic examinations of lung tissues were performed 24 h after exposure. Nose-only and lung-only routes of exposure were compared for effects on NO2 pathogenesis. Bronchoalveolar lavage fluids from air- and NO2-exposed sheep were analyzed for biochemical and cellular signs of NO2 insult. The influence of breathing pattern on NO2 dose was also assessed. Five hundred ppm NO2 exposure of intubated sheep (lung-only exposure) was marked by a statistically significant, albeit small, blood methemoglobin increase. The exposure induced an immediate tidal volume decrease, and an increase in both breathing rate and inspired minute ventilation. Pulmonary function, indexed by lung resistance and dynamic lung compliance, progressively deteriorated after exposure. Maximal lung resistance and dynamic lung compliance changes occurred at 24 h post exposure, concomitant with arterial hypoxemia. Bronchoalveolar lavage fluid epithelial cell number and total protein were significantly increased while macrophage number was significantly decreased within the 24 h post-exposure period. Histopathologic examination of lung tissue 24 h after NO2 revealed patchy edema, mild hemorrhage and polymorphonuclear and mononuclear leukocyte infiltration. The NO2 toxicologic profile was significantly attenuated when sheep were exposed to the gas through a face mask (nose-only exposure). Respiratory pattern was not significantly altered, lung mechanics changes were minimal, hypoxemia did not occur, and pathologic evidence of exudation was not apparent in nose-only, NO2-exposed sheep. The qualitative responses of this large animal species to high-level NO2 supports the concept of size dependent species sensitivity to NO2. In addition, when inspired minute ventilation was used as a dose

  15. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults

    DEFF Research Database (Denmark)

    Afshari, Arash; Brok, Jesper; Møller, Ann

    2010-01-01

    Acute hypoxaemic respiratory failure (AHRF), defined as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), are critical conditions. AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages. Inhaled nitric oxide (INO) has...

  16. Lung function and bronchial reactivity in farmers.

    Science.gov (United States)

    Iversen, M; Dahl, R; Jensen, E J; Korsgaard, J; Hallas, T

    1989-01-01

    The purpose of this study was to evaluate the prevalence and type of lung function disorders in Danish farmers. Three samples of farmers were drawn from a group of unselected farmers who had participated in an epidemiological study. Group I (47 persons) was a sample of the 8% of all farmers who had reported that they had asthma; group II (63 persons) was a sample of the 28% of farmers who had had wheezing, shortness of breath, or cough without phlegm; and group III (34 persons) a sample of the farmers (64% of the total) who had no asthma and no respiratory symptoms. The farmers with symptoms (groups I and II) had low mean levels of FEV1 and high values for residual volume, whereas the symptomless farmers had normal lung function and no airways obstruction. The proportion of farmers with an FEV1 below the 95% confidence limit for predicted values was 43% in group I and 23% in group II; there were none in group III. Bronchial hyperreactivity to histamine occurred in 96% of asthmatic farmers, 67% of farmers with wheezing or shortness of breath, and 59% of symptomless farmers. A low level of FEV1 was associated with the number of years in pig farming and bronchial hyperreactivity in group II but not group I or III. Most of the bronchial hyperreactivity was explained in the multiple regression analysis by a low FEV1, though this was significant only for farmers in group II. Thus farmers who reported asthma, wheezing, shortness of breath, or a dry cough in general had airways obstruction with an increased residual volume, whereas symptomless farmers had normal lung function. Severe bronchial hyperreactivity was mostly explained by a diagnosis of asthma and poor lung function, though some farmers with normal lung function and no respiratory symptoms had increased bronchial reactivity. PMID:2799744

  17. Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations

    Institute of Scientific and Technical Information of China (English)

    Hsing I Chen

    2011-01-01

    Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can be associated with various disorders.Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALl or ARDS caused by various disorders.This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

  18. Lung function measurement in awake young children

    DEFF Research Database (Denmark)

    Bisgaard, H; Klug, B

    1995-01-01

    The aim of the study was to evaluate methods applicable in a clinical setting for monitoring of changes in lung function in awake young children. Impedance measurements by the impulse oscillation technique (ZIOS), respiratory resistance measurements by the interrupter technique (Rint) and transcu......The aim of the study was to evaluate methods applicable in a clinical setting for monitoring of changes in lung function in awake young children. Impedance measurements by the impulse oscillation technique (ZIOS), respiratory resistance measurements by the interrupter technique (Rint......, with suspected asthma. Measurements with each technique were repeated after each challenge step. A special face-mask was developed with an integrated mouthpiece which ensured mouth breathing during the measurements. The order of sensitivity of the techniques to assess methacholine-induced changes in lung...... to methacholine in young children aged 4-6 yrs. This implies that ZIOS, Rint and Ptc,O2 provide convenient indices of changes in lung function. Their combined use will be useful for monitoring airway diseases of young children....

  19. VEGFA variants are associated with pre-school lung function, but not neonatal lung function

    DEFF Research Database (Denmark)

    Kreiner-Møller, E; Chawes, B L K; Vissing, N H;

    2013-01-01

    Vascular endothelial growth factor (VEGF) is implicated in airway remodelling and asthma development. We studied VEGFA gene variants and plasma levels and the development of lung function, bronchial hyperresponsiveness and asthma in childhood....

  20. Protective effects of penehyclidine hydrochloride on acute lung injury caused by severe dichlorvos poisoning in swine

    Institute of Scientific and Technical Information of China (English)

    CUI Juan; LI Chun-sheng; HE Xin-hua; SONG Yu-guo

    2013-01-01

    Background Organophosphate poisoning is an important health problem in developing countries which causes death mainly by inducing acute lung injury.In this study,we examined the effects of penehyclidine hydrochloride (PHC),a selective M-receptor inhibitor,on dichlorvos-induced acute lung injury in swine.Methods Twenty-two female swines were randomly divided into control (n=5),dichlorvos (n=6),atropine (n=6),and PHC (n=5) groups.Hemodynamic data,extravascular lung water index (EVLWI),and pulmonary vascular permeability index (PVPI) were monitored; blood gas analysis and acetylcholinesterase (AchE) levels were measured.PaO2/FiO2,cardiac index (Cl),and pulmonary vascular resistance indices (PVRI) were calculated.At termination of the study,pulmonary tissue was collected for ATPase activity determination and wet to dry weight ratio (W/D) testing 6 hours post-poisoning.TUNEL assay,and Bax,Bcl-2,and caspase-3 expression were applied to pulmonary tissue,and histopathology was observed.Results After poisoning,PHC markedly decreased PVRI,increased CI more effectively than atropine.Anticholinergic treatment reduced W/D,apoptosis index (AI),and mitigated injury to the structure of lung; however,PHC reduced AI and caspase-3 expression and improved Bcl-2/Bax more effectively than atropine.Atropine and PHC improved ATPase activities; a significant difference between groups was observed in Ca2+-ATPase activity,but not Na+-K+-ATPase activity.Conclusions The PHC group showed mild impairment in pathology,less apoptotic cells,and little impact on cardiac function compared with the atropine group in dichlorvos-induced acute lung injury.

  1. Microcirculation disturbance affects rats with acute severe pancreatitis following lung injury

    Institute of Scientific and Technical Information of China (English)

    Xue-Min Liu; Qing-Guang Liu; Jun Xu; Cheng-En Pan

    2005-01-01

    AIM: To study the effects of microcirculation disturbance(MD) on rats with acute severe pancreatitis (ASP).METHODS: We developed ASP rat models, and anatomized separately after 1, 3, 5, 7, and 9 h. We took out blood and did hemorrheologic examination and erythrocyte osmotic fragility test, checked up the water content, capillary permeability, and genetic expression of intercellular adhesion molecule-1 (ICAM-1) in lung tissues, examined the apoptosis degree of blood vessel endothelium while we tested related gene expression of Bax and Bcl-2in lung tissues. We did the same examination in control group.RESULTS: The viscosity of total blood and plasma, the hematocrit, and the erythrocyte osmotic fragility were all increased. Fibrinogen was decreased. The water content in lung tissues and capillary permeability were increased.Apoptosis degree of blood vessel endothelium was increased too. ICAM-1 genetic expression moved up after1 h and reached its peak value after 9 h.CONCLUSION: MD plays an important role in ASP following acute lung injury (ALI). The functional damage of blood vessel endothelium, the apoptosis of capillary vessel endothelium, WBC edging-concentration and the increasing of erythrocyte fragility are the main reasons of ALI.

  2. A novel, stable and reproducible acute lung injury model induced by oleic acid in immature piglet

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; LING Feng; ZHANG Yan-bo; LIU Ai-jun; LIU Dong-hai; QIAO Chen-hui; WANG Qiang; LIU Ying-long

    2011-01-01

    Background Young children are susceptible to pulmonary injury,and acute lung injury (ALl) often results in a high mortality and financial costs in pediatric patients.A good ALl model will help us to gain a better understanding of the real pathophysiological picture and to evaluate novel treatment approaches to acute respiratory distress syndrome (ARDS) more accurately and liberally.This study aimed to establish a hemodynamically stable and reproducible model with ALl in piglet induced by oleic acid.Methods Six Chinese mini-piglets were used to establish ALl models by oleic acid.Hemodynamic and pulmonary function data were measured.Histopathological assessment was performed.Results Mean blood pressure,heart rate (HR),cardiac output (CO),central venous pressure (CVP) and left atrial pressure (LAP) were sharply decreased after oleic acid given,while the mean pulmonary arterial pressure (MPAP) was increased in comparison with baseline (P <0.05).pH,arterial partial pressure of O2 (PaO2),PaO2/inspired O2 fraction (FiO2) and lung compliance decreased,while PaCO2 and airway pressure increased in comparison with baseline (P <0.05).The lung histology showed severe inflammation,hyaline membranes,intra-alveolar and interstitial hemorrhage.Conclusion This experiment established a stable model which allows for a diversity of studies on early lung injury.

  3. Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats.

    Science.gov (United States)

    Shi, Xianbao; Sun, Hongzhi; Zhou, Dun; Xi, Huanjiu; Shan, Lina

    2015-04-01

    Arctigenin (ATG) has been reported to possess anti-inflammatory properties. However, the effects of ATG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. In the present study, our investigation was designed to reveal the effect of ATG on LPS-induced ALI in rats. We found that ATG pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-1 (IL-6) in the bronchoalveolar lavage fluid. Furthermore, ATG downregulated the expression of nuclear factor kappa B (NF-κB) p65, promoted the phosphorylation of inhibitor of nuclear factor-κB-α (IκBα) and activated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPKα) in the lung tissues. Our results suggested that ATG attenuates the LPS-induced ALI via activation of AMPK and suppression of NF-κB signaling pathway.

  4. Acute lung injury | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction(HARP 2) A.3.1Tit...ical condition(s) being investigated Acute lung injury E.1.1.1Medical condition in easily understood languag...eclined to onset is defined as follows: th

  5. Lung function changes in wildland firefighters working at prescribed burns.

    Energy Technology Data Exchange (ETDEWEB)

    Adetona, Olorunfemi; Hall, Daniel, B.; Naeher, L,P.

    2011-10-01

    Although decline in lung function across workshift has been observed in wildland firefighters, measurements have been restricted to days when they worked at fires. Consequently, such results could have been confounded by normal circadian variation associated with lung function. We investigated the across-shift changes in lung function of wildland firefighters, and the effect of cumulative exposure on lung function during the burn season.

  6. Involvement of phosphoinositide 3-kinases in neutrophil activation and the development of acute lung injury.

    Science.gov (United States)

    Yum, H K; Arcaroli, J; Kupfner, J; Shenkar, R; Penninger, J M; Sasaki, T; Yang, K Y; Park, J S; Abraham, E

    2001-12-01

    Activated neutrophils contribute to the development and severity of acute lung injury (ALI). Phosphoinositide 3-kinases (PI3-K) and the downstream serine/threonine kinase Akt/protein kinase B have a central role in modulating neutrophil function, including respiratory burst, chemotaxis, and apoptosis. In the present study, we found that exposure of neutrophils to endotoxin resulted in phosphorylation of Akt, activation of NF-kappaB, and expression of the proinflammatory cytokines IL-1beta and TNF-alpha through PI3-K-dependent pathways. In vivo, endotoxin administration to mice resulted in activation of PI3-K and Akt in neutrophils that accumulated in the lungs. The severity of endotoxemia-induced ALI was significantly diminished in mice lacking the p110gamma catalytic subunit of PI3-K. In PI3-Kgamma(-/-) mice, lung edema, neutrophil recruitment, nuclear translocation of NF-kappaB, and pulmonary levels of IL-1beta and TNF-alpha were significantly lower after endotoxemia as compared with PI3-Kgamma(+/+) controls. Among neutrophils that did accumulate in the lungs of the PI3-Kgamma(-/-) mice after endotoxin administration, activation of NF-kappaB and expression of proinflammatory cytokines was diminished compared with levels present in lung neutrophils from PI3-Kgamma(+/+) mice. These results show that PI3-K, and particularly PI3-Kgamma, occupies a central position in regulating endotoxin-induced neutrophil activation, including that involved in ALI.

  7. Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction

    Directory of Open Access Journals (Sweden)

    M.F.R. Silva

    1998-03-01

    Full Text Available Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight 24 h before the experiment. Static pressure-volume (PV curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P<0.05, ANOVA, sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation

  8. Lung function abnormalities in children with type I diabetes

    NARCIS (Netherlands)

    van Gent, R; Brackel, HJL; de Vroede, M; van der Ent, CK

    2002-01-01

    Recent developments in intrabronchial administration of insulin raise lung function in patients with type I diabetes as important issue. Several studies in adults report abnormalities of lung function of these patients, The aim of this study was to investigate lung function in children with type I d

  9. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression...... of rat MIP-1 alpha. The resulting product shared 92% and 90% homology with the known murine sequence at the cDNA level and protein level, respectively. Recombinant rat MIP-1 alpha exhibited dose-dependent chemotactic activity for both rat and human monocytes and neutrophils, which could be blocked...... by anti-murine MIP-1 alpha Ab. Rat MIP-1 alpha mRNA and protein expression were determined as a function of time in both injury models. A time-dependent increase in MIP-1 alpha mRNA in lung extracts was observed in both models. In the LPS model, MIP-1 alpha protein could also be detected...

  10. Lung function: occupational exposure to wood dust

    Directory of Open Access Journals (Sweden)

    Baran S

    2009-12-01

    Full Text Available Abstract Objectives Occupational exposure to wood dust has been shown to cause several respiratory disorders, such as allergic rhinitis, chronic bronchitis, asthma, sino-nasal adenocarcinoma, and impairment of lung function. The aim of the study was to estimate lung function (in the woodworking industry among workers employed by wood processing, who run the risk of being expose to wood dust. Methods The study concerns a group of 70 workers aged 24-55. All the workers underwent general and laryngological examination. A group of 20 workers, working at the positions where dustiness exceeded TLV (threshold limit value took X-ray of the chest and spirometry. The following parameters were measured: VC, IC, ERV, TV, BF, FEV1, FVC, PEF, MEF25-75, FEV1%FVC, FEV1%VC. The data are presented as means ± SD and the authors applied references values according to ERS guidelines. Results The results show that there was no decline in FEV1 (3.7 ± 0.7 and FVC (4.5 ± 0.8. Normal lung function was defined as FEV1/VC ratio ≥0.7. None of the tested workers had obstructive pattern in spirometry. The mean FEV1%VC was 77.1 ± 10.2. These results suggest that wood dust exposure might not lead to significant pulmonary damage. Conclusions These data do not corroborate that wood dust plays significant role in lung function impairment. Future studies of respiratory health among workers exposed to wood dust are needed.

  11. Melatonin reduces acute lung injury in endotoxemic rats

    Institute of Scientific and Technical Information of China (English)

    SHANG You; XU San-peng; WU Yan; JIANG Yuan-xu; WU Zhou-yang; YUAN Shi-ying; YAO Shang-long

    2009-01-01

    Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia.Methods Thirty-two male Sprague-Dawley rats were randomly assigned to four groups: vehicle + saline group, melatonin + saline group, vehicle + lipopolysaccharide group, melatonin + lipopolysaccharide group. The rats were treated with melatonin (10 mg/kg, intraperitoneal injection (I.p.)) or vehicle (1% ethanol saline), 30 minutes prior to lipopolysaccharide administration (6 mg/kg, intravenous injection). Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios (W/D), myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha (TNF-a) and interleukin-10 (IL-10) levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B (NF-KB) p65 was evaluated by Western blotting. Results PaO2 in the vehicle + lipopolysaccharide group decreased compared with that in the vehicle + saline group. This decrease was significantly reduced in the melatonin + lipopolysaccharide group. The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin + lipopolysaccharide group. The W/D ratio increased significantly in the vehicle + lipopolysaccharide group (6.1±0.18) as compared with that in the vehicle + saline group (3.611±0.3) (P <0.01), which was significantly reduced in the melatonin + lipopolysaccharide group (4.8±0.25) (P <0.01). Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle + lipopolysaccharide group compared with that in the vehicle + saline group, which

  12. Biomarkers of acute lung injury: worth their salt?

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G

    2011-12-01

    Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

  13. Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    XU Yu-lin; LIU Ying-long; WANG Qiang; LI Gang; L(U) Xiao-dong; KONG Bo

    2012-01-01

    Background Acute lung injury (ALI) and end-stage acute respiratory distress syndrome (ARDS) were among the most common causes of death in intensive care units.The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS.Recent studies had demonstrated the importance of mesenchymal stem cells (MSCs) in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury.Here,our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS.Methods Bone marrow derived MSCs were obtained from Sprague-Dawley (SD) rats and their differential potential was verified.ALl was induced in rats byoleic acid (OA),and MSCs were transplanted intravenously.The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours,24 hours and 48 hours after OA-injection.Results The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs.The concentration of tumor necrosis factor-α and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs,whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours,24 hours and 48 hours after OA-challenge.Conclusions Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS.Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.

  14. Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of exogenous erythropoietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholateinduced acute necrotizing pancreatitis (ANP).METHODS: Forty-seven male Wistar albino rats were randomly divided into 7 groups: sham group (n = 5),3 ANP groups (n = 7 each) and 3 EPO groups (n = 7each). ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct.Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-α, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored.RESULTS: The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-α (TNF-α)and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters after exogenous EPO administration, particularly at 48 h and 72 h.CONCLUSION: EPO administration leads to a significant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation,decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore, can be

  15. Ligustrazine alleviates acute lung injury in a rat model of acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jian-Xin Zhang; Sheng-Chun Dang

    2006-01-01

    BACKGROUND:Acute necrotizing pancreatitis leads to a systemic inlfammatory response characterized by widespread leukocyte activation and, as a consequence, distant lung injury. The aim of this study was to evaluate the effect of ligustrazine, extracted from Ligusticum wallichii a traditional Chinese medicine, on lung injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS:A total of 192 rats were randomly divided into three groups: control (C group); ANP without treatment (P group); and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6 and 12 hours subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. For the T group, sodium taurocholate was infused as above, then 0.6%ligustrazine was administered via the femoral vein. The effects of ligustrazine on the severity of lung injury were assessed by lung wet/dry weight ratio, myeloperoxidase (MPO) activity and histopathological changes. Pulmonary blood lfow was determined by the radioactive microsphere technique (RMT). RESULTS:The blood lfow in the P group was signiifcantly lower than that of the C group, while the blood lfow in the T group was signiifcantly higher than that of the P group but showed no signiifcant difference from the C group. Compared with C group, the lung wet/dry ratios in both the P and T groups were signiifcantly increased, but there was no signiifcant difference between them. The MPO activity in the P group was greatly increased over that of the C group. In the T group, although the MPO activity was also higher than in the C group, it much less increased than in the P group. Moreover, the difference between P and T groups was signiifcant after 0.5 to 12 hours. After induction of the ANP model, the pancreas showed mild edema and congestion;the longer the time, the more severe this became. The pulmonary pathological changes were

  16. Acute Lung Injury | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available rnedUK - MHRA A.2EudraCT number2010-021186-70 A.3Full title of the trial Keratinocyte growth factor in Acute...reviated title of the trial where available Keratinocyte Growth Factor in Acute L...nder investigation E.1.1Medical condition(s) being investigated Acute Lung Injury

  17. Prenatal and postnatal genetic influence on lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil; Bisgaard, Hans; Bønnelykke, Klaus

    2014-01-01

    function measurement by means of spirometry with the raised-volume thoracoabdominal compression technique and bronchial responsiveness to methacholine challenge were assessed in 411 high-risk newborns from the Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC2000) cohort. Measures were...... of methacholine causing a 20% decrease in lung function [PD20]) and with development from birth to age 7 years (FEV0.5/1, FEF50, and PD15/20). RESULTS: The genetic risk scores were not associated with lung function measures at age 1 month, but the FEV1/FVC genetic risk score was associated with reduced FEF50......BACKGROUND: It is unknown to what extent adult lung function genes affect lung function development from birth to childhood. OBJECTIVE: Our aim was to study the association of candidate genetic variants with neonatal lung function and lung function development until age 7 years. METHODS: Lung...

  18. Protective effects of imipramine in murine endotoxin-induced acute lung injury.

    Science.gov (United States)

    Yang, Jin; Qu, Jie-ming; Summah, Hanssa; Zhang, Jin; Zhu, Ying-gang; Jiang, Hong-ni

    2010-07-25

    The tricyclic antidepressant imipramine has recently emerged as a cytoprotective agent, exerting beneficial effects in inflammatory tissue injury. The present study aimed to investigate therapeutic effects of imipramine in murine model of endotoxin-induced acute lung injury. Mice were administrated intraperitoneally with LPS (lipopolysaccharide) from Escherichia coli or vehicle. Imipramine was administrated intraperitoneally 30 min before LPS challenge. Pretreatment of mice with imipramine reduced lethality. Impramine also significantly attenuated lung inflammation, lung edema, MPO (myeloperoxidase) activity, lung tissue pathological changes and nuclear factor-kappaB DNA binding activity. The results of this study suggest that imipramine can exert protective effects in endotoxin-induced acute lung injury by suppressing nuclear factor-kappaB-mediated expression of inflammatory genes. Thus, imipramine could be a potential novel therapeutic agent for the treatment for acute lung injury.

  19. Changes in lung parenchyma after acute respiratory distress syndrome (ARDS): assessment with high-resolution computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Noebauer-Huhmann, I.-M.; Eibenberger, K.; Schaefer-Prokop, C.; Herold, C.J. [Vienna Univ. (Austria). Inst. fuer Radiologie; Steltzer, H.; Strasser, K.; Fridrich, P. [Dept. of General Anesthesia and Intensive Care, Univ. of Vienna (Austria); Schlick, W. [Dept. of Cardio-Thoracic Surgery, Univ. of Vienna (Austria)

    2001-12-01

    The aim of this study was to evaluate the appearance, extent, and distribution of parenchymal changes in the lung after acute respiratory distress syndrome (ARDS) as a function of disease severity and therapeutic procedures. High-resolution computed tomography (HRCT), clinical examination, and lung function tests were performed in 15 patients, 6-10 months after ARDS. The appearance and extent of parenchymal changes were compared with the severity of ARDS, as well as with clinical and therapeutic data. Lung parenchymal changes resembling those found in the presence of pulmonary fibrosis were observed in 13 of 15 patients (87%). The changes were significantly more frequent and more pronounced in the ventral than in the dorsal portions of the lung (p<0.01). A significant correlation was observed between the extent of lung alterations and the severity of ARDS (p<0.01), and the duration in which patients had received mechanical ventilation either with a peak inspiratory pressure greater than 30 mmHg (p<0.05), or with more than 70% oxygen (p<0.01). Acute respiratory distress syndrome frequently is followed by fibrotic changes in lung parenchyma. The predominantly ventral distribution of these changes indicates that they may be caused by the ventilation regimen and the oxygen therapy rather than by the ARDS. (orig.)

  20. Activation of adherent vascular neutrophils in the lung during acute endotoxemia

    Directory of Open Access Journals (Sweden)

    Laskin Jeffrey D

    2002-08-01

    Full Text Available Abstract Background Neutrophils constitute the first line of defense against invading microorganisms. Whereas these cells readily undergo apoptosis under homeostatic conditions, their survival is prolonged during inflammatory reactions and they become biochemically and functionally activated. In the present study, we analyzed the effects of acute endotoxemia on the response of a unique subpopulation of neutrophils tightly adhered to the lung vasculature. Methods Rats were treated with 5 mg/kg lipopolysaccharide (i.v. to induce acute endotoxemia. Adherent neutrophils were isolated from the lung vasculature by collagenase digestion and sequential filtering. Agarose gel electrophoresis, RT-PCR, western blotting and electrophoretic mobility shift assays were used to evaluate neutrophil activity. Results Adherent vascular neutrophils isolated from endotoxemic animals exhibited decreased apoptosis when compared to cells from control animals. This was associated with a marked increase in expression of the anti-apoptotic protein, Mcl-1. Cells isolated 0.5–2 hours after endotoxin administration were more chemotactic than cells from control animals and expressed increased tumor necrosis factor-alpha and cyclooxygenase-2 mRNA and protein, demonstrating that they are functionally activated. Endotoxin treatment of the animals also induced p38 and p44/42 mitogen activated protein kinases in the adherent lung neutrophils, as well as nuclear binding activity of the transcription factors, NF-κB and cAMP response element binding protein. Conclusion These data demonstrate that adherent vascular lung neutrophils are highly responsive to endotoxin and that pathways regulating apoptosis and cellular activation are upregulated in these cells.

  1. Simvastatin reduces endotoxin-induced acute lung injury by decreasing neutrophil recruitment and radical formation.

    Directory of Open Access Journals (Sweden)

    Jochen Grommes

    Full Text Available INTRODUCTION: Treatment of acute lung injury (ALI remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. METHODS: C57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. RESULTS: Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. CONCLUSION: Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

  2. Effects of Ischemic Acute Kidney Injury on Lung Water Balance: Nephrogenic Pulmonary Edema?

    Directory of Open Access Journals (Sweden)

    Rajit K. Basu

    2011-01-01

    Full Text Available Pulmonary edema worsens the morbidity and increases the mortality of critically ill patients. Mechanistically, edema formation in the lung is a result of net flow across the alveolar capillary membrane, dependent on the relationship of hydrostatic and oncotic pressures. Traditionally, the contribution of acute kidney injury (AKI to the formation of pulmonary edema has been attributed to bulk fluid accumulation, increasing capillary hydrostatic pressure and the gradient favoring net flow into the alveolar spaces. Recent research has revealed more subtle, and distant, effects of AKI. In this review we discuss the concept of nephrogenic pulmonary edema. Pro-inflammatory gene upregulation, chemokine over-expression, altered biochemical channel function, and apoptotic dysregulation manifest in the lung are now understood as “extra-renal” and pulmonary effects of AKI. AKI should be counted as a disease process that alters the endothelial integrity of the alveolar capillary barrier and has the potential to overpower the ability of the lung to regulate fluid balance. Nephrogenic pulmonary edema, therefore, is the net effect of fluid accumulation in the lung as a result of both the macroscopic and microscopic effects of AKI.

  3. Critical care in the ED: potentially fatal asthma and acute lung injury syndrome

    Directory of Open Access Journals (Sweden)

    Hodder R

    2012-08-01

    Full Text Available Rick Hodder*Divisions of Pulmonary and Critical Care, University of Ottawa and The Ottawa Hospital, Ottawa, Canada, *Dr Rick Hodder passed away on Tuesday April 17,2012. Please see the Dedication for more information on Dr Hodder.Abstract: Emergency department clinicians are frequently called upon to assess, diagnose, and stabilize patients who present with acute respiratory failure. This review describes a rapid initial approach to acute respiratory failure in adults, illustrated by two common examples: (1 an airway disease – acute potentially fatal asthma, and (2 a pulmonary parenchymal disease – acute lung injury/acute respiratory distress syndrome. As such patients are usually admitted to hospital, discussion will be focused on those initial management aspects most relevant to the emergency department clinician.Keywords: acute asthma, acute lung injury, ARDS, acute respiratory failure

  4. Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Duan Yingli

    2012-01-01

    Full Text Available Abstract Background Proline-rich tyrosine kinase 2 (Pyk2 is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo. Methods C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically. Results Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1 myeloperoxidase content in lung tissues, 2 vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3 the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment. Conclusions These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and

  5. Inhaled aerosolized insulin ameliorates hyperglycemia-induced inflammatory responses in the lungs in an experimental model of acute lung injury

    OpenAIRE

    Fan, Wei; Nakazawa, Koichi; Abe, Shinya; Inoue, Miori; Kitagawa, Masanobu; Nagahara, Noriyuki; Makita, Koshi

    2013-01-01

    Introduction Previous studies have shown that patients with diabetes mellitus appear to have a lower prevalence of acute lung injury. We assumed that insulin prescribed to patients with diabetes has an anti-inflammatory property and pulmonary administration of insulin might exert beneficial effects much more than intravenous administration. Methods Twenty-eight mechanically ventilated rabbits underwent lung injury by saline lavage, and then the animals were allocated into a normoglycemia grou...

  6. Monoacylglycerol lipase (MAGL inhibition attenuates acute lung injury in mice.

    Directory of Open Access Journals (Sweden)

    Carolina Costola-de-Souza

    Full Text Available Endocannabinoid signaling is terminated by enzymatic hydrolysis, a process that, for 2-Arachidonoylglycerol (2-AG, is mediated by monoacylglycerol lipase (MAGL. The piperidine carbamate, 4-nitrophenyl- 4-(dibenzo[d] [1,3]dioxol-5-yl (hydroxy methyl piperidine- 1-carboxylate (JZL184, is a drug that inhibits MAGL and presents high potency and selectivity. Thus, JZL184 increases the levels of 2-AG, an endocannabinoid that acts on the CB1 and CB2 cannabinoid receptors. Here, we investigated the effects of MAGL inhibition, with a single dose (16 mg/kg, intraperitoneally (i.p. of JZL184, in a murine model of lipopolysaccharide (LPS -induced acute lung injury (ALI 6, 24 and 48 hours after the inflammatory insult. Treatment with JZL184 decreased the leukocyte migration into the lungs as well as the vascular permeability measured through the bronchoalveolar lavage fluid (BAL and histological analysis. JZL184 also reduced the cytokine and chemokine levels in the BAL and adhesion molecule expression in the blood and BAL. The CB1 and CB2 receptors were considered involved in the anti-inflammatory effects of JZL184 because the AM281 selective CB1 receptor antagonist (1-(2,4-dichlorophenyl-5-(4-iodophenyl-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide and the AM630 selective CB2 receptor antagonist ([6-iodo-2-methyl-1-[2-(4-morpholinylethyl]-1H-indol-3-yl](4-methoxyphenyl-methanone blocked the anti-inflammatory effects previously described for JZL184. It was concluded that MAGL inhibition, and consequently the increase in 2-AG levels, produced anti-inflammatory effects in a murine model of LPS-induced ALI, a finding that was considered a consequence of the activation of the CB1 and CB2 receptors.

  7. Acute respiratory distress syndrome and lung fibrosis after ingestion of a high dose of ortho-phenylphenol.

    Science.gov (United States)

    Cheng, Shih-Lung; Wang, Hao-Chien; Yang, Pan-Chyr

    2005-08-01

    Ortho-phenylphenol (OPP) and its sodium salt are used as fungicides and antibacterial agents, ingestion of which has been found to cause liver toxicity, renal toxicity and carcinomas in the urinary tract of rats. Lung damage due to OPP ingestion has not been reported in humans. We report a suicidal 39-year-old woman with stage II cervical cancer who drank a potentially lethal dose of OPP in the form of a commercial antiseptic, which led to the complication of liver and renal function impairment, severe lung damage with acute respiratory distress syndrome and subsequent severe lung fibrosis. Open lung biopsy showed diffuse alveolar damage. She was discharged after 34 days of hospitalization with continuing domiciliary oxygen therapy.

  8. Extracorporeal Membrane Oxygenation (ECMO) for Lung Injury in Severe Acute Respiratory Distress Syndrome (ARDS): Review of the Literature.

    Science.gov (United States)

    Paolone, Summer

    2016-11-10

    Despite advances in mechanical ventilation, severe acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality rates ranging from 26% to 58%. Extracorporeal membrane oxygenation (ECMO) is a modified cardiopulmonary bypass circuit that serves as an artificial membrane lung and blood pump to provide gas exchange and systemic perfusion for patients when their own heart and lungs are unable to function adequately. ECMO is a complex network that provides oxygenation and ventilation and allows the lungs to rest and recover from respiratory failure while minimizing iatrogenic ventilator-induced lung injury. In critical care settings, ECMO is proven to improve survival rates and outcomes in patients with severe ARDS. This review defines severe ARDS; describes the ECMO circuit; and discusses recent research, optimal use of the ECMO circuit, limitations of therapy including potential complications, economic impact, and logistical factors; and discusses future research considerations.

  9. Acute onset paraneoplastic cerebellar degeneration in a patient with small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Bhatia R

    2003-04-01

    Full Text Available A patient with small cell lung cancer presented with a rare presentation of an acute onset pancerebellar dysfunction. His clinical condition markedly improved following the surgical removal of the tumor and chemo- and radiotherapy.

  10. Lymphatic function is required prenatally for lung inflation at birth

    Science.gov (United States)

    Jakus, Zoltán; Gleghorn, Jason P.; Enis, David R.; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R.; Yang, Yiqing; Hess, Paul R.; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H.; Nelson, Celeste M.

    2014-01-01

    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants. PMID:24733830

  11. β2 adrenergic agonists in acute lung injury? The heart of the matter

    OpenAIRE

    Lee, Jae W

    2009-01-01

    Despite extensive research into its pathophysiology, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains a devastating syndrome with mortality approaching 40%. Pharmacologic therapies that reduce the severity of lung injury in vivo and in vitro have not yet been translated to effective clinical treatment options, and innovative therapies are needed. Recently, the use of β2 adrenergic agonists as potential therapy has gained considerable interest due to their ability to in...

  12. Increased T cell glucose uptake reflects acute rejection in lung grafts

    OpenAIRE

    Chen, Delphine L.; Wang, Xingan; Yamamoto, Sumiharu; Carpenter, Danielle; Engle, Jacquelyn T.; Li, Wenjun; Lin, Xue; Kreisel, Daniel; Krupnick, Alexander S.; Huang, Howard J.; Gelman, Andrew E.

    2013-01-01

    Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [18F]fluorodeoxyglucose ([18F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the graft...

  13. Two novel mutations in surfactant protein-C, lung function and obstructive lung disease

    DEFF Research Database (Denmark)

    Baekvad-Hansen, Marie; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne;

    2010-01-01

    Dominant mutations in the surfactant protein-C(SFTPC) gene have been linked with interstitial lung disease. The frequency of lung disease due to SFTPC mutations in the general population is unknown. The aim of this study was to identify novel SFTPC mutations that are associated with lung function...... pulmonary disease or interstitial lung disease. No Y106X heterozygotes suffered from asthma, chronic obstructive pulmonary disease (COPD), or interstitial lung disease. We identified two novel mutations in highly conserved areas of the SFTPC gene, and show that heterozygotes for the mutations have normal...... lung function and are unaffected by COPD and interstitial lung disease. A53T heterozygotes had increased asthma risk, but further research is required to conclusively determine whether this mutation is associated with asthma....

  14. Blood transfusion : Transfusion-related acute lung injury: back to basics

    NARCIS (Netherlands)

    Peters, A.L.

    2017-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening disease affecting the lungs. TRALI can develop within 6 hours after transfusion and almost all patients with TRALI require mechanical ventilation at the intensive care department. Nevertheless up to 40% of patients do not recover fr

  15. Protection of lung function by introducing single photon emission computed tomography lung perfusion image into radiotherapy plan of lung cancer

    Institute of Scientific and Technical Information of China (English)

    YIN Yong; CHEN Jin-hu; LI Bao-sheng; LIU Tong-hai; LU jie; BAI Tong; DONG Xiao-ling; YU Jin-ming

    2009-01-01

    Background The lung functional status could be displayed on lung perfusion images. With the images, the radiotherapy plans of lung cancer could be guided to more optimized. This study aimed to assess quantitatively the impact of incorporating functional lung imaging into 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) planning for non-small cell lung cancer (NSCLC).Methods Ten patients with NSCLC who had undergone radiotherapy were included in this study. Before radiotherapy,each patient underwent CT simulation and lung perfusion imaging with single photon emission computed tomography (SPECT). The SPECT images were registered with simulation planning CT and used to contour functional lung (lung-F) and non-functional lung (lung-NF). Two 3DCRT plans and two IMRT plans were designed and compared in each patient:two anatomic plans using simulation CT alone and two functional plans using SPECT-CT in addition to the simulation CT.Dosimetric parameters of the four types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Total radiation dose was set at 66 Gy (2 Gy×33 fractions).Results In incorporating perfusion information in 3DCRT and IMRT planning, the reductions on average in the mean doses to the functional lung in the functional plan were 168 cGy and 89 cGy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, >20 Gy, >30 Gy and >40 Gy for functional lung in the functional plans were 6.50%, 10.21%, 14.02%, 22.30% and 23.46% in 3DCRT planning,respectively, and 3.05%, 15.52%, 14.16%, 4.87%, and 3.33% in IMRT planning, respectively. No greater degree of sparing of the functional lung was achieved in functional IMRT than in 3DCRT.Conclusion Function-guided 3DCRT and IMRT plannings both appear to be effective in preserving functional lung in NSCLC patients.

  16. Lung tissue remodeling in the acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Souza Alba Barros de

    2003-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

  17. Optical and Functional Imaging in Lung Cancer

    NARCIS (Netherlands)

    K.H. van der Leest (Cor)

    2010-01-01

    textabstractLung cancer is the second most common cancer in men and women, and is the leading cause of cancer related death. In industrialized countries the mortality rate of lung cancer is higher than the mortality rate of breast, colorectal and prostate cancer combined 1. When lung cancer is diagn

  18. Protective Effects of Cucurbitacin B on Acute Lung Injury Induced by Sepsis in Rats

    Science.gov (United States)

    Hua, Shu; Liu, Xing; Lv, Shuguang; Wang, Zhifang

    2017-01-01

    Background The aim of this study was to investigate the protective effects of cucurbitacin B (CuB) on sepsis-induced acute lung injury (ALI) in rats. Material/Methods An ALI model was made by cecal ligation and puncture (CLP) in SD rats. Rats were randomly divided into 5 groups (n=15 per group): animals undergoing a sham CLP (sham group); animals undergoing CLP (CLP control group); animals undergoing CLP and treated with CuB at 1 mg/kg of body weight (bw) (low-dose CuB [L-CuB] group), animals undergoing CuB at 2 mg/kg of bw (mid-dose CuB [M-CuB] group); and animals undergoing CuB at 5 mg/kg of bw (high-dose CuB [H-CuB] group). Samples of blood and lung tissue were harvested at different time points (6, 12, and 24 hour post-CLP surgery) for the detection of indicators which represented ALI. Five rats were respectively sacrificed at each time point. Pathological changes of lung tissue were observed by H&E staining. Another 50 rats were distributed into the same five groups to record the 72 hour survival rates. Results Treatment with CuB significantly increased the blood gas PaO2 levels and decreased lung wet/dry (W/D) ratio (ptumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), (pprotection effects in a dose-depended manner. Conclusions CuB can effectively improve the pulmonary gas exchange function, reduce pulmonary edema, and inhibit the inflammatory response in the lung, revealing that CuB may serve as a potential therapeutic strategy for sepsis-induced ALI. PMID:28315572

  19. Amniotic fluid stem cells from EGFP transgenic mice attenuate hyperoxia-induced acute lung injury.

    Directory of Open Access Journals (Sweden)

    Shih-Tao Wen

    Full Text Available High concentrations of oxygen aggravate the severity of lung injury in patients requiring mechanical ventilation. Although mesenchymal stem cells have been shown to effectively attenuate various injured tissues, there is limited information regarding a role for amniotic fluid stem cells (AFSCs in treating acute lung injury. We hypothesized that intravenous delivery of AFSCs would attenuate lung injury in an experimental model of hyperoxia-induced lung injury. AFSCs were isolated from EGFP transgenic mice. The in vitro differentiation, surface markers, and migration of the AFSCs were assessed by specific staining, flow cytometry, and a co-culture system, respectively. The in vivo therapeutic potential of AFSCs was evaluated in a model of acute hyperoxia-induced lung injury in mice. The administration of AFSCs significantly reduced the hyperoxia-induced pulmonary inflammation, as reflected by significant reductions in lung wet/dry ratio, neutrophil counts, and the level of apoptosis, as well as reducing the levels of inflammatory cytokine (IL-1β, IL-6, and TNF-α and early-stage fibrosis in lung tissues. Moreover, EGFP-expressing AFSCs were detected and engrafted into a peripheral lung epithelial cell lineage by fluorescence microscopy and DAPI stain. Intravenous administration of AFSCs may offer a new therapeutic strategy for acute lung injury (ALI, for which efficient treatments are currently unavailable.

  20. Acute Lung Injury and Fibrosis in a Baboon Model of Escherichia coli Sepsis

    Science.gov (United States)

    Keshari, Ravi S.; Silasi-Mansat, Robert; Zhu, Hua; Popescu, Narcis I.; Peer, Glenn; Chaaban, Hala; Lambris, John D.; Polf, Holly; Lupu, Cristina; Kinasewitz, Gary

    2014-01-01

    Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrosis. The pathology of ARDS is complex and poorly understood, and the therapeutic approaches are limited. We used a baboon model of Escherichia coli sepsis that mimics the complexity of human disease to study the pathophysiology of ARDS. We performed extensive biochemical, histological, and functional analyses to characterize the disease progression and the long-term effects of sepsis on the lung structure and function. Similar to humans, sepsis-induced ARDS in baboons displays an early inflammatory exudative phase, with extensive necrosis. This is followed by a regenerative phase dominated by proliferation of type 2 epithelial cells, expression of epithelial-to-mesenchymal transition markers, myofibroblast migration and proliferation, and collagen synthesis. Baboons that survived sepsis showed persistent inflammation and collagen deposition 6–27 months after the acute episodes. Long-term survivors had almost double the amount of collagen in the lung as compared with age-matched control animals. Immunostaining for procollagens showed persistent active collagen synthesis within the fibroblastic foci and interalveolar septa. Fibroblasts expressed markers of transforming growth factor-β and platelet-derived growth factor signaling, suggesting their potential role as mediators of myofibroblast migration and proliferation, and collagen deposition. In parallel, up-regulation of the inhibitors of extracellular proteases supports a deregulated matrix remodeling that may contribute to fibrosis. The primate model of sepsis-induced ARDS mimics the disease progression in humans, including chronic inflammation and long-lasting fibrosis. This model helps our understanding of the pathophysiology of fibrosis and the testing of new therapies. PMID:24066737

  1. Effects of budesonide and N-acetylcysteine on acute lung hyperinflation, inflammation and injury in rats.

    Science.gov (United States)

    Jansson, Anne-Helene; Eriksson, Christina; Wang, Xiangdong

    2005-08-01

    Leukocyte activation and production of inflammatory mediators and reactive oxygen species are important in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. The present study investigated acute lung hyperinflation, edema, and lung inflammation 4 h after an intratracheal instillation of LPS (0.5, 2.5, 5, 10, 50, 100, 500, 1000, and 5000 microg/ml/kg). Effects of budesonide, an inhaled anti-inflammatory corticosteroids, and N-acetylcysteine (NAC), an antioxidant, were evaluated in Wistar rats receiving either low (2.5 microg/ml/kg) or high (50 microg/ml/kg) concentrations of LPS. This study demonstrates that LPS in a concentration-dependent pattern induces acute lung hyperinflation measured by excised lung gas volume (25-45% above control), lung injury indicated by increased lung weight (10-60%), and lung inflammation characterized by the infiltration of leukocytes (40-14000%) and neutrophils (80-17000%) and the production of cytokines (up to 2700%) and chemokines (up to 350%) in bronchoalveolar lavage fluid (BALF). Pretreatment with NAC partially prevented tumor necrosis factor alpha (TNFalpha) production induced by the low concentration of LPS, while pretreatment with budesonide totally prevented the increased production of TNFalpha, interleukin (IL)-1beta, IL-6, and monocyte chemoattractive protein (MCP)-1 after LPS challenge at both low and high concentrations. Budesonide failed to prevent BALF levels of macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant 1 (GRO/CINC-1) as well as lung hyperinflation induced by both low and high concentrations of LPS. Pretreatment with budesonide totally prevented the formation of lung edema at the low concentration of LPS and had partial effects on acute lung injury and leukocyte influx at the high concentrations. Thus, our data indicate that therapeutic effects of budesonide and NAC are dependent upon the severity of the disease.

  2. Acute lung injury in children : from viral infection and mechanical ventilation to inflammation and apoptosis

    NARCIS (Netherlands)

    Bern, R.A.

    2010-01-01

    Acute lung injury (ALI), ook bekend als acute respiratory distress syndrome (ARDS), is een uitgebreide ontstekingsreactie in beide longen door een longziekte of een aandoening elders in het lichaam. Kinderen lijken minder gevoelig voor de ziekte dan volwassenen, wellicht door de manier waarop de lon

  3. Early preventive treatment for severe acute pancreatitis combined with lung injury

    Institute of Scientific and Technical Information of China (English)

    刘学民; 刘青光; 潘承恩

    2002-01-01

    @@ Severe acute pancreatitis (SAP) can cause systematic inflammatory response syndrome (SIRS),which leads to injury or failure of the internal organs and systems.1 Among them,acute respiratory distress syndrome(ARDS)is a severe or fatal complication.In this article,the early preventive treatment for SAP combined with lung injure is studied.

  4. EXPRESSION OF INTERCELLULAR ADHESION MOLECULE IN LUNG TISSUES OF EXPERIMENTAL ACUTE LUNG INJURY AND THE AFFECT OF RHUBARB ON IT

    Institute of Scientific and Technical Information of China (English)

    李春盛; 桂培春; 何新华

    2000-01-01

    Objeaive. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. Methods. Lipopolysaeeharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasoue group.Macroscopic and histopathological e~aminatiom were performed and biological markers were measured for the lung specimem. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA. Results. In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P < 0.01),demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasoue and rhubarb emfld decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P< 0.01, P < 0.05) ; the correslxmding pathologic changes of lung tissues and the biological markers of the lung injury were simifieantlv decreased or ameliorated. Conclusions. The increase of the expression d ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI.The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM-1 m

  5. EXPRESSION OF INTERCELLULAR ADHESION MOLECULE IN LUNG TISSUES OF EXPERIMENTAL ACUTE LUNG INJURY AND THE AFFECT OF RHUBARB ON IT

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury.Methods. Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA.Results. In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P<0.01), demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P<0.01, P<0.05); the corresponding pathologic changes of lung tissues and the biological markers of the lung injury were significantly decreased or ameliorated.Conclusions. The increase of the expression of ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM

  6. Changes in the bacterial microbiota in gut, blood, and lungs following acute LPS instillation into mice lungs.

    Directory of Open Access Journals (Sweden)

    Marc A Sze

    Full Text Available Previous reports have shown that the gastrointestinal (GI bacterial microbiota can have profound effects on the lungs, which has been described as the "gut-lung axis". However, whether a "lung-gut" axis exists wherein acute lung inflammation perturbs the gut and blood microbiota is unknown.Adult C57/Bl6 mice were exposed to one dose of LPS or PBS instillation (n=3 for each group directly into lungs. Bacterial microbiota of the bronchoalveolar lavage fluid, blood, and cecum were determined using 454 pyrotag sequencing and quantitative polymerase chain reaction (qPCR at 4 through 168 hours post-instillation. We then investigated the effects of oral neomycin and streptomycin (n=8 on the microbiota at 4 and 24 hours post LPS instillation versus control treatment (n=5 at baseline and 4 hours, n=7 at 24 hours.At 24 hours post LPS instillation, the total bacterial count was significantly increased in the cecum (P<0.05; whereas the total bacterial count in blood was increased at 4, 48, and 72 hours (P<0.05. Antibiotic treatment reduced the total bacteria in blood but not in the cecum. The increase in total bacteria in the blood correlated with Phyllobacteriaceae OTU 40 and was significantly reduced in the blood for both antibiotic groups (P<0.05.LPS instillation in lungs leads to acute changes in the bacterial microbiota in the blood and cecum, which can be modulated with antibiotics.

  7. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    Energy Technology Data Exchange (ETDEWEB)

    Ninaber, Maarten K., E-mail: m.k.ninaber@lumc.nl [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Stolk, Jan; Smit, Jasper; Le Roy, Ernest J. [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Kroft, Lucia J.M. [Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Els Bakker, M. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Vries Bouwstra, Jeska K. de; Schouffoer, Anne A. [Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Staring, Marius; Stoel, Berend C. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands)

    2015-05-15

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

  8. Increased T cell glucose uptake reflects acute rejection in lung grafts

    Science.gov (United States)

    Chen, Delphine L.; Wang, Xingan; Yamamoto, Sumiharu; Carpenter, Danielle; Engle, Jacquelyn T.; Li, Wenjun; Lin, Xue; Kreisel, Daniel; Krupnick, Alexander S.; Huang, Howard J.; Gelman, Andrew E.

    2013-01-01

    Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [18F]fluorodeoxyglucose ([18F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the grafts of syngeneic and allogeneic recipients with or without immunosuppression treatment. Pulmonary microPET scans demonstrated significantly higher [18F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [18F]FDG uptake was also markedly attenuated following T cell depletion therapy in lung recipients with ongoing acute rejection. Flow-cytometric analysis using the fluorescent deoxyglucose analog 2-NBDG revealed that T cells, and in particular CD8+ T cells, were the largest glucose utilizers in acutely rejecting lung grafts followed by neutrophils and antigen presenting cells. These data indicate that imaging modalities tailored toward assessing T cell metabolism may be useful in identifying acute rejection in lung recipients PMID:23927673

  9. The value of nitrogen washout/washin method in assessing alveolar recruitment volume in acute lung injury patients

    Institute of Scientific and Technical Information of China (English)

    李洋

    2013-01-01

    Objective To evaluate the precision and feasibility of nitrogen washout/washin method in assessing lung recruitment of acute lung injury(ALI)patients.Methods Fifteen ALI patients underwent mechanical ventilation

  10. [Lung ultrasound in acute and critical care medicine].

    Science.gov (United States)

    Zechner, P M; Seibel, A; Aichinger, G; Steigerwald, M; Dorr, K; Scheiermann, P; Schellhaas, S; Cuca, C; Breitkreutz, R

    2012-07-01

    The development of modern critical care lung ultrasound is based on the classical representation of anatomical structures and the need for the assessment of specific sonography artefacts and phenomena. The air and fluid content of the lungs is interpreted using few typical artefacts and phenomena, with which the most important differential diagnoses can be made. According to a recent international consensus conference these include lung sliding, lung pulse, B-lines, lung point, reverberation artefacts, subpleural consolidations and intrapleural fluid collections. An increased number of B-lines is an unspecific sign for an increased quantity of fluid in the lungs resembling interstitial syndromes, for example in the case of cardiogenic pulmonary edema or lung contusion. In the diagnosis of interstitial syndromes lung ultrasound provides higher diagnostic accuracy (95%) than auscultation (55%) and chest radiography (72%). Diagnosis of pneumonia and pulmonary embolism can be achieved at the bedside by evaluating subpleural lung consolidations. Detection of lung sliding can help to detect asymmetrical ventilation and allows the exclusion of a pneumothorax. Ultrasound-based diagnosis of pneumothorax is superior to supine anterior chest radiography: for ultrasound the sensitivity is 92-100% and the specificity 91-100%. For the diagnosis of pneumothorax a simple algorithm was therefore designed: in the presence of lung sliding, lung pulse or B-lines, pneumothorax can be ruled out, in contrast a positive lung point is a highly specific sign of the presence of pneumothorax. Furthermore, lung ultrasound allows not only diagnosis of pleural effusion with significantly higher sensitivity than chest x-ray but also visual control in ultrasound-guided thoracocentesis.

  11. Interaction between asthma and lung function growth in early life

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Jensen, Signe Marie; Bønnelykke, Klaus

    2012-01-01

    The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma.......The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma....

  12. MARESIN 1 PREVENTS LIPOPOLYSACCHARIDE-INDUCED NEUTROPHIL SURVIVAL AND ACCELERATES RESOLUTION OF ACUTE LUNG INJURY.

    Science.gov (United States)

    Gong, Jie; Liu, Hong; Wu, Jing; Qi, Hong; Wu, Zhou-Yang; Shu, Hua-Qing; Li, Hong-Bin; Chen, Lin; Wang, Ya-Xin; Li, Bo; Tang, Min; Ji, Yu-Dong; Yuan, Shi-Ying; Yao, Shang-Long; Shang, You

    2015-10-01

    Acute lung injury (ALI) is characterized by lung inflammation and diffuse infiltration of neutrophils. Neutrophil apoptosis is recognized as an important control point in the resolution of inflammation. Maresin 1 (MaR1) is a new docosahexaenoic acid-derived proresolving agent that promotes the resolution of inflammation. However, its function in neutrophil apoptosis is unknown. In this study, isolated human neutrophils were incubated with MaR1, the pan-caspase inhibitor z-VAD-fmk, and lipopolysaccharide (LPS) to determine the mechanism of neutrophil apoptosis. Acute lung injury was induced by intratracheal instillation of LPS. In addition, mice were treated with MaR1 intravenously at the peak of inflammation and administered z-VAD-fmk intraperitoneally. We found that culture of isolated human neutrophils with LPS dramatically delayed neutrophil apoptosis through the phosphorylation of AKT, ERK, and p38 to upregulate the expression of the antiapoptotic proteins Mcl-1 and Bcl-2, which was blocked by pretreatment with MaR1 in vitro. In mice, MaR1 accelerated the resolution of inflammation in LPS-induced ALI through attenuation of neutrophil accumulation, pathohistological changes, and pulmonary edema. Maresin 1 promoted resolution of inflammation by accelerating caspase-dependent neutrophil apoptosis. Moreover, MaR1 also reduced the LPS-induced production of proinflammatory cytokines and upregulated the production of the anti-inflammatory cytokine interleukin-10. In contrast, treatment with z-VAD-fmk inhibited the proapoptotic action of MaR1 and attenuated the protective effects of MaR1 in LPS-induced ALI. Taken together, MaR1 promotes the resolution of LPS-induced ALI by overcoming LPS-mediated suppression of neutrophil apoptosis.

  13. [Portable lung function parameters testing system based on DSP].

    Science.gov (United States)

    Guo, Zhanshe; Yuan, Minzhong; Zhou, Hui

    2012-11-01

    Lung function monitoring is a critical technique for clinical medicine. Currently, the lung function testing devices used in our domestic hospitals are both expensive and bulky. A portable and accurate lung function parameters testing system is highly desired and is proposed in this paper. The hardware of the system is based on DSP technology. The breathing passage is designed with an aim suitable for the breathe and signal detection. We use the direct detection method to detect the gas flow, the breathing passage pressure and the breathing time. Thanks to the powerful data processing ability and the high operation speed of the DSP, breathing signals can be easily analyzed. Thus, several lung function parameters of clinical significance can be obtained. Experiments show that the accuracy of the system is better than 3%, and could meet the demand of the lung function testing.

  14. Protective effect of ulinastatin on acute lung injury after radiotherapy in patients with lung cancer and the related molecular mechanism

    Institute of Scientific and Technical Information of China (English)

    Guang-Ping Fan

    2016-01-01

    Objective:To analyze the protective effect of ulinastatin on acute lung injury after radiotherapy in patients with lung cancer and the related molecular mechanism.Methods:A total of 78 patients who received radiotherapy and developed acute lung injury in our hospital between December 2013 and December 2015 were randomly divided into observation group and control group, control group received symptomatic treatment, observation group received symptomatic + ulinastatin treatment, and the content of growth factors, inflammatory factors, disease-related proteins in serum as well as the expression of P38MAPK signaling pathway molecules in alveolar lavage fluid were compared between two groups of patients after treatment.Results:Ten days after treatment, HGF, KGF, VEGF, IL-1β, IL-8, IL-10, IL-18, IL-13, PCT, S100A8, S100A9 and SP-D content in serum of observation group were significantly lower than those of control group while Clara cell protein content was significantly higher than that of control group; phosphorylated p38MAPK, MAPK, MKK3/6 and ATF-2 protein expression levels in alveolar lavage fluid were significantly lower than those of control group.Conclusions:Ulinastatin can alleviate the overall condition in patients with acute lung injury after radiotherapy, and the specific mechanism is associated with P38MAPK signaling pathway.

  15. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid.

    Science.gov (United States)

    Fisher, Bernard J; Kraskauskas, Donatas; Martin, Erika J; Farkas, Daniela; Wegelin, Jacob A; Brophy, Donald; Ward, Kevin R; Voelkel, Norbert F; Fowler, Alpha A; Natarajan, Ramesh

    2012-07-01

    Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

  16. Metabolic Functions of the Lung, Disorders and Associated Pathologies.

    Science.gov (United States)

    Alvarado, Alcibey; Arce, Isabel

    2016-10-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth's atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration.

  17. Partial liquid ventilation improves lung function in ventilation-induced lung injury

    NARCIS (Netherlands)

    G.F. Vazquez de Anda; R.A. Lachmann; S.J.C. Verbrugge (Serge); D.A.M.P.J. Gommers (Diederik); J.J. Haitsma (Jack); B.F. Lachmann (Burkhard)

    2001-01-01

    textabstractDisturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish l

  18. Diagnostic and Therapeutic Aspects of Acute Lung Injury: empirical studies

    NARCIS (Netherlands)

    R.A. Lachmann

    2006-01-01

    textabstractThe thesis emphases research on prognostic markers as well as on different approaches for treating lung injury. Thereby, the prevention and treatment of pneumonia and possible ventilation induced bacterial translocation from the lung into the blood represents the main focus of th

  19. Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury.

    Science.gov (United States)

    Abraham, E; Carmody, A; Shenkar, R; Arcaroli, J

    2000-12-01

    Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-kappaB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1beta (IL-1beta), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1beta, MIP-2, and TNF-alpha were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1beta and MIP-2 but not in TNF-alpha expression in the lungs after endotoxemia. These experiments show that neutrophils play a central role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.

  20. Correlation of apical fluid-regulating channel proteins with lung function in human COPD lungs.

    Directory of Open Access Journals (Sweden)

    Runzhen Zhao

    Full Text Available Links between epithelial ion channels and chronic obstructive pulmonary diseases (COPD are emerging through animal model and in vitro studies. However, clinical correlations between fluid-regulating channel proteins and lung function in COPD remain to be elucidated. To quantitatively measure epithelial sodium channels (ENaC, cystic fibrosis transmembrane conductance regulator (CFTR, and aquaporin 5 (AQP5 proteins in human COPD lungs and to analyze the correlation with declining lung function, quantitative western blots were used. Spearman tests were performed to identify correlations between channel proteins and lung function. The expression of α and β ENaC subunits was augmented and inversely associated with lung function. In contrast, both total and alveolar type I (ATI and II (ATII-specific CFTR proteins were reduced. The expression level of CFTR proteins was associated with FEV1 positively. Abundance of AQP5 proteins and extracellular superoxide dismutase (SOD3 was decreased and correlated with spirometry test results and gas exchange positively. Furthermore, these channel proteins were significantly associated with severity of disease. Our study demonstrates that expression of ENaC, AQP5, and CFTR proteins in human COPD lungs is quantitatively associated with lung function and severity of COPD. These apically located fluid-regulating channels may thereby serve as biomarkers and potent druggable targets of COPD.

  1. beta2 adrenergic agonists in acute lung injury? The heart of the matter.

    Science.gov (United States)

    Lee, Jae W

    2009-01-01

    Despite extensive research into its pathophysiology, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains a devastating syndrome with mortality approaching 40%. Pharmacologic therapies that reduce the severity of lung injury in vivo and in vitro have not yet been translated to effective clinical treatment options, and innovative therapies are needed. Recently, the use of beta2 adrenergic agonists as potential therapy has gained considerable interest due to their ability to increase the resolution of pulmonary edema. However, the results of clinical trials of beta agonist therapy for ALI/ARDS have been conflicting in terms of benefit. In the previous issue of Critical Care, Briot and colleagues present evidence that may help clarify the inconsistent results. The authors demonstrate that, in oleic acid lung injury in dogs, the inotropic effect of beta agonists may recruit damaged pulmonary capillaries, leading to increased lung endothelial permeability.

  2. Dicer function is essential for lung epithelium morphogenesis.

    Science.gov (United States)

    Harris, Kelley S; Zhang, Zhen; McManus, Michael T; Harfe, Brian D; Sun, Xin

    2006-02-14

    DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only a single Dicer gene exists in the mouse genome, and it is broadly expressed in developing tissues. Dicer-null mutants die before gastrulation. Therefore, to study Dicer function in the later event of lung formation, we inactivated it in the mouse lung epithelium using a Dicer conditional allele and the Sonic Hedgehogcre (Shhcre) allele. Branching arrests in these mutant lungs, although epithelial growth continues in distal domains that are expanded compared with normal samples. These defects result in a few large epithelial pouches in the mutant lung instead of numerous fine branches present in a normal lung. Significantly, the initial phenotypes are apparent before an increase in epithelial cell death is observed, leading us to propose that Dicer plays a specific role in regulating lung epithelial morphogenesis independent of its requirement in cell survival. In addition, we found that the expression of Fgf10, a key gene involved in lung development, is up-regulated and expanded in the mesenchyme of Dicer mutant lungs. Previous studies support the hypothesis that precise localization of FGF10 in discrete sites of the lung mesenchyme serves as a chemoattractant for the outgrowth of epithelial branches. The aberrant Fgf10 expression may contribute to the Dicer morphological defects. However, the mechanism by which DICER functions in the epithelium to influence Fgf10 expression in the mesenchyme remains unknown.

  3. First-pass studies of acute lung injury.

    Science.gov (United States)

    Chu, R Y; Sidhu, N; Basmadjian, G; Burow, R; Allen, E W

    1993-10-01

    Mild hydrochloric acid was introduced to a caudal lung section in each of eight dogs to induce injury. Transits of 99mTc-labeled red blood cells (RBC) and [123I]iodoantipyrine (IAP) injected intravenously were recorded by a scintillation camera. Lungs and blood samples were analyzed post-mortem. Peak-to-equilibrium ratios (P/E) of RBC time-activity curves were computed to be 3.83 +/- 0.54 for the control lung, 2.58 +/- 0.55 for the injured lung and 2.23 +/- 0.58 for the injured caudal section. For IAP, the respective results were 3.78 +/- 0.29, 2.02 +/- 0.18 and 1.77 +/- 0.17. The decrease of P/E in injured areas was attributed to reduced blood flow. Using mean transit times of the tracers, we computed extravascular lung water per unit blood volume to be 0.35 +/- 0.18 for the control lungs and an increased value of 0.68 +/- 0.24 for the injured lungs. These results displayed sensitivity to injury, but were gross underestimates relative to the corresponding values of 2.04 +/- 0.54 and 4.56 +/- 1.85 in post-mortem analyses.

  4. First-pass studies of acute lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Chu, R.Y.L.; Sidhu, N.; Basmadjian, G.; Burow, R.; Allen, E.W. (Oklahoma Univ. and Dept. of Veterans Affairs Medical Centre, Oklahoma City, OK (United States))

    1993-10-01

    Mild hydrochloric acid was introduced to a caudal lung section in each of eight dogs to induce injury. Transits of [sup 99m]Tc-labeled red blood cells (RBC) and [[sup 123]I]iodoantipyrine (IAP) injected intravenously were recorded by a scintillation camera. Lungs and blood samples were analyzed post-mortem. Peak-to-equilibrium ratios (P/E) of RBC time-activity curves were computed to be 3.83 [+-] 0.54 for the control lung, 2.58 [+-] 0.55 for the injured lung and 2.23 [+-] 0.58 for the injured caudal section. For IAP, the respective results were 3.78 [+-] 0.29, 2.02 [+-] 0.18 and 1.77 [+-] 0.17. The decrease of P/E in injured areas was attributed to reduced blood flow. Using mean transit times of the tracers, we computed extravascular lung water per unit blood volume to be 0.35 [+-] 0.18 for the control lungs and an increased value of 0.68 [+-] 0.24 for the injured lungs. These results displayed sensitivity to injury, but were gross underestimates relative to the corresponding values of 2.04 [+-] 0.54 and 4.56 [+-] 1.85 in post-mortem analyses. (Author).

  5. PREOPERATIVE PREDICTION OF LUNG FUNCTION IN PNEUMONECTOMY BY SPIROMETRY AND LUNG PERFUSION SCINTIGRAPHY

    Science.gov (United States)

    Cukic, Vesna

    2012-01-01

    Introduction: Nowadays an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused by common etiologic factor - smoking cigarettes. Loss of lung tissue in such patients can worsen much the postoperative pulmonary function. So it is necessary to asses the postoperative pulmonary function especially after maximal resection, i.e. pneumonectomy. Objective: To check over the accuracy of preoperative prognosis of postoperative lung function after pneumonectomy using spirometry and lung perfusion scinigraphy. Material and methods: The study was done on 17 patients operated at the Clinic for thoracic surgery, who were treated previously at the Clinic for Pulmonary Diseases “Podhrastovi” in the period from 01. 12. 2008. to 01. 06. 2011. Postoperative pulmonary function expressed as ppoFEV1 (predicted postoperative forced expiratory volume in one second) was prognosticated preoperatively using spirometry, i.e.. simple calculation according to the number of the pulmonary segments to be removed and perfusion lung scintigraphy. Results: There is no significant deviation of postoperative achieved values of FEV1 from predicted ones obtained by both methods, and there is no significant differences between predicted values (ppoFEV1) obtained by spirometry and perfusion scintigraphy. Conclusion: It is necessary to asses the postoperative pulmonary function before lung resection to avoid postoperative respiratory failure and other cardiopulmonary complications. It is absolutely necessary for pneumonectomy, i.e.. maximal pulmonary resection. It can be done with great possibility using spirometry or perfusion lung scintigraphy. PMID:23378687

  6. Dihydro-Resveratrol Ameliorates Lung Injury in Rats with Cerulein-Induced Acute Pancreatitis.

    Science.gov (United States)

    Lin, Ze-Si; Ku, Chuen Fai; Guan, Yi-Fu; Xiao, Hai-Tao; Shi, Xiao-Ke; Wang, Hong-Qi; Bian, Zhao-Xiang; Tsang, Siu Wai; Zhang, Hong-Jie

    2016-04-01

    Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans-resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-κB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro-inflammatory response, which was associated with a suppression of the NF-κB signaling pathway.

  7. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette

  8. Protective effect of ghrelin against paraquatinduced acute lung injury in mice

    Institute of Scientific and Technical Information of China (English)

    刘瑶

    2014-01-01

    Objective To measure the levels of ghrelin-induced expression or activation of nuclear factor erythroid 2-re-lated factor 2(Nrf2),heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1)in the PQ-injured lungs of mice and to evaluate the protective effect of ghrelin against paraquat(PQ)-induced acute lung injury in mice.Methods According to the random number table method,50 ICR mice of clean grade were

  9. Partial ventilatory support modalities in acute lung injury and acute respiratory distress syndrome-a systematic review.

    Directory of Open Access Journals (Sweden)

    Sarah M McMullen

    Full Text Available PURPOSE: The efficacy of partial ventilatory support modes that allow spontaneous breathing in patients with acute lung injury (ALI and acute respiratory distress syndrome (ARDS is unclear. The objective of this scoping review was to assess the effects of partial ventilatory support on mortality, duration of mechanical ventilation, and both hospital and intensive care unit (ICU lengths of stay (LOS for patients with ALI and ARDS; the secondary objective was to describe physiologic effects on hemodynamics, respiratory system and other organ function. METHODS: MEDLINE (1966-2009, Cochrane, and EmBase (1980-2009 databases were searched using common ventilator modes as keywords and reference lists from retrieved manuscripts hand searched for additional studies. Two researchers independently reviewed and graded the studies using a modified Oxford Centre for Evidence-Based Medicine grading system. Studies in adult ALI/ARDS patients were included for primary objectives and pre-clinical studies for supporting evidence. RESULTS: Two randomized controlled trials (RCTs were identified, in addition to six prospective cohort studies, one retrospective cohort study, one case control study, 41 clinical physiologic studies and 28 pre-clinical studies. No study was powered to assess mortality, one RCT showed shorter ICU length of stay, and the other demonstrated more ventilator free days. Beneficial effects of preserved spontaneous breathing were mainly physiological effects demonstrated as improvement of gas exchange, hemodynamics and non-pulmonary organ perfusion and function. CONCLUSIONS: The use of partial ventilatory support modalities is often feasible in patients with ALI/ARDS, and may be associated with short-term physiological benefits without appreciable impact on clinically important outcomes.

  10. Early COPD patients with lung hyperinflation associated with poorer lung function but better bronchodilator responsiveness

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-10-01

    Full Text Available Chunlan Chen,* Wenhua Jian,* Yi Gao, Yanqing Xie, Yan Song, Jinping Zheng State Key Laboratory of Respiratory Disease, China National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation. We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II with/without lung hyperinflation.Methods: Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed. Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation. The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD.Results: The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV. The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21–5.70, P=0.000–0.029, especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages. From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness. Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%–75.3% and specificities (70.3%

  11. Nitrogen Dioxide-Induced Acute Lung Injury in Sheep

    Science.gov (United States)

    1994-01-01

    subsequent to inhalation expo- sure. Non- cardiogenic pulmonary edema is produced by brief exposure and unlike hyperoxia (Newman et al., 1983; Fukushima...macrophage number significantly decreased within the 24-h post-exposure period. Examination of lung tissue 24 after NO2 revealed patchy edema , mild hemorrhage...examination of lung tissue 24 h after NO, revealed patchy edema , mild hemorrhage and polymorphonuclear c, and mononuclear leukocyte infiltration. The NO

  12. Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury

    Science.gov (United States)

    Togbe, Dieudonnée; Schnyder-Candrian, Silvia; Schnyder, Bruno; Doz, Emilie; Noulin, Nicolas; Janot, Laure; Secher, Thomas; Gasse, Pamela; Lima, Carla; Coelho, Fernando Rodrigues; Vasseur, Virginie; Erard, François; Ryffel, Bernhard; Couillin, Isabelle; Moser, Rene

    2007-01-01

    Recent studies on endotoxin/lipopolysaccharide (LPS)-induced acute inflammatory response in the lung are reviewed. The acute airway inflammatory response to inhaled endotoxin is mediated through Toll-like receptor 4 (TLR4) and CD14 signalling as mice deficient for TLR4 or CD14 are unresponsive to endotoxin. Acute bronchoconstriction, tumour necrosis factor (TNF), interleukin (IL)-12 and keratinocyte-derived chemokine (KC) production, protein leak and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecules myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adaptor protein (TIRAP), but independent of TIR-domain-containing adaptor-inducing interferon-beta (TRIF). In particular, LPS-induced TNF is required for bronchoconstriction, but dispensable for inflammatory cell recruitment. Lipopolysaccharide induces activation of the p38 mitogen-activated protein kinase (MAPK). Inhibition of pulmonary MAPK activity abrogates LPS-induced TNF production, bronchoconstriction, neutrophil recruitment into the lungs and broncho-alveolar space. In conclusion, TLR4-mediated, bronchoconstriction and acute inflammatory lung pathology to inhaled endotoxin are dependent on TLR4/CD14/MD2 expression using the adapter proteins TIRAP and MyD88, while TRIF, IL-1R1 or IL-18R signalling pathways are dispensable. Further downstream in this axis of signalling, TNF blockade reduces only acute bronchoconstriction, while MAPK inhibition abrogates completely endotoxin-induced inflammation. PMID:18039275

  13. Obesity Is Associated with Neutrophil Dysfunction and Attenuation of Murine Acute Lung Injury

    OpenAIRE

    Kordonowy, Lauren L.; Burg, Elianne; Lenox, Christopher C.; Gauthier, Lauren M.; Petty, Joseph M.; Antkowiak, Maryellen; Palvinskaya, Tatsiana; Ubags, Niki; Rincón, Mercedes; Dixon, Anne E.; Vernooy, Juanita H. J.; Fessler, Michael B.; Poynter, Matthew E.; Suratt, Benjamin T.

    2012-01-01

    Although obesity is implicated in numerous health complications leading to increased mortality, the relationship between obesity and outcomes for critically ill patients appears paradoxical. Recent studies have reported better outcomes and lower levels of inflammatory cytokines in obese patients with acute lung injury (ALI)/acute respiratory distress syndrome, suggesting that obesity may ameliorate the effects of this disease. We investigated the effects of obesity in leptin-resistant db/db o...

  14. Longitudinal Decline in Lung Function Measurements among Saskatchewan Grain Workers

    Directory of Open Access Journals (Sweden)

    Punam Pahwa

    2003-01-01

    Full Text Available OBJECTIVE: To evaluate the relationship between the long term effects of grain dust and decline in lung function among grain elevator workers in Saskatchewan, studied over a 15-year period.

  15. Acute effects of inhaled urban particles and ozone: lung morphology, macrophage activity, and plasma endothelin-1.

    Science.gov (United States)

    Bouthillier, L; Vincent, R; Goegan, P; Adamson, I Y; Bjarnason, S; Stewart, M; Guénette, J; Potvin, M; Kumarathasan, P

    1998-12-01

    We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air

  16. Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.

    Science.gov (United States)

    Yang, Weimin; Qiang, Dongjin; Zhang, Min; Ma, Limei; Zhang, Yonghui; Qing, Chen; Xu, Yunlong; Zhen, Chunlan; Liu, Jikai; Chen, Yan-Hua

    2011-06-01

    Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isoforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200 μM) and dexamethasone (65 μM, positive control) inhibited lipopolysaccharide (10 mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-α levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5mg/kg, i.v., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 μM) and dexamethasone (10 μM) pre-incubation lowered lipopolysaccharide (2 μg/mL) induced secretion of the cytokine TNF-α, and interleukins (IL)-1β, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of inflammatory responses and proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8.

  17. Hyperinsulinemia adversely affects lung structure and function

    DEFF Research Database (Denmark)

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K

    2016-01-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that in...

  18. Hyperinsulinemia Adversely Affects Lung Structure and Function

    NARCIS (Netherlands)

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen Kumar; Pattnaik, Bijay; Gheware, Atish; Kolumam Parameswaran, Praveen; Thompson, Michael A; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina M; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-01-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance and epidemiological associations with asthma, this is a critical lacuna; more so with inhaled insulin on the horizon. Here, we demonstrate that insuli

  19. Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review

    Science.gov (United States)

    Ribeiro, Luis IG; Ind, Philip W

    2016-01-01

    As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes. PMID:27763599

  20. Respiratory inductive plethysmography accuracy at varying PEEP levels and degrees of acute lung injury

    NARCIS (Netherlands)

    D.G. Markhorst (Dick); M.A. van Van Gestel (Miriam); H.R. van Genderingen (Huibert); J.J. Haitsma (Jack); B.F. Lachmann (Burkhard); A.J. van Vught (Adrianus)

    2006-01-01

    textabstractBackground and objective: This study was performed to assess the accuracy of respiratory inductive plethysmographic (RIP) estimated lung volume changes at varying positive end-expiratory pressures (PEEP) during different degrees of acute respiratory failure. Methods: Measurements of insp

  1. Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury

    OpenAIRE

    Bertorelli,Giuseppina; Pesci, Alberto; Peveri, Silvia; Mergoni, Mario; Corradi, Attilio; Cantoni, Anna Maria; Tincani, Giovanni; Bobbio, Antonio; Rusca, Michele; Carbognani, Paolo

    2008-01-01

    Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury correspondence: Corresponding author. Tel.: +390521703883; fax: +390521703493. (Carbognani, Paolo) (Carbognani, Paolo) Dipartimento di Clinica Medica - Nefrologia e Scienze della Prevenzione--> , University of Parma--> - ITALY (Bertorelli, Giuseppina) Dipartimento di Clinica Medica - Nefrologia e Scienze della...

  2. Hemodynamic effects of partial liquid ventilation with perfluorocarbon in acute lung injury

    NARCIS (Netherlands)

    R.J.M. Houmes (Robert Jan); S.J.C. Verbrugge (Serge); E. Hendrik (Edwin); B.F. Lachmann (Burkhard)

    1995-01-01

    textabstractObjective: To assess the effect of partial liquid ventilation with perfluorocarbons on hemodynamics and gas exchange in large pigs with induced acute lung injury (ALI). Design: Randomized, prospective, double-control, experimental study. Setting: Experimental intensive care unit of a uni

  3. Acute lung injury in 2003%2003年度急性肺损伤

    Institute of Scientific and Technical Information of China (English)

    Roger G SPRAGG

    2003-01-01

    During the past several decades, clinical investigators world-wide have continued to study the causes,pathophysiology, and treatment strategies for acute lung injury (ALl). This syndrome, which is characterized by nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, is slowly becoming better understood as a result of these efforts.

  4. Non-invasive diagnosis of acute heart- or lung-transplant rejection using radiolabeled annexin V

    Energy Technology Data Exchange (ETDEWEB)

    Blankenberg, F.G. [Stanford Univ., CA (United States). Dept. of Radiology; Strauss, H.W. [Stanford Univ., CA (United States). Nuclear Medicine Div.

    1999-05-01

    Background. Apoptosis is a ubiquitous set of cellular processes by which superfluous or unwanted cells are eliminated in the body without harming adjacent healthy tissues. When apoptosis is inappropriate (too little or too much), a variety of human diseases can occur, including acute heart or lung transplant rejection. Objective. Our group has developed a new radiopharmaceutical, radiolabeled annexin V, which can image apoptosis. Results and conclusion. Here we briefly review the biomolecular basis of apoptosis and its role in acute rejection. We also describe the possible use of radiolabeled annexin V to screen children noninvasively for acute rejection following organ transplantation. (orig.) With 6 figs., 53 refs.

  5. Effect of partial liquid ventilation on lung function in oleic acid-induced lung injury model of piglets

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ji-zhuo; LI Ling-ke; ZHANG Yan-bo; LI Gang; XU Yu-lin; ZHU Yao-bin

    2013-01-01

    Background Pediatric patients are susceptible to lung injury that does not respond to traditional therapies.Partial liquid ventilation (PLV) has been developed as an alternative ventilatory strategy for treating severe lung injury.The aim of this study is to investigate the effect of PLV on lung function in immature piglets.Methods Acute lung injury was induced in 12 Chinese immature piglets by oleic acid (OA).The animals were randomly assigned to two groups (n=6 each group):(1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group.Mean arterial blood pressure (MAP),mean pulmonary arterial pressure (MPAP),central venous pressure (CVP),left atrial pressure (LAP),systemic vascular resistance (SVR),pulmonary vascular resistance (PVR),cardiac output (CO),mean pressure of airway (Paw),dynamic lung compliance (Cydn),and arterial blood gases were measured during the observation period.Results No piglet died in either group with severe lung injury.After four hours of ventilation,pH in the MV group gradually decreased to lower than 7.20,while in the PLV group,pH also gradually decreased but remained higher than 7.20 (P <0.05).Partial pressure of oxygen in artery (PaO2) decreased in both groups,but with a significant difference between the PLV group and MV group (P <0.05).Partial pressure of carbon dioxide in artery (PaCO2) increased in both groups,but with a significant difference between the PLV group and MV group (P <0.05).Paw increased in both groups,but was not significantly different (P >0.05).Cydn decreased in both groups,but without a significant difference (P >0.05).At four hours,heart rate (HR) and MAP in both groups decreased.MPAP in both groups increased,and there was a significant difference between the two groups (P <0.05).CVP was stable in both groups.At four hours,PVR and LAP were increased in both groups.CO was decreased in both groups (P <0.05).SVR was stable during the observation time.Conclusion PLV did not

  6. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS.

    Science.gov (United States)

    Sepehr, Reyhaneh; Audi, Said H; Maleki, Sepideh; Staniszewski, Kevin; Eis, Annie L; Konduri, Girija G; Ranji, Mahsa

    2013-07-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  7. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    NARCIS (Netherlands)

    A. de Lang (Anna); T. Baas (Tracey); T.H. Teal (Thomas); L.M.E. Leijten (Lonneke); B. Rain (Brandon); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); M.G. Katze (Michael)

    2007-01-01

    textabstractThe pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs o

  8. Protective Effect of Genistein on Lipopolysaccharide-induced Acute Lung Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    LI Xingwang; XU Tao; LIAN Qingquan; ZENG Bangxiong; ZHANG Bing; XIE Yubo

    2005-01-01

    To investigate the protective effect of genistein on endotoxin-induced acute lung injury in rats, and explore the underlying mechanisms, 32 male Sprague-Dawley rats were randomly divided into 4 experimental groups: saline control, genistein alone, lipopolysaccaride alone, and genistein pretreatment. Each treatment group consisted of eight animals. Animals were observed for 6 h after LPS challenge, and the wet/dry (W/D) weight ratio of the lung and bronchoalveolar lavage fluid(BALF) protein content were used as a measure of lung injury. Neutrophil recruitment and activation were evaluated by BALF cellularity and myeloperoxidase (MPO) activity. RT-PCR analysis was performed in lung tissue to assess gene expression of ICAM-1. The histopathological changes were also observed using the HE staining of lung tissue. Our results showed that lung injury parameters, including the wet/dry weight ratio and protein content in BALF, were significantly higher in the LPS alone group than in the saline control group (P<0.01). In the LPS alone group, a larger number of neutrophils and greater MPO activity in cell-free BAL and lung homogenates were observed when compared with the saline control group (P<0.01). There was a significant increase in lung ICAM-1 mRNA in response to LPS challenge (P< 0. 01, group L versus group S).Genistein pretreatment significantly attenuated LPS-induced changes in these indices. LPS caused extensive lung damage, which was also lessened after genistein pretreatment. All above-mentioned parameters in the genistein alone group were not significantly different from those of the saline control group. It is concluded that genistein pretreatment attenuated LPS-induced lung injury in rats.This beneficial effect of genistein may involves, in part, an inhibition of neutrophilic recruitment and activity, possibly through an inhibition of lung ICAM-1 expression.

  9. Upregulation of Shh and Ptc1 in hyperoxia‑induced acute lung injury in neonatal rats.

    Science.gov (United States)

    Dang, Hongxing; Wang, Shaohua; Yang, Lin; Fang, Fang; Xu, Feng

    2012-08-01

    The aim of the present study was to observe the expression of sonic hedgehog (Shh) and Ptc signaling molecules in the lungs of newborn rats exposed to prolonged hyperoxia, and to explore the role of the SHH signaling pathway in hyperoxia‑induced lung injury. Newborn Sprague-Dawley rat pups were placed in chambers containing room air or oxygen above 95% for 14 days following birth. The rats were sacrificed after 3, 7 or 14 days and their lungs were removed. Sections were fixed and subjected to hematoxylin and eosin (H&E) staining. Shh and Ptc1 were quantitated by immunohistochemistry. The total RNA and protein were also extracted from lung tissue; real-time PCR (RT-PCR) and western blot analysis were utilized to assess the mRNA and protein expression of Shh and Ptc1. H&E staining demonstrated significant histomorphological changes in the hyperoxia‑exposed lungs at 3, 7 and 14 days of age. The results of the immunohistochemistry, RT-PCR and western blot analysis demonstrated that the expression of Shh was significantly higher in the hyperoxia-exposed lungs at 3, 7 and 14 days, while Ptc1 was significantly elevated at 7 and 14 days. Exposure of the neonatal rat lung to prolonged hyperoxia resulted in acute lung injury and histomorphological changes. Shh and Ptc1 were upregulated in a time-dependent manner in the course of hyperoxia-induced lung injury. The SHH signal pathway may be involved in the pathogenesis of hyperoxia-induced lung injury. This is the first evidence that in vivo hyperoxia induces activation of the SHH signal transduction pathway in newborn lung.

  10. Gallbladder Metastasis of Non-small Cell Lung Cancer Presenting as Acute Cholecystitis

    Institute of Scientific and Technical Information of China (English)

    Yu-Sook Jeong; Seung-Taik Kim; Hye-Suk Han; Sung-Nam Lim; Mi-Jin Kim; Joung-Ho Han; Min-Ho Kang; Dong-Hee Ryu; Ok-Jun Lee; Ki-Hyeong Lee

    2012-01-01

    Although non-small cell lung cancer (NSCLC) can metastasize to almost any organ,metastasis to the gallbladder with significant clinical manifestation is relatively rare.Here,we report a case of gallbladder metastasis of NSCLC presenting as acute cholecystitis.A 79-year-old man presented with pain in the right upper quadrant and fever.A computed tomography (CT) scan of the chest and abdomen showed a cavitary mass in the right lower lobe of the lung and irregular wall thickening of the gallbladder.Open cholecystectomy and needle biopsy of the lung mass were performed.Histological examination of the gallbladder revealed a moderately-differentiated squamous cell carcinoma displaying the same morphology as the lung mass assessed by needle biopsy.Subsequent immunohistochemical examination of the gallbladder and lung tissue showed that the tumor cells were positive for P63 but negative for cytokeratin 7,cytokeratin 20 and thyroid transcription factor-1.A second primary tumor of the gallbladder was excluded by immunohistochemical methods,and the final pathological diagnosis was gallbladder metastasis of NSCLC.Although the incidence is extremely rare,acute cholecystitis can occur in association with lung cancer metastasis to the gallbladder.

  11. Influence of low molecular heparin on blood coagulation function and lung function in AECOPD patients

    Institute of Scientific and Technical Information of China (English)

    Rui Deng

    2016-01-01

    Objective:To explore the influence of low molecular heparin on the blood coagulation function and lung function in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Methods:A total of 100 cases AECOPD patients were divided into observation group and control group according to the present order and odd number by half. They were all given AECOPD conventional symptomatic treatment, on this basis, patients in the observation group were treated with low molecular heparin, 10 d after treatment, arterial blood gas index such as oxygen partial pressure (PaO2), oxygen saturation (SaO2), carbon dioxide partial pressure (PaCO2), pulmonary function index such as forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), FEV1/FVC, blood coagulation function index such as fibrinogen (Fib), D-dimer (D-D), activated partial blood coagulation time (APTT) live enzymes, plasma prothrombin time (PT), thrombin time (TT) between two groups before and after treatment were compared.Results:Compared with before treatment, the levels of PaO2, SaO2, FEV1 and FVC, FEV1/FVC in control group after treatment were significantly elevated, PaCO2, D-D were significantly reduced, the difference were statistically significant (P<0.05); The levels of PaO2, SaO2, FEV1 and FVC, FEV1/FVC, PT, TT and APTT in observation group after treatment were significantly increased, and were significantly higher than the control group after treatment, PaCO2, D-D, Fib were significantly lower, and were lower than the control group after treatment, the differences were statistically significant (allP<0.05).Conclusions:AECOPD patients treated with low molecular heparin can help to improve the arterial blood gas, lung function and blood coagulation function.

  12. COPD 急性加重期和稳定期患者的肺功能评估及其与血清促炎因子、趋化因子的相关性%Lung function in patients with acute exacerbation and stable COPD and its correlation with serum proinflammatory cytokines and chemokines

    Institute of Scientific and Technical Information of China (English)

    王新杰

    2016-01-01

    目的::分析慢性阻塞性肺疾病(COPD)急性加重期和稳定期患者的肺功能评估及其与血清促炎因子、趋化因子的相关性.方法:87例 COPD 患者根据病情分为处于急性加重期的观察组患者32例、处于稳定期的对照组患者55例.对比两组患者的肺功能指标,血清促炎因子、趋化因子含量差异,进一步分析肺功能指标与血清促炎因子、趋化因子含量的相关关系.结果:观察组患者的 FEV1、FVC、FEV1/FVC、FEF75、PEF、IC 水平均显著低于对照组患者;血清促炎因子 IL-1β、IL-4、IL-18、IL-23、TNF-α、IFN-γ含量显著高于对照组患者;血清趋化因子 Eotaxin、MDC、FKN、MCP-1、CCL18、RAN-TES 含量均显著高于对照组患者.COPD 患者的 FEV1、FVC、FEV1/FVC 水平与促炎因子、趋化因子含量呈负相关关系.结论:COPD 急性加重期肺功能下降,促炎因子及趋化因子的含量变化均参与其中.%Objective:To analyze the lung function in patients with acute exacerbation and stable COPD and its correla-tion with serum proinflammatory factors and chemokines.Methods:A total of 87 patients with chronic obstructive pulmonary disease (COPD)were divided into observation group (n =32)at acute exacerbation phase and control group (n =55)at stable phase according to the illness.Differences in lung function indexes and serum levels of proinflammatory cytokines,chemokines were compared between two groups of patients,and the correlation between lung function indexes and serum levels of proin-flammatory cytokines and chemokines was further analyzed.Results:FEV1,FVC,FEV1/FVC,FEF75,PEF and IC levels of observation group were significantly lower than those of control group;serum proinflammatory cytokines IL-1β,IL-4,IL-18, IL-23,TNF-αand IFN-γ content were significantly higher than those of control group;serum chemokines Eotaxin,MDC, FKN,MCP-1,CCL18 and RANTES content were significantly higher than those of control

  13. Lung morphometry: the link between structure and function.

    Science.gov (United States)

    Weibel, Ewald R

    2017-03-01

    The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.

  14. Toll-Like Receptor-9 (TLR9) is Requisite for Acute Inflammatory Response and Injury Following Lung Contusion.

    Science.gov (United States)

    Suresh, Madathilparambil V; Thomas, Bivin; Dolgachev, Vladislav A; Sherman, Matthew A; Goldberg, Rebecca; Johnson, Mark; Chowdhury, Aulina; Machado-Aranda, David; Raghavendran, Krishnan

    2016-10-01

    Lung contusion (LC) is a significant risk factor for the development of acute respiratory distress syndrome. Toll-like receptor 9 (TLR9) recognizes specific unmethylated CpG motifs, which are prevalent in microbial but not vertebrate genomic DNA, leading to innate and acquired immune responses. TLR9 signaling has recently been implicated as a critical component of the inflammatory response following lung injury. The aim of the present study was to evaluate the contribution of TLR9 signaling to the acute physiologic changes following LC. Nonlethal unilateral closed-chest LC was induced in TLR9 (-/-) and wild-type (WT) mice. The mice were sacrificed at 5, 24, 48, and 72-h time points. The extent of injury was assessed by measuring bronchoalveolar lavage, cells (cytospin), albumin (permeability injury), and cytokines (inflammation). Following LC, only the TLR9 (-/-) mice showed significant reductions in the levels of albumin; release of pro-inflammatory cytokines IL-1β, IL-6, and Keratinocyte chemoattractant; production of macrophage chemoattractant protein 5; and recruitment of alveolar macrophages and neutrophil infiltration. Histological evaluation demonstrated significantly worse injury at all-time points for WT mice. Macrophages, isolated from TLR9 (-/-) mice, exhibited increased phagocytic activity at 24 h after LC compared with those isolated from WT mice. TLR9, therefore, appears to be functionally important in the development of progressive lung injury and inflammation following LC. Our findings provide a new framework for understanding the pathogenesis of lung injury and suggest blockade of TLR9 as a new therapeutic strategy for the treatment of LC-induced lung injury.

  15. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen.

    Directory of Open Access Journals (Sweden)

    Andrew S Brown

    2016-06-01

    Full Text Available Legionella pneumophila is the causative agent of Legionnaires' disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC, which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

  16. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen.

    Science.gov (United States)

    Brown, Andrew S; Yang, Chao; Fung, Ka Yee; Bachem, Annabell; Bourges, Dorothée; Bedoui, Sammy; Hartland, Elizabeth L; van Driel, Ian R

    2016-06-01

    Legionella pneumophila is the causative agent of Legionnaires' disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC), which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

  17. Radiation induces acute alterations in neuronal function.

    Directory of Open Access Journals (Sweden)

    Peter H Wu

    Full Text Available Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(ARs. These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

  18. Inhaled Nitric Oxide for Acute Respiratory Distress Syndrome and Acute Lung Injury in Adults and Children: A Systematic Review with Meta-Analysis and Trial Sequential Analysis

    DEFF Research Database (Denmark)

    Afshari, Arash; Brok, Jesper; Møller, Ann

    2011-01-01

    BACKGROUND: Acute hypoxemic respiratory failure, defined as acute lung injury and acute respiratory distress syndrome, are critical conditions associated with frequent mortality and morbidity in all ages. Inhaled nitric oxide (iNO) has been used to improve oxygenation, but its role remains...... be recommended for patients with acute hypoxemic respiratory failure. iNO results in a transient improvement in oxygenation but does not reduce mortality and may be harmful....

  19. Protective Effect of Rhubarb on Endotoxin-Induced Acute Lung Injury

    Institute of Scientific and Technical Information of China (English)

    李春盛; 周景; 桂培春; 何新华

    2001-01-01

    To approach the mechanism of lipopolysaccharide (LPS) in causing acute lung injury (ALI) and the protective effect of rhubarb and dexamethasone, lung specimens were examined with macroscopy, microscopy, electron microscopy and the biological markers of ALI including lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary capillary permeability and pulmonary alveolar permeability index were observed. The mechanism of the ALI is mainly due to direct injury of alveolar epithelium and pulmonary vascular endothelium. Rhubarb and dexamethasone could significantly reduce the edema of the lung tissue, decrease the red blood cell exudation, neutrophil infiltration and plasma protein exudation in the alveoli and all the biological markers in comparison with the ALI model rats, indicating they have protective action on vascular endothelium and alveolar epithelium.

  20. Lung Transplantation in Acute Respiratory Distress Syndrome Caused by Influenza Pneumonia

    Directory of Open Access Journals (Sweden)

    Youjin Chang

    2015-08-01

    Full Text Available Severe acute respiratory distress syndrome (ARDS is a life-threatening disease with a high mortality rate. Although many therapeutic trials have been performed for improving the mortality of severe ARDS, limited strategies have demonstrated better outcomes. Recently, advanced rescue therapies such as extracorporeal membrane oxygenation (ECMO made it possible to consider lung transplantation (LTPL in patients with ARDS, but data is insufficient. We report a 62-year-old man who underwent LTPL due to ARDS with no underlying lung disease. He was admitted to the hospital due to influenza A pneumonia-induced ARDS. Although he was supported by ECMO, he progressively deteriorated. We judged that his lungs were irreversibly damaged and decided he needed to undergo LTPL. Finally, bilateral sequential double-lung transplantation was successfully performed. He has since been alive for three years. Conclusively, we demonstrate that LTPL can be a therapeutic option in patients with severe ARDS refractory to conventional therapies.

  1. Piperine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Modulating NF-κB Signaling Pathways.

    Science.gov (United States)

    Lu, Ying; Liu, Jingyao; Li, Hongyan; Gu, Lina

    2016-02-01

    Piperine, one of the active components of black pepper, has been reported to have antioxidant and anti-inflammatory activities. However, the effects of piperine on lipolysaccharide (LPS)-induced acute lung injury (ALI) have not been reported. Thus, the protective effects of piperine against LPS-induced ALI were investigated in this study. LPS-induced lung injury was assessed by histological study, myeloperoxidase (MPO) activity, and inflammatory cytokine production. Our results demonstrated that piperine attenuated LPS-induced MPO activity, lung edema, and inflammatory cytokines TNF-α, IL-6, and IL-1β production. Histological studies showed that piperine obviously attenuated LPS-induced lung injury. In addition, piperine significantly inhibited LPS-induced NF-κB activation. In conclusion, our results demonstrated that piperine had a protective effect on LPS-induced ALI. The anti-inflammatory mechanism of piperine is through inhibition of NF-κB activation. Piperine may be a potential therapeutic agent for ALI.

  2. Therapeutic experience of the application of anisodamine on acute lung injury

    Institute of Scientific and Technical Information of China (English)

    Nan-Bin Yu

    2016-01-01

    /L], IL-8 [(93.68 ± 12.52) vs. (145.62 ± 22.65) ng/L], IL-10 [(205.64 ± 31.56) vs. (336.62 ± 51.38) ng/L] and myeloid cells-1 (73.32 ± 10.39 vs. 114.45 ± 18.51) of patients in experimental group were significantly lower than those in the control group. Conclusions: The anisodamine combining with conventional therapy can relieve the degree of lung injury caused by acute pulmonary contusion, improve ventilatory function, lower the incidence of acute respiratory distress syndrome and multiple organ dysfunction syndrome and inhibit the activation of inflammatory reaction and the release of inflam-matory mediators.

  3. Therapeutic exper ience of the application of anisodamine on acute lung injur y

    Directory of Open Access Journals (Sweden)

    Nan-Bin Yu

    2016-09-01

    .54 ng/L], IL-8 [(93.68 ± 12.52 vs. (145.62 ± 22.65 ng/L], IL-10 [(205.64 ± 31.56 vs. (336.62 ± 51.38 ng/L] and myeloid cells-1 (73.32 ± 10.39 vs. 114.45 ± 18.51 of patients in experimental group were significantly lower than those in the control group. Conclusions: The anisodamine combining with conventional therapy can relieve the degree of lung injury caused by acute pulmonary contusion, improve ventilatory function, lower the incidence of acute respiratory distress syndrome and multiple organ dysfunction syndrome and inhibit the activation of inflammatory reaction and the release of inflammatory mediators.

  4. Lung function is associated with arterial stiffness in children.

    Directory of Open Access Journals (Sweden)

    Julian G Ayer

    Full Text Available BACKGROUND: In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life. OBJECTIVE: To determine the relationship between lung function and carotid augmentation index (AIx, a measure of vascular stiffness, in 8-year old children. METHODS: Data on brachial blood pressure, lung function (FEV(1, FVC, FEV(1/FVC, obtained by spirometry and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention as covariates. RESULTS: In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = -0.17,b = -6.72, partial R(2 = .02, p = 0.03, FVC (standardised β = -0.29, b = -9.31, partial R(2 = 0.04, p<0.001 and FEV1/FVC (standardised β = .13, b = 18.4, partial R(2 = 0.02, p = 0.04. CONCLUSION: Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems.

  5. Leukotriene biosynthesis inhibition ameliorates acute lung injury following hemorrhagic shock in rats

    Directory of Open Access Journals (Sweden)

    Hadi Najah R

    2011-06-01

    Full Text Available Abstract Background Hemorrhagic shock followed by resuscitation is conceived as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. MK-886 is a leukotriene biosynthesis inhibitor exerts an anti inflammatory and antioxidant activity. Objectives The objective of present study was to assess the possible protective effect of MK-886 against hemorrhagic shock-induced acute lung injury via interfering with inflammatory and oxidative pathways. Materials and methods Eighteen adult Albino rats were assigned to three groups each containing six rats: group I, sham group, rats underwent all surgical instrumentation but neither hemorrhagic shock nor resuscitation was done; group II, Rats underwent hemorrhagic shock (HS for 1 hr then resuscitated with Ringer's lactate (1 hr (induced untreated group, HS; group III, HS + MK-886 (0.6 mg/kg i.p. injection 30 min before the induction of HS, and the same dose was repeated just before reperfusion period. At the end of experiment (2 hr after completion of resuscitation, blood samples were collected for measurement of serum tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6. The trachea was then isolated and bronchoalveolar lavage fluid (BALF was carried out for measurement of leukotriene B4 (LTB4, leukotriene C4 (LTC4 and total protein. The lungs were harvested, excised and the left lung was homogenized for measurement of malondialdehyde (MDA and reduced glutathione (GSH and the right lung was fixed in 10% formalin for histological examination. Results MK-886 treatment significantly reduced the total lung injury score compared with the HS group (P 4, LTC4 & total protein compared with the HS group (P P Conclusions The results of the present study reveal that MK-886 may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating the role of

  6. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response...... that in chemokine-dependent inflammatory responses in lung CC chemokines do not necessarily demonstrate redundant function.......The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES...

  7. Correlative relationship among oxidative stress and lung function, maximal respiratory muscle strength in patients with COPD in acute exacerbation period%AECOPD氧化应激与肺功能、最大呼吸肌力动态变化相关性研究

    Institute of Scientific and Technical Information of China (English)

    邓桂胜; 罗勇; 徐卫国; 揭志军; 王莹

    2012-01-01

    Objective To study the correlative relationship among oxidative stress and lung function, maximal respiratory muscle strength in patients with COPD in acute exacerbation period. Methods Serum concentrations of malondialdehyde (MDA), glutathione ( GSH), glutathione disulfide (GSSG), superoxide dismutase (SOD) were detected in 47 patients with COPD in acute exacerbation period through ELISA, which were correlatively analyzed to yearly-decreased value of forced expiratory volume in one second ( △FEV1) , forced vital capacity ( △FVC), and maximal inspiratory pressure ( △MIP). Results There were a positive correlative relationship between MDA and △FEV1, a negatively correlated relationship between GSH,GSH/GSSG and △FEV1 respectively, a negatively correlated relationship between GSH and A MIP. There was no other significant relationships reported. Conclusion Oxidants/antioxidants imbalance deteriorates lung function and maximal respiratory muscle strength in patients with COPD in acute exacerbation period.%目的 研究AECOPD患者氧化应激与肺功能、最大呼吸肌力动态变化的相关性.方法ELISA检测47例COPD急性加重期患者血清丙二醛(MDA)、谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)、超氧化物歧化酶(SOD)浓度,与其第一秒钟用力呼气容积( FEV1)、用力肺活量(FVC)、最大吸气压(MIP)年下降值进行相关性分析.结果 MDA与FEV1年下降值呈正相关,GSH、GSH/GSSG与FEV1年下降值呈负相关,GSH与MIP年下降值呈负相关.结论 COPD急性加重期氧化/抗氧化失衡加速COPD的肺功能下降和呼吸肌力的减弱.

  8. Amiodarone-induced acute lung toxicity in an ICU setting.

    Science.gov (United States)

    Skroubis, G; Skroubis, T; Galiatsou, E; Metafratzi, Z; Karahaliou, A; Kitsakos, A; Nakos, G

    2005-04-01

    Amiodarone is a highly effective antiarrhythmic drug, albeit notorious for its serious pulmonary toxicity. The incidence of amiodarone-induced pulmonary toxicity (APT) appears to be 1% per year (1). We report a case of very acute APT in a man suffering from postoperative atrial fibrillation.

  9. A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Rector Edward S

    2004-11-01

    Full Text Available Abstract Background Biologically variable ventilation (return of physiological variability in rate and tidal volume using a computer-controller was compared to control mode ventilation with and without a recruitment manoeuvre – 40 cm H2O for 40 sec performed hourly; in a porcine oleic acid acute lung injury model. Methods We compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (FIO2 = 0.3; PEEP 5 cm H2O in control mode until PaO2 decreased to 60 mm Hg with oleic acid infusion (PaO2/FIO2 2O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury. Results PaO2 and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry. Conclusions In this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.

  10. [Thyroid function tests in acute drug intoxication].

    Science.gov (United States)

    Tseng, F Y; Chen, C S

    1992-03-01

    It is well known that thyroid function tests may be changed in non-thyroidal illnesses. To understand the influence of acute drug intoxication on thyroid function tests, 31 drug intoxicated patients without previous thyroid disorders and systemic diseases were included in our study. T3, T4, TSH, and resin T3 uptake were checked as soon as they arrived at our emergency service and were compared to that of 58 healthy volunteers. Within 31 patients, 14 were intoxicated by organophosphorous compounds, 6 by sedatives and hypnotics, 3 by strong acid, 2 by paraquet, 2 by rodenticides (warfarin), 2 by lysol and the other 2 were intoxicated by acetaminophen. The mean T3 and TSH levels were significantly lower in the drug intoxicated group. Among the 31 patients, 14 (45.2%) had a low T3, 2 (6.5%) had a low T3 and T4, and 6 (19.3%) had an elevated T4. All of the patients with an elevated T4 were intoxicated by organophosphates. If we divided the 31 patients into 2 subgroups: organophosphate intoxicated group and non-organophosphate intoxicated group, T4 and FT4I were significantly higher in the former group. Thyroid function tests became normal after treatment in 27 patients, discharged in good general condition. T3 and T4 became extremely low in 4 patients before they expired. The present study confirms that acute drug intoxication, like other non-thyroidal illnesses, affects thyroid function tests. Acute organophosphate intoxication may cause transient hyperthyroxinemia.

  11. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr [Seoul National University Hospital, Biomedical Research Institute and Institute of Forensic Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Abdelmegeed, Mohamed A. [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States); Song, Byoung-Joon, E-mail: bj.song@nih.gov [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)

    2013-07-05

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.

  12. A model of hemorrhagic shock and acute lung injury in Landrace-Large White Swine.

    Science.gov (United States)

    Xanthos, Theodoros T; Balkamou, Xanthippi A; Stroumpoulis, Kostantinos I; Pantazopoulos, Ioannis N; Rokas, Georgios I; Agrogiannis, Georgios D; Troupis, Georgios T; Demestiha, Theano D; Skandalakis, Panagiotis N

    2011-04-01

    Traumatic injury is a leading cause of death worldwide for people between 5 and 44 y of age, and it accounts for 10% of all deaths. The incidence of acute lung injury, a life-threatening complication in severely injured trauma patients remains between 30% and 50%. This study describes an experimental protocol of volume-controlled hemorrhage in Landrace-Large White swine. The experimental approach simulated the clinical situation associated with hemorrhagic shock in the trauma patient while providing controlled conditions to maximize reproducibility. The duration of the protocol was 8 h and was divided into 5 distinct phases-stabilization, hemorrhage, maintenance, resuscitation, and observation-after which the swine were euthanized. Lung tissue samples were analyzed histologically. All swine survived the protocol. The hemodynamic responses accurately reflected those seen in humans, and the development of acute lung injury was consistent among all swine. This experimental protocol of hemorrhagic shock and fluid resuscitation in Landrace-Large White swine may be useful for future study of hemorrhagic shock and acute lung injury.

  13. A Model of Hemorrhagic Shock and Acute Lung Injury in Landrace–Large White Swine

    Science.gov (United States)

    Xanthos, Theodoros T; Balkamou, Xanthippi A; Stroumpoulis, Kostantinos I; Pantazopoulos, Ioannis N; Rokas, Georgios I; Agrogiannis, Georgios D; Troupis, Georgios T; Demestiha, Theano D; Skandalakis, Panagiotis N

    2011-01-01

    Traumatic injury is a leading cause of death worldwide for people between 5 and 44 y of age, and it accounts for 10% of all deaths. The incidence of acute lung injury, a life-threatening complication in severely injured trauma patients remains between 30% and 50%. This study describes an experimental protocol of volume-controlled hemorrhage in Landrace–Large White swine. The experimental approach simulated the clinical situation associated with hemorrhagic shock in the trauma patient while providing controlled conditions to maximize reproducibility. The duration of the protocol was 8 h and was divided into 5 distinct phases—stabilization, hemorrhage, maintenance, resuscitation, and observation—after which the swine were euthanized. Lung tissue samples were analyzed histologically. All swine survived the protocol. The hemodynamic responses accurately reflected those seen in humans, and the development of acute lung injury was consistent among all swine. This experimental protocol of hemorrhagic shock and fluid resuscitation in Landrace–Large White swine may be useful for future study of hemorrhagic shock and acute lung injury. PMID:21535927

  14. Scintigraphy at 3 months after single lung transplantation and observations of primary graft dysfunction and lung function

    DEFF Research Database (Denmark)

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F;

    2012-01-01

    procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found......, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy...... no significant correlation between lung function distribution at 3 months and PGD at 72 h. There was also no significant correlation between PGD scores at 72 h and lung function at 6 and 12 months. The same applied to scintigraphic scores for heterogeneity at 3 months compared with lung function at 6 and 12...

  15. FCT (functional computed tomography) evaluation of the lung volumes at different PEEP (positive-end expiratory pressure) ventilation pattern, in mechanical ventilated patients

    Energy Technology Data Exchange (ETDEWEB)

    Papi, M.G.; Di Segni, R.; Mazzetti, G.; Staffa, F. [Dept. of Radiology, S. Giovanni HS, Rome (Italy); Conforto, F.; Calimici, R.; Salvi, A. [Dept. of Anesthesiology, S. Giovanni HS, Rome (Italy); Matteucci, G. [Dept. of Pneumology, S. Giovanni HS, Rome (Italy)

    2007-06-15

    Purpose To evaluate with FCT (functional computed tomography) total lung volume and fractional lung volumes at different PEEP (positive end expiratory pressure) values in acute mechanically ventilated patients. Methods Nine ICU (intensive care unity) patients (1 lung pneumonia, 2 polytrauma, 2 sepsis, 3 brain surgery, 1 pulmonary embolism); mean age 48 {+-} 15 years, 6 male, 3 female; GE 16 MDCT scan was performed with acquisition from apex to diaphragma in seven seca at different PEEP values. Raw CT data were analysed by an advantage workstation to obtain volume density masks and histograms of both lungs and each lung and these density ranges were applied: - 1000 - 950 = hyper-ventilated lung, -900 - 650 well aerated lung, -950 - 500 all aerated lung, -500 + 200 lung tissue. Total and fractional lung volumes, Hounsfield unit (HU) were calculated and compared at different PEEP values (0, 5, 10, 15 cm H{sub 2}O). In four patients lung volumes were compared between the more and the less involved lung at increased PEEP. Statistic analysis: comparison means-medians tests. Results Data calculated at five PEEP showed unexpected decrease of total lung volume and increase of lung density (HU); proportionally no significant improvement of oxigenation. (orig.)

  16. Apios americana Medik Extract Alleviates Lung Inflammation in Influenza Virus H1N1- and Endotoxin-Induced Acute Lung Injury.

    Science.gov (United States)

    Sohn, Sung-Hwa; Lee, Sang-Yeon; Cui, Jun; Jang, Ho Hee; Kang, Tae-Hoon; Kim, Jong-Keun; Kim, In-Kyoung; Lee, Deuk-Ki; Choi, Seulgi; Yoon, Il-Sub; Chung, Ji-Woo; Nam, Jae-Hwan

    2015-12-28

    Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

  17. The impact of intravenous fat emulsion administration in acute lung injury.

    Science.gov (United States)

    Lekka, Marilena E; Liokatis, Stamatis; Nathanail, Christos; Galani, Vasiliki; Nakos, George

    2004-03-01

    The aim of this study was to evaluate the effect of parenteral nutrition containing medium- and long-chain triglycerides on the function of the respiratory system and to investigate mechanisms involved in this process. We studied 13 patients with acute respiratory distress syndrome (ARDS), 8 receiving lipid and 5 placebo, and 6 without ARDS, receiving lipid. Bronchoalveolar lavage (BAL) was performed before and 1 hour after administration of lipid or placebo. In patients with ARDS, lipid administration resulted in deterioration of oxygenation (Pa(O(2))/FI(O(2)): from 129 +/- 37 to 95 +/- 42), compliance of respiratory system (from 39.2 +/- 12 to 33.1 +/- 9.2 ml/cm H(2)O), and pulmonary vascular resistance (from 258 +/- 47 to 321 +/- 58 dyne x s x cm(-5)). In the BAL fluid of the same group, an increase in total protein and phospholipid concentrations, phospholipase activities, platelet-activating factor and neutrophils, as well as alterations in BAL lipid profile were observed. No significant changes were observed in the control or in the ARDS-Placebo groups. In conclusion, this study indicates that administration of medium- and long-chain triglycerides in patients with ARDS causes alterations in lung function and hemodynamics. Inflammatory cells, possibly activated by lipids, release phospholipase A(2) and platelet-activating factor, enhancing edema formation, inflammation, and surfactant alterations.

  18. Mechanical ventilation strategies for intensive care unit patients without acute lung injury or acute respiratory distress syndrome: a systematic review and network meta-analysis

    OpenAIRE

    Guo, Lei; Wang, Weiwei; Zhao, Nana; Guo, Libo; Chi, Chunjie; Hou, Wei; Wu, Anqi; Tong, Hongshuang; Wang, Yue; Wang, Changsong; Li, Enyou

    2016-01-01

    Background It has been shown that the application of a lung-protective mechanical ventilation strategy can improve the prognosis of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). However, the optimal mechanical ventilation strategy for intensive care unit (ICU) patients without ALI or ARDS is uncertain. Therefore, we performed a network meta-analysis to identify the optimal mechanical ventilation strategy for these patients. Methods We searched the Cochra...

  19. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

    Full Text Available Abstract Objective Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  20. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

    Full Text Available Objective: Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980-1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries.Method:This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment.Results:Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion:Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  1. Bronchoalveolar lavage alterations during prolonged ventilation of patients without acute lung injury.

    Science.gov (United States)

    Tsangaris, I; Lekka, M E; Kitsiouli, E; Constantopoulos, S; Nakos, G

    2003-03-01

    Mechanical ventilation deteriorates previously injured lung, but little is known about its effect on healthy human lung. This work was designed to assess the effect of prolonged mechanical ventilation on bronchoalveolar lavage (BAL) fluid composition of patients without acute lung injury. Twenty-two ventilated patients (tidal volume 8-10 mL x kg(-1), positive end-expiratory pressure 3-5 cmH2O) without lung injury, who did not develop any complication from the respiratory system during the 2-week study period, were studied. They were subjected to three consecutive BALs, the first during 36 h from intubation, the second at the end of the first week of mechanical ventilation and the third at the end of the second week of mechanical ventilation. Total BAL protein increased during mechanical ventilation (148 +/- 62, 381 +/- 288, 353 +/- 215 microg x mL(-1) BAL for the first, second and third BAL, respectively). In contrast, BAL phospholipids decreased (2.7 +/- 1.1, 1.4 +/- 0.6, 1.2 +/- 0.7 microg x mL(-1) BAL, respectively). Large surfactant aggregates were reduced and inflammatory markers, such as platelet activating factor (PAF), PAF-acetylhydrolase and neutrophils, significantly increased after 1 week, but partially remitted after 2 weeks of mechanical ventilation. In summary, this study demonstrates that prolonged mechanical ventilation even of patients without acute lung injury is associated with the presence of inflammatory markers and surfactant alterations.

  2. Inhaled hydrogen sulfide protects against lipopolysaccharide-induced acute lung injury in mice

    Directory of Open Access Journals (Sweden)

    Faller Simone

    2012-10-01

    Full Text Available Abstract Background Local pulmonary and systemic infections can lead to acute lung injury (ALI. The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury. Methods C57BL/6 N mice received lipopolysaccharide (LPS intranasally in the absence or presence of 80 parts per million H2S. After 6 h, acute lung injury was determined by comparative histology. Bronchoalveolar lavage (BAL fluid was analyzed for total protein content and differential cell counting. BAL and serum were further analyzed for interleukin-1β, macrophage inflammatory protein-2, and/or myeloperoxidase glycoprotein levels by enzyme-linked immunosorbent assays. Differences between groups were analyzed by one way analysis of variance. Results Histological analysis revealed that LPS instillation led to increased alveolar wall thickening, cellular infiltration, and to an elevated ALI score. In the presence of H2S these changes were not observed despite LPS treatment. Moreover, neutrophil influx, and pro-inflammatory cytokine release were enhanced in BAL fluid of LPS-treated mice, but comparable to control levels in H2S treated mice. In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation. Conclusion Inhalation of hydrogen sulfide protects against LPS-induced acute lung injury by attenuating pro-inflammatory responses.

  3. NLRP3 inflammasome activation is essential for paraquat-induced acute lung injury.

    Science.gov (United States)

    Liu, Zhenning; Zhao, Hongyu; Liu, Wei; Li, Tiegang; Wang, Yu; Zhao, Min

    2015-02-01

    The innate immune response is important in paraquat-induced acute lung injury, but the exact pathways involved are not elucidated. The objectives of this study were to determine the specific role of the NLRP3 inflammasome in the process. Acute lung injury was induced by administering paraquat (PQ) intraperitoneally. NLRP3 inflammasome including NLRP3, ASC, and caspase-1 mRNA and protein expression in lung tissue and IL-1β and IL-18 levels in BALF were detected at 4, 8, 24, and 72 h after PQ administration in rats. Moreover, rats were pretreated with 10, 30, and 50 mg/kg NLRP3 inflammasome blocker glybenclamide, respectively, 1 h before PQ exposure. At 72 h after PQ administration, lung histopathology changes, NLRP3, ASC, and caspase-1 protein expression, as well as secretion of cytokines including IL-1β and IL-18 in BALF were investigated. The NLRP3 inflammasome including NLRP3, ASC, caspase-1 expression, and cytokines IL-1β and IL-18 levels in PQ poisoning rats were significantly higher than that in the control group. NLRP3 inflammasome blocker glybenclamide pretreatment attenuated lung edema, inhibited the NLRP3, ASC, and caspase-1 activation, and reduced IL-1β and IL-18 levels in BALF. In the in vitro experiments, IL-1β and IL-18 secreted from RAW264.7 mouse macrophages treated with paraquat were attenuated by glybenclamide. In conclusion, paraquat can induce IL-1β/IL-18 secretion via NLRP3-ASC-caspase-1 pathway, and the NLRP3 inflammasome is essential for paraquat-induced acute lung injury.

  4. IMPACT OF SMOKING ON ADULTS LUNG AGE AND VENTILATORY FUNCTION

    Directory of Open Access Journals (Sweden)

    Omar Farouk Helal

    2014-04-01

    Full Text Available Background: Although a large body of evidence exists on the effect of smoking on lung age and pulmonary function, much less attention has been dedicated to using these effects as an effective strategy in smoking cessation. Objective: The present study was carried out to investigate the impact of smoking on lung age and ventilatory function in adult Saudi in order to use these effects in a future strategy for smoking cessation. Methods: Eighty one smoker students with their mean age 23.88 ± 2.7 years were enrolled in this study. Every student performed a ventilatory function tests in order to measure lung age, forced vital capacity (FVC, forced expiratory volume at the end of the first second (FEV1, FEV1/FVC ratio and peak expiratory flow rate PEFR. Results: The result showed significant deterioration in the mean value of FEV1, PEFR and the estimated lung age and a non-significant difference in the mean values of FVC. Conclusion: Smoking has a significant effect on ventilaroty function and deteriorating estimated lung age.

  5. Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation

    Directory of Open Access Journals (Sweden)

    Priscila Cilene León Bueno de Camargo

    2014-08-01

    Full Text Available Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4. The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients.

  6. [Determination of capillary plasma C-reactive protein during therapy for acute infectious lung diseases].

    Science.gov (United States)

    Makarenko, V V; Vavilikhina, N F; Kastrikina, T N; El'chaninova, S A

    2011-06-01

    Changes in the concentration of C-reactive protein (CRP), leukocytes, erythrocyte sedimentation rate, and differential blood count were comparatively estimated in the treatment of 66 infants (aged 1.12 +/- 0.95 years) with acute infectious lung diseases. There was a high correlation between capillary plasma and venous serum CRP concentrations. On the first day of effective antibiotic therapy, there was a significant decrease in CRP levels; the sensitivity and specificity were 96 and 94%, respectively. Thus, measurement of capillary blood CRP is an accessible and informative tool to monitor therapy for infectious lung diseases in infants.

  7. Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation*

    Science.gov (United States)

    de Camargo, Priscila Cilene León Bueno; Afonso, José Eduardo; Samano, Marcos Naoyuki; Acencio, Milena Marques Pagliarelli; Antonangelo, Leila; Teixeira, Ricardo Henrique de Oliveira Braga

    2014-01-01

    Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4). The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients. PMID:25210966

  8. Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome in Mice

    Science.gov (United States)

    Soeiro-Pereira, Paulo V.; Gomes, Eliane; Neto, Antonio Condino; D' Império Lima, Maria R.; Alvarez, José M.; Portugal, Silvia; Epiphanio, Sabrina

    2016-01-01

    Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS. Mice developing ALI/ARDS showed greater neutrophil accumulation in the lungs compared with mice that did not develop pulmonary complications. In addition, mice with ALI/ARDS produced more neutrophil-attracting chemokines, myeloperoxidase and reactive oxygen species. We also observed that the parasites Plasmodium falciparum and PbA induced the formation of neutrophil extracellular traps (NETs) ex vivo, which were associated with inflammation and tissue injury. The depletion of neutrophils, treatment with AMD3100 (a CXCR4 antagonist), Pulmozyme (human recombinant DNase) or Sivelestat (inhibitor of neutrophil elastase) decreased the development of malaria-associated ALI/ARDS and significantly increased mouse survival. This study implicates neutrophils and NETs in the genesis of experimentally induced malaria-associated ALI/ARDS and proposes a new therapeutic approach to improve the prognosis of severe malaria. PMID:27926944

  9. Determinants of lung function and airway hyperresponsiveness in asthmatic children

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S; Anhøj, J;

    2007-01-01

    Genetic Study (SAGA). RESULTS: The primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N=919). FEV(1) percent predicted (FEV(1)% pred) was 0......BACKGROUND: Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying...... effect of steroid treatment. METHODS: We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma...

  10. Rubberwood dust and lung function among Thai furniture factory workers.

    Science.gov (United States)

    Thetkathuek, Anamai; Yingratanasuk, Tanongsak; Demers, Paul A; Thepaksorn, Phayong; Saowakhontha, Sastri; Keifer, Matthew C

    2010-01-01

    The objective of this study was to assess factors affecting lung function among 685 workers in the rubberwood (Hevea brasiliensis) furniture industry in the Chonburi and Rayung provinces of eastern Thailand. Study data were gathered using questionnaires, by sampling wood dust, and by spirometry. The mean wood dust exposure level in the factories was 4.08 mg/m3 (SD = 1.42, range: 1.15-11.17 mg/m3). The mean overall percent of predicted forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC values were 84 % (SD = 13.41), 86 % (SD = 14.40), and 99% (SD = 10.42), respectively. Significant negative correlations were found between mean dust exposure levels and FVC (p = 0.0008), and FEV1/FVC% (p lung function and wood dust levels among wood workers suggests that rubberwood dust exposure negatively affects lung function.

  11. Sodium butyrate protects against severe burn-induced remote acute lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Xun Liang

    Full Text Available High-mobility group box 1 protein (HMGB1, a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI. Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague-Dawley rats were divided into three groups: 1 sham group, sham burn treatment; 2 burn group, third-degree burns over 30% total body surface area (TBSA with lactated Ringer's solution for resuscitation; 3 burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer's solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D ratio. Tumor necrosis factor (TNF-α and interleukin (IL-8 protein concentrations in bronchoalveolar lavage fluid (BALF and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO activity and malondialdehyde (MDA concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1

  12. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    Science.gov (United States)

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  13. Intercellular Adhension Molecule-1 in the Pathogenesis of Heroin-induced Acute Lung Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    周琼; 白明; 邹世清

    2004-01-01

    The expression of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of heroin-induced acute lung injury (ALI) in rats was investigated. The model of ALI was established by intravenous injection of heroin into tail vein in rats. Thirty-six rats were randomly divided into heroin-treated groups (1 h, 2 h, 4 h, 6 h and 24 h) and normal control group. Changes in histopathologic morphology and biological markers of ALI were measured. The expression of ICAM-1in lung tissue was detected by using immunohistochemistry and RT-PCR. The results showed that the W/D ratio and protein contents in BALF of the heroin-treated groups were significantly higher than that of the control group (P<0.01). The histopathological changes in the lung tissue were more obvious in heroin-treated groups. The ICAM-1 protein and mRNA expression in the lung tissue of heroin-treated groups were significantly increased as compared with that of the control group (P<0.01), and correlated with the ALI parameters in a time-dependent manner. Increasing of ICAM-1 expression was involved in the formation of heroin-induced lung injury. Furthermore, the level of expression was positively correlated with the severity of lung injury.

  14. Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.

    Science.gov (United States)

    Kao, Shang-Jyh; Liu, Demeral David; Su, Chain-Fa; Chen, Hsing I

    2007-09-01

    Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

  15. Leptin attenuates lipopolysaccharide or oleic acid-induced acute lung injury in mice.

    Science.gov (United States)

    Dong, Hai-Ying; Xu, Min; Ji, Zhen-Yu; Wang, Yan-Xia; Dong, Ming-Qing; Liu, Man-Ling; Xu, Dun-Quan; Zhao, Peng-Tao; Liu, Yi; Luo, Ying; Niu, Wen; Zhang, Bo; Ye, Jing; Li, Zhi-Chao

    2013-12-01

    Leptin is reported to be involved in acute lung injury (ALI). However, the role and underlying mechanisms of leptin in ALI remain unclear. The aim of this study was to determine whether leptin deficiency promoted the development of ALI. LPS or oleic acid (OA) were administered to wild-type and leptin deficient (ob/ob) mice to induce ALI. Leptin level, survival rate, and lung injury were examined. Results showed that leptin levels were predominantly increased in the lung, but also in the heart, liver, kidney, and adipose tissue after LPS adminiatration. Compared with wild-type mice, LPS- or OA-induced lung injury was worse and the survival rate was lower in ob/ob mice. Moreover, leptin deficiency promoted the release of proinflammatory cytokines. Exogenous administration of leptin reduced lethality in ob/ob mice and ameliorated lung injury partly through inhibiting the activation of NF-κB, p38, and ERK pathways. These results indicated that leptin deficiency contributed to the development of lung injury by enhancing inflammatory response, and a high level of leptin improved survival and protected against ALI.

  16. Natural antioxidant betanin protects rats from paraquat-induced acute lung injury interstitial pneumonia.

    Science.gov (United States)

    Han, Junyan; Ma, Deshun; Zhang, Miao; Yang, Xuelian; Tan, Dehong

    2015-01-01

    The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-α levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.

  17. [INFLUENCE OF LIPOSUCTION OF LARGE VOLUME ON SYSTEMIC AND LUNG CIRCULATION, OXIGENATED LUNG FUNCTION].

    Science.gov (United States)

    Nikolaeva, I P; Kapranova, A S; Popova, V B; Lodyagin, A N; Frolova, T A

    2015-01-01

    The authors measured the changes of hemodynamics in 72 patients. It was also estimated a blood oxygenation and volume of liquid sectors of the organism in different degree of obesity before and after liposuction of the large volume. It was shown, that this operation facilitated to an improvement of respiratory lung function due to changes of pulmonary circulation.

  18. Lung ultrasound and chest x-ray for detecting pneumonia in an acute geriatric ward

    OpenAIRE

    2016-01-01

    Abstract Background: Our aim was to compare the accuracy of lung ultrasound (LUS) and standard chest x-ray (CXR) for diagnosing pneumonia in older patients with acute respiratory symptoms (dyspnea, cough, hemoptysis, and atypical chest pain) admitted to an acute-care geriatric ward. Methods: We enrolled 169 (80 M, 89 F) multimorbid patients aged 83.0 ± 9.2 years from January 1 to October 31, 2015. Each participant underwent CXR and bedside LUS within 6 hours from ward admission. LUS was perfo...

  19. Hydroxysafflor yellow A suppress oleic acid-induced acute lung injury via protein kinase A

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chaoyun [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China); Huang, Qingxian [Department of Hepatobiliary Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000 (China); Wang, Chunhua; Zhu, Xiaoxi; Duan, Yunfeng; Yuan, Shuai [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China); Bai, Xianyong, E-mail: xybai2012@163.com [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China)

    2013-11-01

    Inflammation response and oxidative stress play important roles in acute lung injury (ALI). Activation of the cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of reactive oxygen species (ROS). Hydroxysafflor yellow A (HSYA) is a natural flavonoid compound that reduces oxidative stress and inflammatory cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial oxygen tension (PaO{sub 2}), carbon dioxide tension, pH, and the PaO{sub 2}/fraction of inspired oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The protein and inflammatory cytokine levels in the bronchoalveolar lavage fluid and serum were determined using enzyme-linked immunoassay. The activities of superoxide dismutase, glutathione peroxidase, PKA, and nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax, caspase 3, and p22{sup phox} levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating caspase 3, and reducing the Bcl-2/Bax ratio. H-89 increased these effects. HSYA significantly increased the activities of antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI. - Highlights: • Oleic acid (OA) cause acute lung injury (ALI) via inhibiting cAMP/PKA signal pathway. • Blocking protein kinase A (PKA) activation may

  20. Residential ozone and lung function in the elderly

    DEFF Research Database (Denmark)

    Braeuner, Elvira V.; Karottki, Dorina Gabriela; Frederiksen, Marie

    2016-01-01

    Ground level ozone arises primarily from traffic, it is a powerful oxidant and its primary target organ is the lung. Most epidemiological studies reporting the health effects of ozone have estimated individual exposure from measurements obtained from outdoor monitors but surrogates of personal...... exposure may not adequately reflect personal exposures. Also, the main focus has been on infants and children. Our purpose was to assess associations between urban background ozone and indoor residential ozone levels as well as to investigate the effects of indoor residential ozone on lung function in 51...... elderly non-smokers. Indoor ozone was measured passively in homes, while urban background outdoor ozone was monitored continuously at a fixed monitoring station located on the roof of the 20-m high university H.C. Ørsteds campus building in a park area. Lung function was measured at baseline as well...

  1. 17β-Estradiol administration attenuates seawater aspiration-induced acute lung injury in rats.

    Science.gov (United States)

    Fan, Qixin; Zhao, Pengtao; Li, Jiahuan; Xie, Xiaoyan; Xu, Min; Zhang, Yong; Mu, Deguang; Li, Wangping; Sun, Ruilin; Liu, Wei; Nan, Yandong; Zhang, Bo; Jin, Faguang; Li, Zhichao

    2011-12-01

    There is very little evidence on the value of administering estrogen in cases of seawater drowning which can induce acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether 17β-estradiol (E2) treatment can attenuate seawater aspiration-induced ALI in rats. In the experiment, ALI was induced by endotracheal instillation of seawater (4mL/kg) and the rats were then given intraperitoneal injection of E2 (5mg/kg) 20min after seawater instillation. Finally, the changes of arterial blood gases which contained hydrogen ion concentration (pH), arterial oxygen tension (PaO(2)) and arterial carbon dioxide tension (PaCO(2)) were measured and the measurement of extravascular lung water (EVLW) was observed. The pulmonary histological changes were evaluated by hematoxylin-eosin stain. The expression of aquaporins (AQPs) 1, AQP5, and estrogen receptor-β (ERβ) was measured by western blotting and immunohistochemical methods. The results showed that compared with normal saline water, seawater aspiration induced more serious ALI in rats which was markedly alleviated by E2 treatment. Meanwhile, the ERβ in lung tissues was activated after E2 administration. The seawater aspiration group also presented with severe pulmonary edema which was paralleled with over expressed AQP1 and AQP5. However, the up-regulation of AQP1 and AQP5 was suppressed by the administration of E2, resulting in an attenuation of lung edema. In conclusion, E2 treatment could effectively attenuate seawater aspiration-induced acute lung injury in rats by the down-regulation of AQP1 and AQP5.

  2. Role of Claudin Protein in Acute Lung Injury%Claudin蛋白在急性肺损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    刘梅; 邓星奇(综述); 李文放(审校)

    2015-01-01

    肺泡上皮直接与外界环境接触以进行气体交换,微小的上皮屏障的改变就可能增加肺部患某些疾病的敏感性。最近的研究已经把肺上皮屏障在肺相关疾病发生、发展中发挥的作用作为焦点(如急性肺损伤等)。尽管关于密封蛋白( Claudin )在肺部的功能及其调节机制还知之甚少,但越来越多的证据显示,急性肺损伤时外界环境的刺激会影响 Claudin蛋白的表达以及肺泡上皮屏障功能。该文就急性肺损伤时Claudin蛋白调节肺泡上皮屏障功能的最新研究进展予以综述。%Alveolar epithelium can have gas exchange by communicating with environment ,so it is easy to be hurt by the environment.The slight change of epithelial barrier may bring the sensitvity of lung disea-ses.Recent studies have been focusing on the development of lung epithelial barrier in the lung diseases ,such as acute lung injury.Although the underlying mechanisms of Claudin tight junction protein in lung diseases are still unclear,mounting evidences suggest that the expression of Claudin protein and the function of lung epithelial barrier can be influenced by the environment .Here is to make a review of the research progress in the function of Claudin protein regulating lung epithelial barrier in the acute lung injury .

  3. VEGF‐D promotes pulmonary oedema in hyperoxic acute lung injury

    OpenAIRE

    Sato, Teruhiko; Paquet‐Fifield, Sophie; Harris, Nicole C; Roufail, Sally; Turner, Debra J.; Yuan, Yinan; Zhang, You‐Fang; Fox, Stephen B; Hibbs, Margaret L.; Wilkinson‐Berka, Jennifer L; Williams, Richard A.; Stacker, Steven A.; Peter D Sly; Achen, Marc G.

    2016-01-01

    Abstract Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF‐D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF‐D in pathological oedema was unknown. To add...

  4. Pathogenesis of Septic Acute Lung Injury and Strategies for Immuno-Pharmacological Therapy.

    Science.gov (United States)

    1996-10-01

    obtained from septic-NO animals revealed a qualitative reduction in alveolar and septal edema . Although qualitative in nature, parenchyma of septic-NO...pulmonary edema in a model of acute lung injury. Am. Rev. Respir. Dis. 142:1083- 1087. 18. McDonald, R. J. 1991. Pentoxifylline reduces injury to isolated...patients with uncomplicated sepsis and septic shock--comparison with cardiogenic shock. Thromb. Haemost. 58:709-713. 60. Carvalho, A. C., S. DeMarinis

  5. Could erlotinib treatment lead to acute cardiovascular events in patients with lung adenocarcinoma after chemotherapy failure?

    Directory of Open Access Journals (Sweden)

    Kus T

    2015-06-01

    Full Text Available Tulay Kus, Gokmen Aktas, Alper Sevinc, Mehmet Emin Kalender, Celaletdin Camci Department of Internal Medicine, Division of Medical Oncology, Gaziantep University, Gaziantep, Turkey Abstract: Erlotinib, an epidermal growth factor receptor and tyrosine kinase inhibitor, is a targeted drug that was approved for the treatment of non-small-cell lung cancers and pancreatic cancers. Targeted tyrosine kinase inhibitors are known to have cardiotoxic effects. However, erlotinib does not have a statistically proven effect of increasing acute cardiovascular event (ACE risk. Preclinical studies showed that beta agonist stimulation among rats that were administered erlotinib led to cardiovascular damage. Thus, there would be an aggregate effect of erlotinib on ACE, although it is not thought to be a cardiotoxic drug itself. In this paper, we present two non-small-cell lung cancer cases that developed ACE under erlotinib treatment. Keywords: erlotinib, lung cancer, myocardial infarction, EGFR

  6. Analysis of regional compliance in a porcine model of acute lung injury.

    Science.gov (United States)

    Czaplik, Michael; Biener, Ingeborg; Dembinski, Rolf; Pelosi, Paolo; Soodt, Thomas; Schroeder, Wolfgang; Leonhardt, Steffen; Marx, Gernot; Rossaint, Rolf; Bickenbach, Johannes

    2012-10-15

    Lung protective ventilation in acute lung injury (ALI) focuses on using low tidal volumes and adequate levels of positive end-expiratory pressure (PEEP). Identifying optimal pressure is difficult because pressure-volume (PV) relations differ regionally. Precise analysis demands local measurements of pressures and related alveolar morphologies. In a porcine model of surfactant depletion (n=24), we combined measuring static pressures with endoscopic microscopy and electrical impedance tomography (EIT) to examine regional PV loops and morphologic heterogeneities between healthy (control group; CON) and ALI lungs ventilated with low (LVT) or high tidal volumes (HVT). Quantification included indices for microscopy (Volume Air Index (VAI), Heterogeneity and Circularity Index), EIT analysis and calculation of regional compliances due to generated PV loops. We found that: (1) VAI decreased in lower lobe after ALI, (2) electrical impedance decreased in dorsal regions and (3) PV loops differed regionally. Further studies should prove the potentials of these techniques on individual respiratory settings and clinical outcome.

  7. Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury

    Directory of Open Access Journals (Sweden)

    Maria Entezari

    2014-01-01

    Full Text Available Prolonged exposure to hyperoxia results in acute lung injury (ALI, accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1 in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to ≥99% O2 (hyperoxia significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1 caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP, inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation.

  8. Effects of biliverdin administration on acute lung injury induced by hemorrhagic shock and resuscitation in rats.

    Directory of Open Access Journals (Sweden)

    Junko Kosaka

    Full Text Available Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-α and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the

  9. Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib

    Directory of Open Access Journals (Sweden)

    Woodcock HV

    2013-06-01

    Full Text Available Hannah V Woodcock,1,2 Philip L Molyneaux,1,3 Toby M Maher1–31Interstitial Lung Disease Unit, Royal Brompton Hospital, 2Centre for Respiratory Research, University College London, 3National Heart and Lung Institute, Imperial College London, London, UKAbstract: Idiopathic pulmonary fibrosis (IPF is a chronic, progressive, fibrotic lung disease with no clear etiology and a paucity of therapeutic options. Nintedanib (previously known as BIBF 1120 is a tyrosine kinase receptor antagonist which inhibits a number of key receptors, including those for platelet derived growth factor (PDGF, vascular endothelial growth factor (VEGF, and fibroblast growth factor (FGF. These growth factors are profibrotic and each has been investigated as a potential standalone therapeutic target in IPF. Simultaneous inhibition of these receptors, with an analog of nintedanib, has proved to be effective in experimental animal models of pulmonary fibrosis. This observation, together with extensive safety and pharmacokinetic data from studies of nintedanib in malignancy, paved the way for the clinical development of this drug in IPF. The Phase IIb TOMORROW trial demonstrated that treatment with nintedanib may potentially slow decline in lung function, decrease the frequency of acute exacerbations, and improve quality of life in patients with IPF. While these observations are drawn from a single clinical trial, taken together with the preclinical data they suggest that nintedanib may yet become an important therapeutic option for individuals with IPF. The results of ongoing parallel, international, multicenter Phase III clinical trials are therefore eagerly awaited.Keywords: interstitial lung disease, BIBF 1120, clinical trials, usual interstitial pneumonia, acute exacerbation

  10. Hemorrhage and resuscitation induce alterations in cytokine expression and the development of acute lung injury.

    Science.gov (United States)

    Shenkar, R; Coulson, W F; Abraham, E

    1994-03-01

    Acute pulmonary injury occurs frequently following hemorrhage and injury. In order to better examine the sequence of events leading to lung injury in this setting, we investigated lung histology as well as in vivo mRNA levels for cytokines with proinflammatory and immunoregulatory properties (IL-1 beta, IL-6, IL-10, TNF-alpha, TGF-beta, IFN-gamma) over the 3 days following hemorrhage and resuscitation. Significant increases in mRNA levels for IL-1 beta, IL-6, IL-10, and IFN-gamma, but not TNF-alpha, were present among intraparenchymal pulmonary mononuclear cells obtained 1 and 3 days after hemorrhage. Among alveolar macrophages, TNF-alpha and IL-1 beta mRNA levels were increased 3 days after hemorrhage. Few changes in cytokine mRNA levels, with the exception of TNF-alpha at 3 days after hemorrhage, were present among peripheral blood mononuclear cells. Histologic examination of lungs from hemorrhaged animals showed no alterations 1 day after hemorrhage, but neutrophil and mononuclear cell infiltrates, edema, intra-alveolar hemorrhage, and fibrin generation were present 3 days after hemorrhage. These results suggest that hemorrhage-induced enhancement of proinflammatory cytokine gene transcription may be an important mechanism contributing to the frequent development of acute lung injury following blood loss and injury.

  11. Role of Kupffer cells in acute hemorrhagic necrotizing pancreatitis-associated lung injury of rats

    Institute of Scientific and Technical Information of China (English)

    Hong-Bin Liu; Nai-Qiang Cui; Dong-Hua Li; Chang Chen

    2006-01-01

    AIM: To investigate the role of Kupffer cells (KCs) in acute hemorrhagic necrotizing pancreatitis-associated lung injury (AHNP-LI).METHODS: Forty-two rats were allocated to four groups [sham operation, AHNP model, gadolinium chloride (GdCl3) pretreatment, GdCl3 control]. In GdCl3pretreatment group, GdCl3 was administered by caudal vein injection 24 h before the AHNP model induction.Blood from the iliac artery, alveolar macrophages and tissues from the pancreas and lung, were collected in six animals per group 3 and 6 h after acute pancreatitis induction. TNF-α, IL-1 of serum, myeloperoxidase (MPO)of lung tissue, NF-κB activation of alveolar macrophages were detected. Serum AST and ALT in sham operation group and GdCl3 control group were tested. In addition,histopathological changes of the pancreas and lung were observed under light microscope.RESULTS: MPO of lung tissue and TNF-α, IL-1 levels of serum were all reduced significantly in GdCl3pretreatment group compared to those in AHNP group(P<0.01). NF-κB activation of alveolar macrophages was also attenuated significantly in GdCl3 pretreatment group compared to that in AHNP group (P<0.01). The pathological injury of the lung was ameliorated obviously in GdCl3 pretreatment group compared to that in AHNP group. Nevertheless, the serum amylase level did not reduce and injury of the pancreas was not prevented in GdCl3 pretreatment group.CONCLUSION: Pulmonary injury induced by AHNP is mediated by KC activation and AHNP-LI can be significantly ameliorated by pretreatment with GdCl3 and KCs play a vital role in AHNP-LI.

  12. Clinical evaluation of sivelestat for acute lung injury/acute respiratory distress syndrome following surgery for abdominal sepsis

    Directory of Open Access Journals (Sweden)

    Tsuboko Y

    2012-10-01

    Full Text Available Yoshiaki Tsuboko,1 Shinhiro Takeda,1,2 Seiji Mii,1 Keiko Nakazato,1 Keiji Tanaka,2 Eiji Uchida,3 Atsuhiro Sakamoto11Department of Anesthesiology, Nippon Medical School, 2Intensive Care Unit and Cardiac Care Unit, Nippon Medical School Hospital, 3Department of Surgery, Nippon Medical School, Tokyo, JapanBackground: The efficacy of sivelestat in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS has not been established. In part, this is due to the wide variety of factors involved in the etiology of ALI/ARDS. In this study, we examined the efficacy of sivelestat in patients with ALI/ARDS associated with abdominal sepsis.Methods: The subjects were 49 patients with ALI/ARDS after surgery for abdominal sepsis. The efficacy of sivelestat was retrospectively assessed in two treatment groups, ie, a sivelestat group (n = 34 and a non-sivelestat group (n = 15.Results: The sivelestat group showed significant improvements in oxygenation, thrombocytopenia, and multiple organ dysfunction score. The number of ventilator days (6.6 ± 6.1 versus 11.1 ± 8.4 days; P = 0.034 and length of stay in the intensive care unit (8.5 ± 6.2 versus 13.3 ± 9.5 days; P = 0.036 were significantly lower in the sivelestat group. The hospital mortality rate decreased by half in the sivelestat group, but was not significantly different between the two groups.Conclusion: Administration of sivelestat to patients with ALI/ARDS following surgery for abdominal sepsis resulted in early improvements of oxygenation and multiple organ dysfunction score, early ventilator weaning, and early discharge from the intensive care unit.Keywords: sivelestat, acute lung injury, acute respiratory distress syndrome, abdominal sepsis

  13. Lung function, bronchial hyperresponsiveness, and atopy among firefighters

    NARCIS (Netherlands)

    Greven, Frans; Krop, Esmeralda; Spithoven, Jack; Rooyackers, Jos; Kerstjens, Huib; Heederik, Dick

    2011-01-01

    Objectives The aim of this study was to determine associations between lung function, bronchial hyperresponsiveness (BHR), and atopy with exposure to fire smoke among firefighters. Methods The study was comprised of 402 firefighters, a randomly chosen subset of a previous survey among firefighters i

  14. Genetics and Genomics of Longitudinal Lung Function Patterns in Asthmatics

    NARCIS (Netherlands)

    McGeachie, Michael J; Yates, Katherine P; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L; Van Natta, Mark L; Wise, Robert A; Szefler, Stanley J; Sharma, Sunita; Kho, Alvin T; Cho, Michael H; Croteau-Chonka, Damien C; Castaldi, Peter J; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A; Zeiger, Robert S; Adkinson, N Franklin; Williams, Paul V; Kelly, H William; Grasemann, Hartmut; Vonk, Judith M; Koppelman, Gerard H; Postma, Dirkje S; Raby, Benjamin A; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L; Tantisira, Kelan G; Silverman, Edwin K; Tonascia, James; Strunk, Robert C; Weiss, Scott T

    2016-01-01

    RATIONALE: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine the genetic und

  15. Integrative pathway genomics of lung function and airflow obstruction

    NARCIS (Netherlands)

    Gharib, Sina A.; Loth, Daan W.; Artigas, Maria Soler; Birkland, Timothy P.; Wilk, Jemma B.; Wain, Louise V.; Brody, Jennifer A.; Obeidat, Ma'en; Hancock, Dana B.; Tang, Wenbo; Rawal, Rajesh; Boezen, H. Marike; Imboden, Medea; Huffman, Jennifer E.; Lahousse, Lies; Alves, Alexessander C.; Manichaikul, Ani; Hui, Jennie; Morrison, Alanna C.; Ramasamy, Adaikalavan; Smith, Albert Vernon; Gudnason, Vilmundur; Surakka, Ida; Vitart, Veronique; Evans, David M.; Strachan, David P.; Deary, Ian J.; Hofman, Albert; Glaeser, Sven; Wilson, James F.; North, Kari E.; Zhao, Jing Hua; Heckbert, Susan R.; Jarvis, Deborah L.; Probst-Hensch, Nicole; Schulz, Holger; Barr, R. Graham; Jarvelin, Marjo-Riitta; O'Connor, George T.; Kahonen, Mika; Cassano, Patricia A.; Hysi, Pirro G.; Dupuis, Josee; Hayward, Caroline; Psaty, Bruce M.; Hall, Ian P.; Parks, William C.; Tobin, Martin D.; London, Stephanie J.

    2015-01-01

    Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating p

  16. Treatment of sepsis and ARDS with extracorporeal membrane oxygenation and interventional lung assist membrane ventilator in a patient with acute lymphoblastic leukemia.

    Science.gov (United States)

    Gorjup, Vojka; Fister, Misa; Noc, Marko; Rajic, Vladan; Ribaric, Suada Filekovic

    2012-07-01

    We report an 18-year-old ice skater with acute lymphoblast leukemia. She developed Staphylococcus epidermidis bacteremia, severe sepsis, septic shock, and ARDS following chemotherapy-induced severe bone marrow failure. She was successfully treated with extraordinary life support measures, which included extracorporeal membrane oxygenation, double lumen lung ventilation for management of hemoptysis, and lung assist membrane ventilation. After 57 days of ICU treatment and a year of rehabilitation, the patient has fully regained her functional status, is now finishing high school, and is ice skating again.

  17. Predicting functional recovery after acute ankle sprain.

    Directory of Open Access Journals (Sweden)

    Sean R O'Connor

    Full Text Available INTRODUCTION: Ankle sprains are among the most common acute musculoskeletal conditions presenting to primary care. Their clinical course is variable but there are limited recommendations on prognostic factors. Our primary aim was to identify clinical predictors of short and medium term functional recovery after ankle sprain. METHODS: A secondary analysis of data from adult participants (N = 85 with an acute ankle sprain, enrolled in a randomized controlled trial was undertaken. The predictive value of variables (age, BMI, gender, injury mechanism, previous injury, weight-bearing status, medial joint line pain, pain during weight-bearing dorsiflexion and lateral hop test recorded at baseline and at 4 weeks post injury were investigated for their prognostic ability. Recovery was determined from measures of subjective ankle function at short (4 weeks and medium term (4 months follow ups. Multivariate stepwise linear regression analyses were undertaken to evaluate the association between the aforementioned variables and functional recovery. RESULTS: Greater age, greater injury grade and weight-bearing status at baseline were associated with lower function at 4 weeks post injury (p<0.01; adjusted R square=0.34. Greater age, weight-bearing status at baseline and non-inversion injury mechanisms were associated with lower function at 4 months (p<0.01; adjusted R square=0.20. Pain on medial palpation and pain on dorsiflexion at 4 weeks were the most valuable prognostic indicators of function at 4 months (p< 0.01; adjusted R square=0.49. CONCLUSION: The results of the present study provide further evidence that ankle sprains have a variable clinical course. Age, injury grade, mechanism and weight-bearing status at baseline provide some prognostic information for short and medium term recovery. Clinical assessment variables at 4 weeks were the strongest predictors of recovery, explaining 50% of the variance in ankle function at 4 months. Further

  18. Midterm renal functions following acute renal infarction.

    Science.gov (United States)

    Ongun, Sakir; Bozkurt, Ozan; Demir, Omer; Cimen, Sertac; Aslan, Guven

    2015-10-01

    The aim of this study was to explore clinical features of renal infarction (RI) that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT) and at least 1 year follow-up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA) only, whereas patients with atrial fibrillation (AF) or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR) referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD) formula. Twenty-seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8%) with RI had atrial fibrillation (AF) as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9%) had elevated serum lactate dehydrogenase (LDH), 18 patients (78.2%) had leukocytosis, and 16 patients (69.5%) had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m(2) at admission and increased to 82.3 ± 23.4 mL/min/1.73 m(2) at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.

  19. Effect of inhalation of nebulized NO donor substance on acute hypoxic lung injury in newborn piglets

    Institute of Scientific and Technical Information of China (English)

    XIA Hong-ping; HUANG Guo-ying; ZHU Jian-xing; SUN Bo

    2008-01-01

    Background Birth asphyxia may result in multiple organ dysfunction such as lung injury.Inhalation of nebulized nitric oxide precursor can selectively reduce pulmonary hypertension.However,it is unknown whether such precursors can alleviate lung injury induced by hypoxia.We evaluated the effect of inhalation of nebulized nitroglycerine and sodium nitroprusside on acute hypoxic lung injury in newborn piglets.Methods Acute hypoxic lung injury was induced by inspiring 10% O2 for 1 hour.Twenty-four anaesthetized and mechanically ventilated piglets (5-7 days old) were randomly divided into four groups:(1) group S,not hypoxic;(2) group C,nebulized saline after hypoxia;(3) group NTG,nebulized nitroglycerine after hypoxia;(4) group SNP,nebulized sodium nitroprusside after hypoxia.Respiratory dynamic compliance and resistance of respiratory system were recorded at baseline,0.5 hour and 1 hour of hypoxia;then 0.5 hour,1 hour,3 hours and 5 hours following hypoxia.After nebulization,arterial blood was collected for measuring methaemoglobin and nitrate/nitrite levels.Right lung tissue,wet-dry ratio and myeloperoxidase level were determined.White blood cell count (WBC),total surfactant phospholipids (TPL) and disaturated phosphatidyl choline (DSPC) of the bronchoalveolar lavage fluid (BALF) were calculated,Left lungs were used for examining pathological changes.Results No significant difference was observed in respiratory dynamic compliance,resistance of respiratory system,wet-dry ratio,levels of methaemoglobin and nitrate/nitrite after nebulization,TPL or DSPC/TPL among four groups.WBC in BALF in groups NTG and SNP significantly decreased as compared with group C:similarly for myeloperoxidase level in lung tissue.Lung histological findings showed infiltration of neutrophils in groups NTG and SNP decreased significantly as compared with group C.Conclusion Inhalation of nebulized nitroglycerine or sodium nitroprusside can alleviate the infiltration of neutrophils,while it affects

  20. DNaseI Protects against Paraquat-Induced Acute Lung Injury and Pulmonary Fibrosis Mediated by Mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Guo Li

    2015-01-01

    Full Text Available Background. Paraquat (PQ poisoning is a lethal toxicological challenge that served as a disease model of acute lung injury and pulmonary fibrosis, but the mechanism is undetermined and no effective treatment has been discovered. Methods and Findings. We demonstrated that PQ injures mitochondria and leads to mtDNA release. The mtDNA mediated PBMC recruitment and stimulated the alveolar epithelial cell production of TGF-β1 in vitro. The levels of mtDNA in circulation and bronchial alveolar lavage fluid (BALF were elevated in a mouse of PQ-induced lung injury. DNaseI could protect PQ-induced lung injury and significantly improved survival. Acute lung injury markers, such as TNFα, IL-1β, and IL-6, and marker of fibrosis, collagen I, were downregulated in parallel with the elimination of mtDNA by DNaseI. These data indicate a possible mechanism for PQ-induced, mtDNA-mediated lung injury, which may be shared by other causes of lung injury, as suggested by the same protective effect of DNaseI in bleomycin-induced lung injury model. Interestingly, increased mtDNA in the BALF of patients with amyopathic dermatomyositis-interstitial lung disease can be appreciated. Conclusions. DNaseI targeting mtDNA may be a promising approach for the treatment of PQ-induced acute lung injury and pulmonary fibrosis that merits fast tracking through clinical trials.

  1. Dietary phosphorus acutely impairs endothelial function.

    Science.gov (United States)

    Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

    2009-07-01

    Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

  2. Allergic airway inflammation decreases lung bacterial burden following acute Klebsiella pneumoniae infection in a neutrophil- and CCL8-dependent manner.

    Science.gov (United States)

    Dulek, Daniel E; Newcomb, Dawn C; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P; Blackwell, Timothy S; Moore, Martin L; Boyd, Kelli L; Kolls, Jay K; Peebles, R Stokes

    2014-09-01

    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity.

  3. Intestinal epithelium is more susceptible to cytopathic injury and altered permeability than the lung epithelium in the context of acute sepsis.

    Science.gov (United States)

    Julian, Mark W; Bao, Shengying; Knoell, Daren L; Fahy, Ruairi J; Shao, Guohong; Crouser, Elliott D

    2011-10-01

    Mitochondrial morphology and function are altered in intestinal epithelia during endotoxemia. However, it is unclear whether mitochondrial abnormalities occur in lung epithelial cells during acute sepsis or whether mitochondrial dysfunction corresponds with altered epithelial barrier function. Thus, we hypothesized that the intestinal epithelium is more susceptible to mitochondrial injury than the lung epithelium during acute sepsis and that mitochondrial dysfunction precedes impaired barrier function. Using a resuscitated feline model of Escherichia coli-induced sepsis, lung and ileal tissues were harvested after 6 h for histological and mitochondrial ultrastructural analyses in septic (n = 6) and time-matched controls (n = 6). Human lung epithelial cells (HLEC) and Caco-2 monolayers (n = 5) were exposed to 'cytomix' (TNFα: 40 ng/ml, IL-1β: 20 ng/ml, IFNγ: 10 ng/ml) for 24-72 h, and measurements of transepithelial electrical resistance (TER), epithelial permeability and mitochondrial membrane potential (ΔΨ) were taken. Lung epithelial morphology, mitochondrial ultrastructure and pulmonary gas exchange were unaltered in septic animals compared to matching controls. While histologically intact, ileal epithelia demonstrated marked mitochondrial ultrastructural damage during sepsis. Caco-2 monolayers treated with cytomix showed a significant decrease in mitochondrial ΔΨ within 24 h, which was associated with a progressive reduction in TER and increased epithelial permeability over the subsequent 48 h. In contrast, mitochondrial ΔΨ and epithelial barrier functions were preserved in HLEC following cytomix. These findings indicate that intestinal epithelium is more susceptible to mitochondrial damage and dysfunction than the lung epithelium in the context of sepsis. Early alterations in mitochondrial function portend subsequent epithelial barrier dysfunction.

  4. A multivariate analysis of serum nutrient levels and lung function

    Directory of Open Access Journals (Sweden)

    Smit Henriette A

    2008-09-01

    Full Text Available Abstract Background There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1. Methods Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis. Results In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E, selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1. Higher concentrations of potassium and sodium were associated with lower FEV1. Conclusion Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation.

  5. Resveratrol ameliorates LPS-induced acute lung injury via NLRP3 inflammasome modulation.

    Science.gov (United States)

    Jiang, Lei; Zhang, Lei; Kang, Kai; Fei, Dongsheng; Gong, Rui; Cao, Yanhui; Pan, Shangha; Zhao, Mingran; Zhao, Mingyan

    2016-12-01

    NLRP3 inflammasome plays a pivotal role in the development of acute lung injury (ALI), accelerating IL-1β and IL-18 release and inducing lung inflammation. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in lipopolysaccharide-induced ALI. Mice were intratracheally instilled with 3mg/kg lipopolysaccharide (LPS) to induce ALI. Resveratrol treatment alleviated the LPS-induced lung pathological damage, lung edema and neutrophil infiltration. In addition, resveratrol reversed the LPS-mediated elevation of IL-1β and IL-18 level in the BAL fluids. In lung tissue, resveratrol also inhibited the LPS-induced NLRP3, ASC, caspase-1 mRNA and protein expression, and NLRP3 inflammasome activation. Moreover, resveratrol administration not only suppressed the NF-κB p65 nuclear translocation, NF-κB activity and ROS production in the LPS-treated mice, but also inhibited the LPS-induced thioredoxin-interacting protein (TXNIP) protein expression and interaction of TXNIP-NLRP3 in lung tissue. Meanwhile, resveratrol obviously induced SIRT1 mRNA and protein expression in the LPS-challenged mice. Taken together, our study suggests that resveratrol protects against LPS-induced lung injury by NLRP3 inflammasome inhibition. These findings further suggest that resveratrol may be of great value in the treatment of ALI and a potential and an effective pharmacological agent for inflammasome-relevant diseases.

  6. Effects of low potassium dextran glucose solution on oleic acid-induced acute lung injury in juvenile piglets

    Institute of Scientific and Technical Information of China (English)

    LING Feng; LIU Ying-long; LIU Ai-jun; WANG Dong; WANG Qiang

    2011-01-01

    Background Epithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution (LPD) have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets.Methods Oleic acid (0.1 ml/kg) was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups (n=5 each): oleic acid-induced group (control group) with intravenous infusion of 12.5 ml/kg of lactated Ringer's solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD (12.5 ml/kg) 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury.Results Compared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio,partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved (P<0.05or 0.01). Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group (P<0.05). Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group (P<0.05).Conclusions Before lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.

  7. Regulation of immunoproteasome function in the lung

    NARCIS (Netherlands)

    Keller, I.E.; Vosyka, O.; Takenaka, S.; Kloss, A.; Dahlmann, B.; Willems, L.I.; Verdoes, M.; Overkleeft, H.S.; Marcos, E.; Adnot, S.; Hauck, S.M.; Ruppert, C.; Gunther, A.; Herold, S.; Ohno, S.; Adler, H.; Eickelberg, O.; Meiners, S.

    2015-01-01

    Impaired immune function contributes to the development of chronic obstructive pulmonary disease (COPD). Disease progression is further exacerbated by pathogen infections due to impaired immune responses. Elimination of infected cells is achieved by cytotoxic CD8(+) T cells that are activated by MHC

  8. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  9. Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia-reperfusion in mice: role of Nrf2.

    Science.gov (United States)

    Meng, Qing-Tao; Cao, Chen; Wu, Yang; Liu, Hui-Min; Li, Wei; Sun, Qian; Chen, Rong; Xiao, Yong-Guang; Tang, Ling-Hua; Jiang, Ying; Leng, Yan; Lei, Shao-Qing; Lee, Chris C; Barry, Devin M; Chen, Xiangdong; Xia, Zhong-Yuan

    2016-10-01

    Intestinal ischemic post-conditioning (IPo) protects against lung injury induced by intestinal ischemia-reperfusion (IIR) partly through promotion of expression and function of heme oxygenase-1 (HO-1). NF-E2-related factor-2 (Nrf2) is a key transcription factor that interacts with HO-1 and regulates antioxidant defense. However, the role of Nrf2 in IPo protection of IIR-induced pulmonary injury is not completely understood. Here we show that IPo significantly attenuated IIR-induced lung injury and suppressed oxidative stress and systemic inflammatory responses. IPo also increased the expression of both Nrf2 and HO-1. Consistently, the beneficial effects of IPo were abolished by ATRA and Brusatol, potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ showed similar activity as IPo. Taken together, our data suggest that Nrf2 activity, along with HO-1, plays an important role in the protective effects of IPo against IIR-induced acute lung injury.

  10. Acute abdomen in a patient with paraesophageal hernia, resulting in acute compromised respiratory function

    DEFF Research Database (Denmark)

    Mekhael, Mira Rober; El-Hussuna, Alaa

    2017-01-01

    INTRODUCTION: We present a case of acute abdomen, causing increased intra-abdominal pressure, leading to further herniation of an existing paraesophageal hernia, and consequently acute compromised respiratory function. This acute respiratory complication to a paraesophageal hernia has not previou......INTRODUCTION: We present a case of acute abdomen, causing increased intra-abdominal pressure, leading to further herniation of an existing paraesophageal hernia, and consequently acute compromised respiratory function. This acute respiratory complication to a paraesophageal hernia has...... if complicated by acute abdomen. These patients could benefit from elective hernia repair, rather than watchful waiting, as it would eliminate pulmonary symptoms and prevent similar cases. Patients monitored using watchful waiting should be informed that acute abdomen could cause acute compromised respiratory...... function. CONCLUSION: Any case of acute abdomen causing high intra-abdominal pressure could potentially cause further herniation of an existing paraesophageal hernia, resulting in acute compromised respiratory function. In patients known to have a paraesophageal hernia, similar cases should be suspected...

  11. Reduction of Pulmonary Function After Surgical Lung Resections of Different Volume

    OpenAIRE

    Cukic, Vesna

    2014-01-01

    Introduction: In recent years an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused with common etiologic factor - smoking cigarettes. Objective: To determine how big the loss of lung function is after surgical resection of lung of different range. Methods: The study was done on 58 patients operated at the Clinic for thoracic surgery KCU Sarajevo, previously treated at th...

  12. Establishment of the critical period of severe acute pancreatitis-associated lung injury

    Institute of Scientific and Technical Information of China (English)

    Yi-Peng Chen; Jian-Wen Ning; Feng Ji

    2009-01-01

    BACKGROUND: Since respiratory dysfunction is the main cause of death in patients with severe acute pancreatitis (SAP), elucidating the critical period of acute pancreatitis-associated lung injury (APALI) is of important clinical value. This study aimed to define the risk period of APALI by a series of studies including a dynamic analysis of total water content, ultrastructure and number of type Ⅱ alveolar epithelial cells, and reactive oxygen metabolites (ROMs) of lung tissue in a mouse model of SAP, and a clinical analysis of APALI patients. METHODS: ICR mice were selected to establish a SAP model. They were given 7 intraperitoneal injections of cerulein (50 μg/kg body weight) at hourly intervals, followed by an intraperitoneal injection of lipopolysaccharide (15 mg/kg body weight). The total water content, ultrastructure, and number of type Ⅱ alveolar epithelial cells, and ROMs of lung tissue were assessed before (0 hour) and after the establishment of SAP model (6 hours, 12 hours, 1 day, 4 days, and 7 days). In addition, we analyzed the data from 215 patients with APALI (PaO2 RESULTS: The total water content and ultrastructure of type Ⅱ alveolar epithelial cells (mitochondria and lamellar bodies) of the lung in the SAP mice were significantly altered at 12 hours after the establishment of SAP model, and reached a maximum at 1 to 4 days. The number of type Ⅱ alveolar epithelial cells and ROMs increased maximally at 1 day after the establishment of the model. Furthermore, clinical results showed that lung injury occurred at a mean of 3.1435±1.0199 days in patients with SAP. These clinical data were almost consistent with the results of the SAP model. CONCLUSION: The risk period for APALI is between the first and fourth day during the course of SAP.

  13. Hydrogen sulfide donor regulates alveolar epithelial cell apoptosis in rats with acute lung injury

    Institute of Scientific and Technical Information of China (English)

    LIU Wen-li; LIU Zhi-wei; LI Tian-shui; WANG Cong; ZHAO Bin

    2013-01-01

    Background Acute lung injury (ALl) is a common syndrome associated with high morbidity and mortality in emergency medicine.Cell apoptosis plays a key role in the pathogenesis of ALl.Hydrogen sulfide (H2S) plays a protective role during acute lung injury.We designed this study to examine the role of H2S in the lung alveolar epithelial cell apoptosis in rats with ALl.Methods Sixty-nine male Sprague Dawley rats were used.ALl was induced by intra-tail vein injection of oleic acid (OA).NaHS solution was injected intraperitonally 30 minutes before OA injection as the NaHS pretreatment group.Single sodium hydrosulfide pretreatment group and control group were designed.Index of quantitative assessment (IQA),wet/dry weight (W/D) ratio and the percentage of polymorphonuclear leukocyte (PMN) cells in the bronchoalveolar lavage fluid (BALF) were determined.H2S level in lung tissue was measured by a sensitive sulphur electrode.Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Fas protein was measured by immunohistochemical staining.Results The level of endogenous H2S in lung tissue decreased with the development of ALl induced by OA injection.Apoptosis and Fas protein in alveolar epithelial cells increased in the ALl of rats but NaHS lessened apoptosis and Fas protein expression in alveolar epithelial cells of rats with ALl.Conclusion Endogenous H2S protects rats from oleic acid-induced ALl,probably by inhibiting cell apoptosis.

  14. Long-term change in pulmonary function after definitive radiotherapy for non-small cell lung cancer

    DEFF Research Database (Denmark)

    Schytte, T.; Bentzen, S. M.; Brink, C.

    2015-01-01

    with 3063 pairs of pulmonary function test (PFTs) were screened for eligibility for inclusion in the analysis of late changes in PF. To be eligible, patients had at least 3 PFTs after baseline. In this study, baseline was defined as 12 months after RT commencement to overcome a possible effect of tumor...... shrinkage and the acute side effect, radiation induced pneumonitis. PFT within 6 months prior to thoracic progression were excluded. The final study group comprised 106 patients with 1286 pairs of PFTs. For each patient complete dosimetric data, including GTV, PTV, mean lung dose, Vx for total lung volume...

  15. Lung clearance of /sup 99m/Tc-DTPA in patients with acute lung injury and pulmonary edema

    Energy Technology Data Exchange (ETDEWEB)

    Coates, G.; O' Brodovich, H.; Dolovich, M.

    1988-07-01

    Several acute and chronic conditions that alter the integrity of the pulmonary epithelium increased the rate of absorption or clearance into the circulation of small solutes deposited in the alveoli. Technetium 99m diethylenetriamine pentaacetic acid can be deposited in the lungs as a submicronic aerosol and its rate of clearance measured with a gamma camera or simple probe. This clearance technique is currently being used to evaluate patients who have developed pulmonary edema and also to detect those patients from a high risk group who are likely to develop adult respiratory distress syndrome (ARDS). Its role in the evaluation of patients with pulmonary edema is still under active investigation. It is clear that a single measurement in patients who smoke is not useful, but repeated measurements may provide important information. The lung clearance measurement is very sensitive to changes in epithelial integrity but is not specific for ARDS. It may be most useful in combination with other predictive tests or when the clearance rate is normal. 54 references.

  16. Low cognitive ability in early adulthood is associated with reduced lung function in middle age

    DEFF Research Database (Denmark)

    Carroll, Douglas; Batty, G David; Mortensen, Laust Hvas;

    2011-01-01

    Reduced lung function has been linked to poorer cognitive ability later in life. In the present study, the authors examined the converse: whether there was a prospective association between cognitive ability in early adulthood and lung function in middle age....

  17. Protective effects of pretreatment with Radix Paeoniae Rubra on acute lung injury induced by intestinal ischemia/ reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Chang; ZHANG Fan; XIA Zhong-yuan; LIN Hui; MO An-sheng

    2008-01-01

    Objective: To investigate the effect of pretreatment with Radix Paeoniae Rubra (RPR) on acute lung injury induced by intestinal ischemia/reperfusion in rats and its protective mechanism.Methods:n lung tissues was detected by immunohistochemistry and morphometry computer image analysis. Arterial blood gas analysis, lung permeability index, malondialdehyde (MDA) and superoxide dismutase (SOD) contents in lungs were measured. The histological changes of lung tissue were observed under light microscope.Results:The expression of HO-1 in RPR-pretreatment group and hemin group was obviously higher than that in sham-operation group and I/R group (P < 0.01). The level of MDA and lung permeability index in RPR-pretreatment and hemin group were significantly lower than those in I/R group (P<0.01 or P<0.05), while the activity of SOD in RPR-pretreatment and hemin group was obviously higher than that in I/R group (P<0.01 ). Under light microscope, the pathologic changes induced by I/R were significantly attenuated by RPR.Conclusion : Intestinal ischemia/reperfusion may result in acute lung injury and pretreatment with RPR injection can attenuate the injury. The protective effect of RPR on the acute lung injury is related to its property of inducing HO-1 expression and inhibiting lipid peroxidation.

  18. Evaluation of total and regional lung function using {sup 133}Xe dynamic ventilation SPECT and a comparison with the lung function test

    Energy Technology Data Exchange (ETDEWEB)

    Kan, Yongjin; Shinozuka, Akira; Takenaka, Hiroki; Munechika, Hirotsugu [Showa Univ., Tokyo (Japan). School of Medicine

    2001-08-01

    A lung dynamic SPECT study using {sup 133}Xe gas was performed a functional map created be region. The time activity curve (TAC) of each voxel was obtained from subsequent SPECT data. Washout rate (K) was calculated from TAC. The product of K and counter weighted voxel volume was defined as the lung function index (LFI). Using these 3 parameters (functional volume, K, and LFI) a function map was created. The sum of LFI was defined as total lung functional index (TLFI). Five healthy volunteers and 20 patients with various lung diseases were investigated. TLFI correlated well with FEV{sub 1.0} and MMF, and mean K with FEV{sub 1.0}%. The results indicate that a functional map obtained from lung dynamic SPECT is useful in estimating both resional and whole lung function. (author)

  19. Magnetic resonance lung function – a breakthrough for lung imaging and functional assessment? A phantom study and clinical trial

    Directory of Open Access Journals (Sweden)

    Rauh Manfred

    2006-08-01

    Full Text Available Abstract Background Chronic lung diseases are a major issue in public health. A serial pulmonary assessment using imaging techniques free of ionizing radiation and which provides early information on local function impairment would therefore be a considerably important development. Magnetic resonance imaging (MRI is a powerful tool for the static and dynamic imaging of many organs. Its application in lung imaging however, has been limited due to the low water content of the lung and the artefacts evident at air-tissue interfaces. Many attempts have been made to visualize local ventilation using the inhalation of hyperpolarized gases or gadolinium aerosol responding to MRI. None of these methods are applicable for broad clinical use as they require specific equipment. Methods We have shown previously that low-field MRI can be used for static imaging of the lung. Here we show that mathematical processing of data derived from serial MRI scans during the respiratory cycle produces good quality images of local ventilation without any contrast agent. A phantom study and investigations in 85 patients were performed. Results The phantom study proved our theoretical considerations. In 99 patient investigations good correlation (r = 0.8; p ≤ 0.001 was seen for pulmonary function tests and MR ventilation measurements. Small ventilation defects were visualized. Conclusion With this method, ventilation defects can be diagnosed long before any imaging or pulmonary function test will indicate disease. This surprisingly simple approach could easily be incorporated in clinical routine and may be a breakthrough for lung imaging and functional assessment.

  20. Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome.

    Science.gov (United States)

    Zhang, Yong; Li, Xiru; Grailer, Jamison J; Wang, Na; Wang, Mingming; Yao, Jianfei; Zhong, Rui; Gao, George F; Ward, Peter A; Tan, Dun-Xian; Li, Xiangdong

    2016-05-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are clinically severe respiratory disorders, and there are currently no Food and Drug Administration-approved drug therapies. Melatonin is a well-known anti-inflammatory molecule, which has proven to be effective in ALI induced by many conditions. Emerging studies suggest that the NLRP3 inflammasome plays a critical role during ALI. How melatonin directly blocks activation of the NLRP3 inflammasome in ALI remains unclear. In this study, using an LPS-induced ALI mouse model, we found intratracheal (i.t.) administration of melatonin markedly reduced the pulmonary injury and decreased the infiltration of macrophages and neutrophils into lung. During ALI, the NLRP3 inflammasome is significantly activated with a large amount of IL-1β and the activated caspase-1 occurring in the lung. Melatonin inhibits the activation of the NLRP3 inflammasome by both suppressing the release of extracellular histones and directly blocking histone-induced NLRP3 inflammasome activation. Notably, i.t. route of melatonin administration opens a more efficient therapeutic approach for treating ALI.

  1. Effects of Liver × receptor agonist treatment on signal transduction pathways in acute lung inflammation

    Directory of Open Access Journals (Sweden)

    Bramanti Placido

    2010-02-01

    Full Text Available Abstract Background Liver × receptor α (LXRα and β (LXRβ are members of the nuclear receptor super family of ligand-activated transcription factors, a super family which includes the perhaps better known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. There is limited evidence that LXL activation may reduces acute lung inflammation. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of carrageenan-induced pleurisy. Methods Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx, tumor necrosis factor-α, (TNF-α and interleukin-1β (IL-1β. Furthermore, carrageenan induced the expression of iNOS, nitrotyrosine and PARP, as well as induced apoptosis (TUNEL staining and Bax and Bcl-2 expression in the lung tissues. Results Administration of T0901317, 30 min after the challenge with carrageenan, caused a significant reduction in a dose dependent manner of all the parameters of inflammation measured. Conclusions Thus, based on these findings we propose that LXR ligand such as T0901317, may be useful in the treatment of various inflammatory diseases.

  2. Antiplatelet antibody may cause delayed transfusion-related acute lung injury

    Directory of Open Access Journals (Sweden)

    Torii Y

    2011-09-01

    Full Text Available Yoshitaro Torii1, Toshiki Shimizu1, Takashi Yokoi1, Hiroyuki Sugimoto1, Yuichi Katashiba1, Ryotaro Ozasa1, Shinya Fujita1, Yasushi Adachi2, Masahiko Maki3, Shosaku Nomura11The First Department of Internal Medicine, Kansai Medical University, Osaka, 2Department of Clinical Pathology, Toyooka Hospital, Hyogo, 3First Department of Pathology, Kansai Medical University, Osaka, JapanAbstract: A 61-year-old woman with lung cancer developed delayed transfusion-related acute lung injury (TRALI syndrome after transfusion of plasma- and leukoreduced red blood cells (RBCs for gastrointestinal bleeding due to intestinal metastasis. Acute lung injury (ALI recurred 31 days after the first ALI episode. Both ALI episodes occurred 48 hours after transfusion. Laboratory examinations revealed the presence of various antileukocyte antibodies including antiplatelet antibody in the recipient's serum but not in the donors' serum. The authors speculate that antiplatelet antibodies can have an inhibitory effect in the recipient, which can modulate the bona fide procedure of ALI and lead to a delay in the onset of ALI. This case illustrates the crucial role of a recipient's platelets in the development of TRALI.Keywords: delayed TRALI syndrome, recurrence, anti-platelet antibody

  3. Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury

    Science.gov (United States)

    Zhang, Fan; Li, Mian-yang; Lan, Ya-ting; Wang, Cheng-bin

    2016-01-01

    T helper (Th) 17 cells and CD4+ CD25+ regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury. Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h). We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology. Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-β and IL-23). Meanwhile, Treg prevalence and related cytokines (IL-10, IL-2 and IL-35) were decreased. Consequently, the ratio of Th17/Treg was higher after smoke inhalation. Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation. In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease. PMID:26884314

  4. Proinflammatory role of inducible nitric oxide synthase in acute hyperoxic lung injury

    Directory of Open Access Journals (Sweden)

    Kupatt Christian

    2004-09-01

    Full Text Available Abstract Background Hyperoxic exposures are often found in clinical settings of respiratory insufficient patients, although oxygen therapy (>50% O2 can result in the development of acute hyperoxic lung injury within a few days. Upon hyperoxic exposure, the inducible nitric oxide synthase (iNOS is activated by a variety of proinflammatory cytokines both in vitro and in vivo. In the present study, we used a murine hyperoxic model to evaluate the effects of iNOS deficiency on the inflammatory response. Methods Wild-type and iNOS-deficient mice were exposed to normoxia, 60% O2 or >95% O2 for 72 h. Results Exposure to >95% O2 resulted in an increased iNOS mRNA and protein expression in the lungs from wild-type mice. No significant effects of iNOS deficiency on cell differential in bronchoalveolar lavage fluid were observed. However, hyperoxia induced a significant increase in total cell count, protein concentration, LDH activity, lipid peroxidation, and TNF-α concentration in the bronchoalveolar lavage fluid compared to iNOS knockout mice. Moreover, binding activity of NF-κB and AP-1 appeared to be higher in wild-type than in iNOS-deficient mice. Conclusion Taken together, our results provide evidence to suggest that iNOS plays a proinflammatory role in acute hyperoxic lung injury.

  5. Lung T lymphocyte trafficking and activation during ischemic acute kidney injury.

    Science.gov (United States)

    Lie, Mihaela L; White, Laura E; Santora, Rachel J; Park, Jong M; Rabb, Hamid; Hassoun, Heitham T

    2012-09-15

    Despite advances in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely owing to extrarenal organ dysfunction. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that facilitate organ crosstalk and induce caspase-dependent lung apoptosis and injury through a TNFR1-dependent pathway. Given that T lymphocytes mediate local IRI in the kidney and are known to drive TNFR1-mediated apoptosis, we hypothesized that T lymphocytes activated during kidney IRI would traffic to the lung and mediate pulmonary apoptosis during AKI. In an established murine model of kidney IRI, we identified trafficking of CD3+ T lymphocytes to the lung during kidney IRI by flow cytometry and immunohistochemistry. T lymphocytes were primarily of the CD3+CD8+ phenotype; however, both CD3+CD4+ and CD3+CD8+ T lymphocytes expressed CD69 and CD25 activation markers during ischemic AKI. The activated lung T lymphocytes did not demonstrate an increased expression of intracellular TNF-α or surface TNFR1. Kidney IRI induced pulmonary apoptosis measured by caspase-3 activation in wild-type controls, but not in T cell-deficient (T(nu/nu)) mice. Adoptive transfer of murine wild-type T lymphocytes into T(nu/nu) mice restored the injury phenotype with increased cellular apoptosis and lung microvascular barrier dysfunction, suggesting that ischemic AKI-induced pulmonary apoptosis is T cell dependent. Kidney-lung crosstalk during AKI represents a complex biological process, and although T lymphocytes appear to serve a prominent role in the interorgan effects of AKI, further experiments are necessary to elucidate the specific role of activated T cells in modulating pulmonary apoptosis.

  6. Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury.

    Science.gov (United States)

    Yang, Lei; Li, Dihua; Zhuo, Yuzhen; Zhang, Shukun; Wang, Ximo; Gao, Hongwei

    2016-10-01

    In current study, we investigated the role of liriodendrin, a constituent isolated from Sargentodoxa cuneata (Oliv.) Rehd. Et Wils (Sargentodoxaceae), in cecal ligation and puncture (CLP)-induced acute lung inflammatory response and injury (ALI). The inflammatory mediator levels in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay (ELISA). Pathologic changes in lung tissues were evaluated via pathological section with hematoxylin and eosin (H&E) staining. To investigate the mechanism whereby liriodendrin regulates lung inflammation, the phosphorylation of the NF-kB (p65) and expression of vascular endothelial growth factor (VEGF) were determined by western blot assay. We show that liriodendrin treatment significantly improved the survival rate of mice with CLP-induced sepsis. Pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration were markedly decreased by liriodendrin. In addition, liriodendrin decreased the production of the proinflammatory mediators including (TNF-α, IL-1β, MCP-1, and IL-6) in lung tissues. Vascular permeability and lung myeloperoxidase (MPO) accumulation in the liriodendrin-treated mice were substantially reduced. Moreover, liriodendrin treatment significantly suppressed the expression of VEGF and activation of NF-kB in the lung. We further show that liriodendrin significantly reduced the production of proinflammatory mediators and downregulated NF-kB signaling in LPS-stimulated RAW 264.7 macrophage cells. Moreover, liriodendrin prevented the generation of reactive oxygen species (ROS) by upregulating the expression of SIRT1 in RAW 264.7 cells. These findings provide a novel theoretical basis for the possible application of liriodendrin in clinic.

  7. Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment.

    Science.gov (United States)

    Garibaldi, Brian T; D'Alessio, Franco R; Mock, Jason R; Files, D Clark; Chau, Eric; Eto, Yoshiki; Drummond, M Bradley; Aggarwal, Neil R; Sidhaye, Venkataramana; King, Landon S

    2013-01-01

    Acute lung injury (ALI) causes significant morbidity and mortality. Fibroproliferation in ALI results in worse outcomes, but the mechanisms governing fibroproliferation remain poorly understood. Regulatory T cells (Tregs) are important in lung injury resolution. Their role in fibroproliferation is unknown. We sought to identify the role of Tregs in ALI fibroproliferation, using a murine model of lung injury. Wild-type (WT) and lymphocyte-deficient Rag-1(-/-) mice received intratracheal LPS. Fibroproliferation was characterized by histology and the measurement of lung collagen. Lung fibrocytes were measured by flow cytometry. To dissect the role of Tregs in fibroproliferation, Rag-1(-/-) mice received CD4(+)CD25(+) (Tregs) or CD4(+)CD25(-) Tcells (non-Tregs) at the time of LPS injury. To define the role of the chemokine (C-X-C motif) ligand 12 (CXCL12)-CXCR4 pathway in ALI fibroproliferation, Rag-1(-/-) mice were treated with the CXCR4 antagonist AMD3100 to block fibrocyte recruitment. WT and Rag-1(-/-) mice demonstrated significant collagen deposition on Day 3 after LPS. WT mice exhibited the clearance of collagen, but Rag-1(-/-) mice developed persistent fibrosis. This fibrosis was mediated by the sustained epithelial expression of CXCL12 (or stromal cell-derived factor 1 [SDF-1]) that led to increased fibrocyte recruitment. The adoptive transfer of Tregs resolved fibroproliferation by decreasing CXCL12 expression and subsequent fibrocyte recruitment. Blockade of the CXCL12-CXCR4 axis with AMD3100 also decreased lung fibrocytes and fibroproliferation. These results indicate a central role for Tregs in the resolution of ALI fibroproliferation by reducing fibrocyte recruitment along the CXCL12-CXCR4 axis. A dissection of the role of Tregs in ALI fibroproliferation may inform the design of new therapeutic tools for patients with ALI.

  8. CT Manifestations of Lung Changes and Complications in Patients with Severe Acute Respiratory Syndrome

    Institute of Scientific and Technical Information of China (English)

    张雪哲; 王武; 卢延; 黄振国; 洪闻; 尚燕宁; 任安

    2003-01-01

    Objective:To investigate the role of CT scanning in diagnosing severe acute respiratory syndrome(SARS). Methods: One hundred and twelve times of spiral CT scanning, 106 times on the chest with standard pulmonary and mediastinal window, 5 on the brain and once on the abdomen, were performed in 82 patients (37 males and 45 females) of SARS. Results: Bilateral shadows showed in 66 patients (80.48%) and unilateral shadow in 16 (19.52%). The lung CT findings were sub-pleural focal consolidation in 26 patients (31.70%), flaky cloudy opacity in 53 (64.63%), large area consolidation in 9 (10.97%), ground-glass blurry shadow in 31 (37.80%), alveolar substantive shadow in 14 (17.07%) and interstitial changes in 16 (19.51%). The pulmonary CT signs of SARS were relatively characterized by: (1) The lesions tending to multiply occur, mostly to be bilaterally distributed and commonly involved in the lower lung field. (2) The lung shadows mostly showed as sub-pleural focal consolidation, flaky cloudy shadow, large area consolidation, ground-glass blurry shadow, and often accompanied with signs of broncho-inflation. (3) Having opacified nodular shadows in the alveolar cavities. (4) Rapid progressions or changes on the size, amount, and distribution of the lesions likely to be found in dynamic observation of chest X-ray and CT scanning, i.e., markedly dynamic changes found within 24 to 48 hrs. Lesions with these characteristics may be recognized as pulmonary changes possibly induced by SARS. Complications were found in 6 patients (7.31%), including tuberculosis of lung and brain accompanied with pneumomediastinum in one patient, secondary infection of lung in 2, pneumothorax in 1, pulmonary fungus in 1, and pyothorax in 1.Conclusion: CT scanning is a sensitive method for diagnosis of SARS, by which more accurate assessment of the abnormal changes of lung and occurrence of complications in SARS patients can be made.

  9. High-sensitive C-reactive protein is associated with reduced lung function in young adults

    DEFF Research Database (Denmark)

    Rasmussen, F; Mikkelsen, D; Hancox, R J;

    2009-01-01

    Systemic inflammation has been associated with reduced lung function. However, data on the interrelationships between lung function and inflammation are sparse, and it is not clear if low-grade inflammation leads to reduced lung function. Associations between high-sensitive C-reactive protein (CR...

  10. Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation

    NARCIS (Netherlands)

    Hofhuis, W.; Hanekamp, M.N.; Ijsselstijn, H.; Nieuwhof, E.M.; Hop, W.C.J.; Tibboel, D.; Jongste, J.C. de; Merkus, P.J.F.M.

    2011-01-01

    OBJECTIVE: To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenati

  11. 急性百草枯中毒患者百草枯含量、肾及肺功能指标对其预后影响%The Effect of Paraquat Levels,Kidney and Lung Function in Patients with Acute Paraquat Poisoning to Prognosis

    Institute of Scientific and Technical Information of China (English)

    朱文捷

    2014-01-01

    目的:研究急性百草枯中毒患者的百草枯含量、肾功能指标和肺功能指标与其预后关系。方法:选择107例急性百草枯中毒患者为研究对象,根据预后分为存活组和死亡组,检测患者血尿的百草枯含量、肾功能指标和肺功能指标。结果:死亡组患者的血浆百草枯含量、尿液百草枯含量分别为9.54±1.13 mg/和423.23±63.43 mg/L均高于存活组;血肌酐、血尿素氮、二氧化碳分压(PaCO2)分别为141.8±18.2mmol/L、11.4±2.2mmol/L和1.32±6.32mmHg,均高于存活组,氧分压(PaO2)、实际碳酸氢盐(PCO3-)和剩余碱(BE)分别为79.44±10.42mmHg、14.82±2.45mmol/L和(-14.56±3.42) mmol/L,均低于存活组(P<0.05)。结论:百草枯中毒患者的百草枯含量、肺功能和肾功能指标与其预后密切相关,百草枯含量、血肌酐、血尿素氮、PaCO2、剩余碱可提示患者的存活情况。%Objective:To study the relation between paraquat levels , renal function and lung function in patients with acute paraquat poi-soning and its prognosis .Methods:107 patients with acute paraquat poisoning were studied , were divided into survival group and death group according to the prognosis , paraquat levels , renal function and lung function was detected in the patients .Results:Plasma levels, urine paraquat levels was (9.54 ±1.13,423.23 ±63.43) mg/L in the death group, was higher than that in the survival group .Serum creatinine, blood urea nitrogen, carbon dioxide partial pressure (PaCO2) was (141.8 ±18.2)mmol/L,(11.4 ±2.2)mmol/L and(41.32 ±6.32)mmHg,higher than that in the survival group , pressure of oxygen (PaO2),actual bicarbonate (PCO3-) and base excess (BE) was(79.44 ±10.42)mmHg,(14.82 ±2.45)mmol/L and(-14.56 ±3.42) mmol/L,lower than that in the survival group (P<0.05). Conclusion:The content of paraquat , pulmonary and renal function in the patients with paraquat

  12. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    Science.gov (United States)

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

    2016-01-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their As levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the Soluble Receptor for Advanced Glycation Endproducts (sRAGE) sputum level was significantly lower and Matrix Metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsenic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/Tissue Inhibitor of Metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. PMID:26048584

  13. Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline.

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    Giovanni Bacci

    Full Text Available Chronic airway infection is a hallmark feature of cystic fibrosis (CF disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD and patients with a stable lung function (S. The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas. In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF.

  14. Surgical treatment of patients with lung cancer and limited lung function: Preoperative assessment, operative mortality and morbidity

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    Subotić Dragan

    2007-01-01

    Full Text Available Introduction: Lung resection in patients with limited lung function is one of the greatest challenges in general thoracic surgery. Objective. The aim of the study was to analyze the pattern of lung function changes after operation, operative morbidity and mortality and to compare them with control group of patients. Method. The study included 34 patients with limited lung function, operated for primary lung cancer in one-year period. All patients underwent preoperative desobstructive treatment. The type of ventilatory disorder was analyzed depending on preoperative radiographic and bronchoscopic aspect. Statistics: chisquare test, t-test. Results. In patients with lobectomy, the mean difference in forced expiratory volume in the first second (FEV1 between preoperative and postoperative values was 16.81%, whilst in the pneumonectomy group this difference was 39.51%. The mean change in forced vital capacity (FVC in the lobectomy and pneumonectomy group was 15.83% and 42.73% respectively. In the control group of 28 patients with lobectomy, the decrease in FVC and FEV1 was 19.9% and 24.18% respectively. In the control group of 28 patients with pneumonectomy, the decrease in FVC and FEV1 was 43.52% and 41.36% respectively. In patients with limited lung function and lobectomy, changes in FEV1 and VC after resection were significantly lower compared to the control group of patients with lobectomy and normal lung function. None of 34 operated patients with borderline lung function died inside 30 postoperative days. In the same period, of a total number of 344 patients without respiratory function impairment, operative mortality was 3.1%. In the analyzed group, operative morbidity was 32.35%. Cardiovascular and respiratory complications in the analyzed and control groups occurred in 14.7% and 6.1% of patients respectively (p>0.05. Conclusion. Surgery should not be excluded in patients with borderline lung function prior to preoperative treatment and

  15. Leukocyte depletion during CPB: effects on inflammation and lung function.

    Science.gov (United States)

    de Amorim, Célio Gomes; Malbouisson, Luiz Marcelo Sá; da Silva, Francisco Costa; Fiorelli, Alfredo Inácio; Murakami, Caroline Kameio Fernandes; Carmona, Maria José Carvalho

    2014-02-01

    Cardiopulmonary bypass (CPB) is related to inflammatory response and pulmonary dysfunction. The aim of this study was to evaluate the effects of CPB leukocyte filtration on inflammation and lung function after coronary artery bypass grafting (CABG). A prospective randomized study was performed to compare CABG patients undergoing CPB leukocyte filtration (n = 9) or standard CPB (n = 11). Computed tomography, oxygenation, leukocyte count, hemodynamic data, PaO2/FiO2, shunt fraction, interleukins, elastase, and myeloperoxidase were evaluated. Data were analyzed using two-factor ANOVA for repeated measurements. The filtered group showed lower neutrophil counts up to 50 min of CPB, lower shunt fraction up to 6 h after surgery, and lower levels of IL-10 at the end of surgery (p CPB results in neutrophil sequestration by a short time, decreased IL-10 serum levels, and lower worsening of lung function only temporarily.

  16. Lung function and long-term exposure to cement dust

    DEFF Research Database (Denmark)

    Rasmussen, F V; Borchsenius, L; Holstein, B

    1977-01-01

    In a cross-sectional epidemiological survey a selected group of former and present cement factory workers and a random sample of the corresponding urban population underwent dynamic spirometry. Based upon life experience the subjects were grouped into four occupational categories. Three hundred...... and one men were grouped as cement factory workers, 649 were grouped as blue collar workers, 218 as white collar workers and 102 men had predominantly been occupied in farming, forestry and fishing. On the average the investigated men had spent more than 75% of their total occupational life in their main...... throughout life had better ventilatory lung function than any of the other three occupational categories. No significant differences in lung function between cement factory workers and other blue collar workers with comparable smoking habits could be demonstrated by use of the maximal midexpiratory flow...

  17. Changes in Functional Lung Regions During the Course of Radiation Therapy and Their Potential Impact on Lung Dosimetry for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Xue [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan (China); Frey, Kirk [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Matuszak, Martha; Paul, Stanton; Ten Haken, Randall [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Yu, Jinming [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan (China); Kong, Feng-Ming, E-mail: fkong@gru.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiation Oncology, Georgia Regents University, Augusta, Georgia (United States)

    2014-05-01

    Purpose: To study changes in functional activity on ventilation (V)/perfusion (Q) single-photon emission computed tomography (SPECT) during radiation therapy (RT) and explore the impact of such changes on lung dosimetry in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Fifteen NSCLC patients with centrally located tumors were enrolled. All patients were treated with definitive RT dose of ≥60 Gy. V/Q SPECT-CT scans were performed prior to and after delivery of 45 Gy of fractionated RT. SPECT images were used to define temporarily dysfunctional regions of lung caused by tumor or other potentially reversible conditions as B3. The functional lung (FL) was defined on SPECT by 2 separate approaches: FL1, a threshold of 30% of the maximum uptake of the patient's lung; and FL2, FL1 plus B3 region. The impact of changes in FL between initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. Results: Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001). Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10 patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based anatomical lung had significantly lower values in FL1 than FL2, with a median reduction in the volume of lung receiving a dose of at least 20 Gy (V{sub 20}) of 3%, 5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively. Conclusions: Regional ventilation and perfusion function improve significantly during RT in centrally located NSCLC. Lung dosimetry values vary notably between different definitions of functional lung.

  18. Effect of porcine reproductive and respiratory syndrome virus (PRRSV) on alveolar lung macrophage survival and function

    DEFF Research Database (Denmark)

    Oleksiewicz, Martin B.; Nielsen, Jens

    1999-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) recently emerged as an important cause of reproductive disorders and pneumonia in domestic pigs throughout the world. Acute cytocidal replication of PRRSV in alveolar lung macrophages causes the acute pneumonia; however, it remains largely...... infection in this system. In short, in our minimal system containing only a single cell type, phagocytosis-suppressive effects of PRRSV infection were detected, that acted at the culture level by reducing the total number of alveolar lung macrophages....

  19. Protective Effects of Apigenin Against Paraquat-Induced Acute Lung Injury in Mice.

    Science.gov (United States)

    Luan, Rui-Ling; Meng, Xiang-Xi; Jiang, Wei

    2016-04-01

    This study aimed to investigate the protective effects of apigenin against paraquat (PQ)-induced acute lung injury (ALI) in mice. Male Kunming mice were randomly divided into five groups: group 1 (control), group 2 (PQ), group 3 (PQ + apigenin 25 mg/kg), group 4 (PQ + apigenin 50 mg/kg), and group 5 (PQ + apigenin 100 mg/kg). The PQ + apigenin group received apigenin by gavage daily for consecutive 7 days, respectively, while the mice in control and PQ groups were given an equivalent volume of saline. We detected the lung wet/dry weight ratios and the histopathology of the lung. The levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined using enzyme-linked immunosorbent assay (ELISA) kits. The activity of nuclear factor (NF)-κB was also determined. The results indicated that apigenin administration decreased biochemical parameters of inflammation and oxidative stress, and improved oxygenation and lung edema in a dose-dependent manner. These protective effects of apigenin were associated with inhibition of NF-κB. In conclusion, apigenin reduces PQ-induced ALI by inhibition of inflammation and oxidative stress.

  20. Regional pulmonary inflammation in an endotoxemic ovine acute lung injury model.

    Science.gov (United States)

    Fernandez-Bustamante, A; Easley, R B; Fuld, M; Mulreany, D; Chon, D; Lewis, J F; Simon, B A

    2012-08-15

    The regional distribution of inflammation during acute lung injury (ALI) is not well known. In an ovine ALI model we studied regional alveolar inflammation, surfactant composition, and CT-derived regional specific volume change (sVol) and specific compliance (sC). 18 ventilated adult sheep received IV lipopolysaccharide (LPS) until severe ALI was achieved. Blood and bronchoalveolar lavage (BAL) samples from apical and basal lung regions were obtained at baseline and injury time points, for analysis of cytokines (IL-6, IL-1β), BAL protein and surfactant composition. Whole lung CT images were obtained in 4 additional sheep. BAL protein and IL-1β were significantly higher in injured apical vs. basal regions. No significant regional surfactant composition changes were observed. Baseline sVol and sC were lower in apex vs. base; ALI enhanced this cranio-caudal difference, reaching statistical significance only for sC. This study suggests that apical lung regions show greater inflammation than basal ones during IV LPS-induced ALI which may relate to differences in regional mechanical events.

  1. Protective Effect of Isorhamnetin on Lipopolysaccharide-Induced Acute Lung Injury in Mice.

    Science.gov (United States)

    Yang, Bo; Li, Xiao-Ping; Ni, Yun-Feng; Du, Hong-Yin; Wang, Rong; Li, Ming-Jiang; Wang, Wen-Chen; Li, Ming-Ming; Wang, Xu-Hui; Li, Lei; Zhang, Wei-Dong; Jiang, Tao

    2016-02-01

    Isorhamnetin has been reported to have anti-inflammatory, anti-oxidative, and anti-proliferative effects. The aim of this study was to investigate the protective effect of isorhamnetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice by inhibiting the expression of cyclooxygenase-2 (COX-2). The effects of isorhamnetin on LPS-induced lung pathological damage, wet/dry ratios and the total protein level in bronchoalveolar lavage fluid (BALF), inflammatory cytokine release, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, and malondialdehyde (MDA) level were examined. In addition, the COX-2 activation in lung tissues was detected by Western blot. Isorhamnetin pretreatment improved the mice survival rates. Moreover, isorhamnetin pretreatment significantly attenuated edema and the pathological changes in the lung and inhibited protein extravasation in BALF. Isorhamnetin also significantly decreased the levels of inflammatory cytokines in BALF. In addition, isorhamnetin markedly prevented LPS-induced oxidative stress. Furthermore, isorhamnetin pretreatment significantly suppressed LPS-induced activation of COX-2. Isorhamnetin has been demonstrated to protect mice from LPS-induced ALI by inhibiting the expression of COX-2.

  2. Rosiglitazone dampens pulmonary inflammation in a porcine model of acute lung injury.

    Science.gov (United States)

    Mirakaj, Valbona; Mutz, Christian; Vagts, Dierk; Henes, Janek; Haeberle, Helene A; Husung, Susanne; König, Tony; Nöldge-Schomburg, Gabriele; Rosenberger, Peter

    2014-08-01

    The hallmarks of acute lung injury (ALI) are the compromised alveolar-capillary barrier and the extravasation of leukocytes into the alveolar space. Given the fact that the peroxisome proliferator-activated receptor-γ agonist rosiglitazone holds significant anti-inflammatory properties, we aimed to evaluate whether rosiglitazone could dampen these hallmarks of local pulmonary inflammation in a porcine model of lung injury. For this purpose, we used a model of lipopolysaccharide (LPS, 50 μg/kg)-induced ALI. One hundred twenty minutes following the infusion of LPS, we started the exposure to rosiglitazone through inhalation or infusion. We found that intravenous rosiglitazone significantly controlled local pulmonary inflammation as determined through the expression of cytokines within the alveolar compartment. Furthermore, we found a significant reduction of the protein concentration and neutrophil activity within the alveolar space. In summary, we therefore conclude that the treatment with rosiglitazone might dampen local pulmonary inflammation during the initial stages of ALI.

  3. Sesamin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibition of TLR4 Signaling Pathways.

    Science.gov (United States)

    Qiang, Li; Yuan, Jiang; Shouyin, Jiang; Yulin, Li; Libing, Jiang; Jian-An, Wang

    2016-02-01

    Recent studies suggested that TLR4 signaling pathways played an important role in the development of LPS-induced acute lung injury (ALI). Sesamin, a sesame lignan exacted from sesame seeds, has been shown to exhibit significant anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of sesamin on LPS-induced ALI in mice. Mice ALI model was induced by intratracheal instillation of LPS. Sesamin was given 1 h after LPS challenge. Our results showed that sesamin inhibited LPS-induced lung pathological change, edema, and myeloperoxidase (MPO) activity. Sesamin suppressed LPS-induced inflammatory cytokines TNF-α, IL-6, and IL-1β production. Furthermore, sesamin inhibited LPS-induced TLR4 expression and NF-κB activation. In conclusion, the results of this study indicated that sesamin protected against LPS-induced ALI by inhibition of TLR4 signaling pathways.

  4. Protective effect of carvacrol on acute lung injury induced by lipopolysaccharide in mice.

    Science.gov (United States)

    Feng, Xiaosheng; Jia, Aiqing

    2014-08-01

    Carvacrol, the major component of Plectranthus amboinicus, has been known to exhibit anti-inflammatory activities. The aim of this study was to investigate the effects of carvacrol on lipopolysaccharide (LPS)-induced endotoxemia and acute lung injury (ALI) in mice. Mice were injected intraperitoneally (i.p.) with LPS and the mortality of mice for 7 days were observed twice a day. Meanwhile, the protective effect of carvacrol (20, 40 or 80 mg/kg) on LPS-induced endotoxemia were detected. Using an experimental model of LPS-induced ALI, we examined the effect of carvacrol in resolving lung injury. The results showed that carvacrol could improve survival during lethal endotoxemia and attenuate LPS-induced ALI in mice. The anti-inflammatory mechanisms of carvacrol may be due to its ability to inhibit NF-κB and MAPKs signaling pathways, thereby inhibiting inflammatory cytokines TNF-α, IL-6 and IL-1β production.

  5. PLAUR polymorphisms and lung function in UK smokers

    Directory of Open Access Journals (Sweden)

    Connolly Martin J

    2009-10-01

    Full Text Available Abstract Background We have previously identified Urokinase Plasminogen Activator Receptor (PLAUR as an asthma susceptibility gene. In the current study we tested the hypothesis that PLAUR single nucleotide polymorphisms (SNPs determine baseline lung function and contribute to the development of Chronic Obstructive Pulmonary Disease (COPD in smokers. Methods 25 PLAUR SNPs were genotyped in COPD subjects and individuals with smoking history (n = 992. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV1, FEV1/FVC in all smokers. Genotype frequencies were compared in spirometry defined smoking controls (n = 176 versus COPD cases (n = 599 and COPD severity (GOLD stratification using logistic regression. Results Five SNPs showed a significant association (p 1 respectively. rs740587(-22346, rs11668247(-20040 and rs344779(-3666 in the 5'region were associated with increased FEV1/FVC ratio. rs740587 was also protective for COPD susceptibility and rs11668247 was protective for COPD severity although no allele dose relationship was apparent. Interestingly, several of these associations were driven by male smokers not females. Conclusion This study provides tentative evidence that the asthma associated gene PLAUR also influences baseline lung function in smokers. However the case-control analyses do not support the conclusion that PLAUR is a major COPD susceptibility gene in smokers. PLAUR is a key serine protease receptor involved in the generation of plasmin and has been implicated in airway remodelling.

  6. Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model

    Institute of Scientific and Technical Information of China (English)

    Wei-ming YAN; Jia-quan HUANG; Xiao-ping LUO; Qin NING

    2007-01-01

    To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

  7. Identification and examination of a novel 9-bp insert/deletion polymorphism on porcine SFTPA1 exon 2 associated with acute lung injury using an oleic acid-acute lung injury model.

    Science.gov (United States)

    Zhang, Yuebo; Zhang, Longchao; Wang, Ligang; Qiao, Lijuan; Liang, Jing; Yan, Hua; Zhao, Kebin; Liu, Xin; Wang, Lixian

    2015-06-01

    The pulmonary surfactant-associated protein (SFTPA1, SP-A) gene has been studied as a candidate gene for lung disease resistance in humans and livestock. The objective of the present study was to identify polymorphisms of the porcine SFTPA1 gene coding region and its association with acute lung injury (ALI). Through DNA sequencing and the PCR-single-strand conformation polymorphism method, a novel 9-bp nucleotide insertion (+) or deletion (-) was detected on exon 2 of SFTPA1, which causes a change in three amino acids, namely, alanine (Ala), glycine (Gly) and proline (Pro). Individuals of three genotypes (-/-, +/- and +/+) were divided into equal groups from 60 Rongchang pigs that were genotyped. These pigs were selected for participation in the oleic acid (OA)-ALI model by 1-h and 3-h injections of OA, and there were equal numbers of pigs in the control and injection groups. The lung water content, a marker for acute lung injury, was measured in this study; there is a significant correlation between high lung water content and the presence of the 9-bp indel polymorphism (P polymorphism causing altered expression of the gene. The individuals with the -/- genotype showed lower lung water content than the +/+ genotype pigs, which suggests that polymorphism could be a potential marker for lung disease-resistant pig breeding and that pig can be a potential animal model for human lung disease resistance in future studies.

  8. Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Yuben Moodley

    2016-07-01

    Full Text Available Acute lung injury/acute respiratory distress syndrome (ALI/ARDS is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n = 6 to intravenous oleic acid (OA injury, ventilation and hMSC infusion, while the controls (n = 5 had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1 h after the administration of OA. The animals were monitored for additional 4 h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB, a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p = 0.04. There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p = 0.063. There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4 h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term.

  9. The role of the acute phase protein PTX3 in the ventilator-induced lung injury

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    JM Real

    2008-06-01

    Full Text Available The pentraxin 3 (PTX3 is an acute phase proinflammatory protein produced by fibroblasts and alveolar epithelial cells. We have previously demonstrated that PTX3 is a key modulator of inflammation. Mechanical ventilation (MV is a life saving therapeutic approach for patients with acute lung injury that, nevertheless could lead to an inflammatory response and tissue injury (ventilator-induced lung injury: VILI, representing a major cause of iatrogenic lung damage in intensive units. Our objective was to investigate the role of PTX3 in VILI. PTX3 transgenic, knockout and Wt control mice (n = 12/group were ventilated (45ml·kg–1 until respiratory system Elastance increased 50% (Ers150%, an indicator of VILI. Histological analysis demonstrated that using a Ers150% was appropriate for our analysis since identical degrees of inflammation were observed in Tg, KO and Wt mice as assessed by leukocyte infiltration, oedema, alveolar collapse and number of breaks in alveolar septa. However, Tg mice reached Ers150% faster than Wt controls (p = 0.0225. We also showed that the lack of PTX3 does not abolish the occurrence of VILI in KOs. Gene expression profile of PTX3, IL-1beta, IL-6, KC, IFNgamma, TGFbeta and PCIII were investigated by QPCR. MV drastically up modulated PTX3 as well as IL-1beta, IL-6, IFNgamma and KC. Alternatively, mice were ventilated for 20, 40 and 60 min. The faster kinetics of Tg mice to reach Ers150% was accompanied by an earlier augmentation of IL-1b and PTX3 expression. The kinetics of local PTX3 expression in the lungs of ventilated mice strongly suggests the involvement of this pentraxin in the pathogenesis of VILI.

  10. Review: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies

    Institute of Scientific and Technical Information of China (English)

    LUH Shi-ping; CHIANG Chi-huei

    2007-01-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung.Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.

  11. Postmortem changes in lungs in severe closed traumatic brain injury complicated by acute respiratory failure

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-08-01

    Full Text Available V.А. Tumanskіy, S.І. Ternishniy, L.M. Tumanskaya Pathological changes in the lungs were studied in the work of 42 patiens who died from severe closed intracranial injury (SCII. It was complicated with acute respiratory insufficient (ARI. The most modified subpleural areas were selected from every lobe of the lungs for pathological studies. Prepared histological sections were stained by means of hemotoxylin and eosin and by Van Giеson for light microscopy. The results of the investigation have shown absence of the significant difference of pathological changes in the lungs of patients who died from ARI because of severe brain injury and traumatic intracranial hemorrhage. Pathognomic pathological changes in the lungs as a result of acute lung injury syndrome (ALIS were found in deceased patients on the third day since the SCII (n=8. There was a significant bilateral interstitial edema and mild alveolar edema with the presence of red and blood cells in the alveoli, vascular plethora of the septum interalveolar and stasis of blood in the capillaries, the slight pericapillary leukocyte infiltration, subpleural hemorrhage and laminar pulmonary atelectasis. In deceased patients on 4-6 days after SCII that was complicated with ARI (n=14, morphological changes had been detected in the lungs. It was pathognomic for acute respiratory distress syndrome (ARDS with local pneumonic to be layered. A significant interstitial pulmonary edema was observed in the respiratory part of the lungs. The edema has spread from the walls of the alveoli into the interstitial spaces of the bronchioles and blood vessels, and also less marked serous-hemorrhagic alveolar edema with presence of the fibrin in the alveoli and macrophages. The ways of intrapleural lymphatic drainage were dilatated. Histopathological changes in the lungs of those who died on the 7-15th days after severe closed craniocerebral injury with ARI to be complicated (n=12 have been indicative of two

  12. Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome.

    Directory of Open Access Journals (Sweden)

    Xianming Zhang

    Full Text Available It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS, but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS.Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB and abdominal muscle paralysis group (BIPAPAP. All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35-60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment.For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml and oxygenation index (293±36 vs. 226±31 mmHg, lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7 and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9 in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1.Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.

  13. Chronic Exposure to Water-Pipe Smoke Induces Alveolar Enlargement, DNA Damage and Impairment of Lung Function

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    Abderrahim Nemmar

    2016-03-01

    Full Text Available Background/Aim: Epidemiological evidence indicates that water-pipe smoking (WPS adversely affects the respiratory system. However, the mechanisms underlying its effects are not well understood. Recent experimental studies reported the occurrence of lung inflammation and oxidative stress following acute and subacute exposure to WPS. Here, we wanted to verify the extent of inflammation and oxidative stress in mice chronically-exposed to WPS and to evaluate, for the first time, its effect on alveolar injury and DNA damage and their association with impairment of lung function. Methods: Mice were nose-only exposed to mainstream WPS (30 min/day; 5 days/week for 6 consecutive months. Control mice were exposed using the same protocol to atmospheric air only. At the end of the exposure period, several respiratory parameters were assessed. Results: In bronchoalveolar lavage fluid, WPS increased neutrophil and lymphocyte numbers, lactate dehydrogenase, myeloperoxidase and matrix metallopeptidase 9 activities, as well as several proinflammatory cytokines. In lung tissue, lipid peroxidation, reactive oxygen species, superoxide dismutase activity and reduced glutathione were all increased by WPS exposure. Along with oxidative stress, WPS exposure significantly increased lung DNA damage index. Histologically the lungs of WPS-exposed mice had foci of mixed inflammatory cells infiltration in the interalveolar interstitium which consisted of neutrophils, lymphocytes and macrophages. Interestingly, we found dilated alveolar spaces and alveolar ducts with damaged interalveolar septae, and impairment of lung function following WPS exposure. Conclusion: We show the persistence of lung inflammation and oxidative stress in mice chronically-exposed to WPS and demonstrate, for the first time, the occurrence of DNA damage and enlargement of alveolar spaces and ducts associated with impairment of lung function. Our findings provide novel mechanistic elucidation for the

  14. Effects of peroxisome proliferator-activated receptor-β/δ on sepsis induced acute lung injury

    Institute of Scientific and Technical Information of China (English)

    Wang Cairui; Zhou Guopeng; Zeng Zeng

    2014-01-01

    Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the first steps in the development of multiple organ failure induced by sepsis.A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of sepsis.Several studies have suggested a protective role of the peroxisome proliferator activated receptor-β/δ (PPAR-β/δ) in related inflammatory diseases.But the role of PPARβ/δ in ALI remains uncertain.The aim of this study was to investigate the role and possible mechanism of PPARβ/δ in ALI induced by sepsis.Methods Cecal ligation and puncture (CLP) was used as a sepsis model.Rats were randomly divided into four groups,the control group (CON,n=6),sham-operation group (SHAM,n=12),cecal ligation and puncture group (CLP,n=30),GW501516 group (CLP+GW,n=25),which underwent CLP and were subcutaneously injected with the PPAR-β/δ agonist GW501516 (0.05 mg/100 g body weight).Survival was monitored to 24 hours after operation.Blood pressure,serum creatinine,blood urea nitrogen,aspartate aminotrasferase and alanine aminotrasferase were measured after CLP.Concentrations of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β in serum were detected by enzyme linked immunosorbent assay (ELISA) kits.Lung tissue samples were stained with H&E and scored according to the degree of inflammation.Bacterial colonies were counted in the peritoneal fluid.Alveolar macrophages were cultured and incubated with GW501516 (0.15 μmol/L) and PPARβ/δ adenovirus and then treated with Lipopolysaccharide (2 μg/ml) for 2 hours.The TNF-α,IL-1β and IL-6 RNA in lung and alveolar macrophages were determined by real-time PCR.Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in lung and alveolar macrophages was detected by Western blotting.Results GW501516 significantly increased the survival of septic rats,decreased histological damage of the lungs,reduced inflammatory cytokines in serum and

  15. Rituximab treatment in a case of antisynthetase syndrome with severe interstitial lung disease and acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Zappa Maria

    2011-08-01

    Full Text Available Abstract We present a case of severe interstitial pneumonitis, mild polyarthritis and polymyositis, and Raynaud's syndrome with the presence of anti-Jo-1 antibodies, which had been diagnosed as anti-synthetase syndrome. The presence, however, of anti-Ro/SSA antibodies led us to understand that we were dealing here with a more severe form of interstitial lung disease. The patient was treated for acute respiratory failure but he showed resistance to glucocorticoids and cyclosporine. Thus, he was treated with infusions of anti-CD20 therapy (rituximab: his clinical conditions improved very rapidly and a significant decrease in the activity of pulmonary disease was detected using high-resolution computerized tomography (HRCT of the thorax and pulmonary function tests.

  16. Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2017-01-01

    Full Text Available CeO2 nanoparticles (CeO2 NPs which are used as a diesel fuel additive are emitted in the particulate phase in the exhaust, posing a health concern. However, limited information exists regarding the in vivo acute toxicity of CeO2 NPs on multiple organs. Presently, we investigated the acute (24 h effects of intratracheally instilled CeO2 NPs in mice (0.5 mg/kg on oxidative stress, inflammation, and DNA damage in major organs including lung, heart, liver, kidneys, spleen, and brain. Lipid peroxidation measured by malondialdehyde production was increased in the lungs only, and reactive oxygen species were increased in the lung, heart, kidney, and brain. Superoxide dismutase activity was decreased in the lung, liver, and kidney, whereas glutathione increased in lung but it decreased in the kidney. Total nitric oxide was increased in the lung and spleen but it decreased in the heart. Tumour necrosis factor-α increased in all organs studied. Interleukin- (IL- 6 increased in the lung, heart, liver, kidney, and spleen. IL-1β augmented in the lung, heart, kidney, and spleen. Moreover, CeO2 NPs induced DNA damage, assessed by COMET assay, in all organs studied. Collectively, these findings indicate that pulmonary exposure to CeO2 NPs causes oxidative stress, inflammation, and DNA damage in multiple organs.

  17. Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Xuanfei Li

    2014-01-01

    Full Text Available Acute lung injury (ALI is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson’s disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-α, IL-1β, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of IκB and subsequently blocked the activation of nuclear factor (NF-κB induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-κB signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI.

  18. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function.

    Science.gov (United States)

    Kinder, Brent W; Shariat, Cyrus; Collard, Harold R; Koth, Laura L; Wolters, Paul J; Golden, Jeffrey A; Panos, Ralph J; King, Talmadge E

    2010-04-01

    Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a > or = 5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27-53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an "idiopathic" interstitial pneumonia.

  19. Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury

    Institute of Scientific and Technical Information of China (English)

    LIANG Zhi-xin; SUN Ji-ping; WANG Ping; TIAN Qing; YANG Zhen; CHEN Liang-an

    2011-01-01

    Background Acute lung injury (ALI) is a serious and common condition for which there are currently no specific strategies for treatment.Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders.We explored the biological effects of MSCs during endotoxin-induced ALl and the mechanisms involved.Methods MSCs were isolated from male rat bone marrow and the ALl model was induced by intravenous endotoxin injection.Female rats were sacrificed at 6 hours,24 hours,4 days,1 week and 3 weeks post-injection of MSCs or saline and the lung tissue,bronchoalveolar lavage fluid,and serum were harvested for analysis.We further evaluated the survival of the rats and examined the effects of endotoxin-induced injury on the interaction between alveolar macrophages (AMs) and MSCs in ex vivo.Results There was a significant decrease in numbers of neutrophils in bronchoalveolar lavage fluid (P <0.05),and myeloperoxidase activity in the lung (P<0.01),and of TNF-α and IL-1β in serum (P <0.05) in the MSC treated rats at 4 days.Furthermore,MSC treated rats exhibited improved survival,lower lung injury score,higher concentration of IL-10 in the serum and a reduced hydroxyproline content,but these differences were not statistically significant.Moreover,co-cultures of MSCs and AMs had significantly reduced levels of TNF-α,IL-1β and macrophage inflammatory protein (MIP)-1α and significantly increased levels of IL-10 (P<0.05) in the culture supernatants.Conclusions Treatment with intravenous injection of bone marrow-derived MSCs have beneficial effects on endotoxin-induced ALl in rats.The beneficial effect might be achieved through the engraftment of differentiated MSCs in the lungs and appears derive more from their capacity to secrete soluble factors that modulate immune responses.

  20. Visual functional changes during acute elevation of intraocular pressure

    Institute of Scientific and Technical Information of China (English)

    Tian-De SHOU

    2006-01-01

    Glaucoma is closely related to elevation of intraocular pressure (IOP). Many studies have done on the effect of chronic elevation of IOP on the retina and optic nerve, but less attention was paid to the effect of acute elevated IOP. Here we briefly review experimental studies on functional changes of the visual system from the retina to the visual cortex under acute elevated IOP condition, which is similar to that of acute primary angle-closure glaucoma.

  1. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma

    NARCIS (Netherlands)

    McGeachie, Michael J; Yates, Katherine P; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L; Van Natta, Mark L; Wise, Robert A; Szefler, Stanley J; Sharma, Sunita; Kho, Alvin T; Cho, Michael H; Croteau-Chonka, Damien C; Castaldi, Peter J; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A; Zeiger, Robert S; Adkinson, N Franklin; Williams, Paul V; Kelly, H William; Grasemann, Hartmut; Vonk, Judith M; Koppelman, Gerard H; Postma, Dirkje S; Raby, Benjamin A; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L; Tantisira, Kelan G; Silverman, Edwin K; Tonascia, James; Weiss, Scott T; Strunk, Robert C

    2016-01-01

    BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung

  2. Ventilator „Chirana Aura V“ In Two Models Of Neonatal Acute Lung Injury - A Pilot Study

    Directory of Open Access Journals (Sweden)

    Tomclkova L.

    2014-05-01

    Full Text Available In severe respiratory insufficiency, neonatal and pediatric patients should be ventilated artificially by a ventilator. Aim of this experimental study was to evaluate whether the newly developed ventilator Chirana Aura V may effectively ventilate the lungs of animals with two different models of acute lung injury: acute respiratory distress syndrome (ARDS induced by repetitive saline lavage and meconium aspiration syndrome (MAS induced by intratracheal instillation of neonatal meconium. The experiments were performed on 10 adult rabbits (New Zealand white. In ARDS group (n=5, the lungs were repetitively lavaged with saline (30 ml/kg until partial pressure of oxygen (PaO2 in arterial blood was under 26.7 kPa at inspiratory fraction of oxygen FiO2=1.0. In MAS group (n=5, animals were instilled 4 ml/kg of suspension of human meconium (25 mg/ml. When the model of acute lung injury was developed, animals were ventilated for additional 2 hours with pressure control ventilation (PCV regime by ventilator Chirana Aura V. Ventilatory parameters, blood gases, acid-base balance, end-tidal CO2, O2 saturation of hemoglobin, oxygenation indexes, ventilation efficiency index, dynamic lung compliance, and right-to-left pulmonary shunts were measured and calculated in regular time intervals. In both experimental groups, used ventilatory settings provided acceptable gas exchange within the period of observation. Thus, the results indicate that ventilator Chirana Aura V might be suitable for ventilation of animal models of acute lung injury. However, further pre-clinical investigation is needed before its use may be recommended in neonatal and/or pediatric patients with acute lung injury.

  3. Double isotope albuminflux measurement: diagnosis and monitoring of acute lung injury; Doppelisotopen-Albuminfluxmessung: Diagnose und Therapiemonitoring des Acute Lung Injury

    Energy Technology Data Exchange (ETDEWEB)

    Hoegerle, S. [Freiburg Univ. (Germany). Abt. Nuklearmedizin; Braeutigam, P. [Freiburg Univ. (Germany). Abt. Nuklearmedizin; Benzing, A. [Freiburg Univ. (Germany). Anaesthesiologische Klinik; Nitzsche, E. [Freiburg Univ. (Germany). Abt. Nuklearmedizin; Mols, G. [Freiburg Univ. (Germany). Anaesthesiologische Klinik; Geiger, K. [Freiburg Univ. (Germany). Anaesthesiologische Klinik; Moser, E. [Freiburg Univ. (Germany). Abt. Nuklearmedizin

    1997-06-01

    Purpose: Acute Lung Injury (ALI) is a clincial condition which is associated with a high lethality. It is characterized by an increased pulmonary capillary permeability and non-cardiogenic pulmonary edema. This study was designed to answer the question whether double isotope albuminflux measurement is a useful tool both for diagnosis of increased pulmonary capillary permeability and for monitoring therapeutic interventions (nitric oxide (NO) inhalation). Method: In 12 patients with clinical signs of ALI, transvascular albuminflux was measured by a double radioisotope technique before, during and after NO inhalation {sup 99m}Tc labeled albumin and {sup 51}Cr labeled autologous erythrocytes were used as tracer. The radioactivity of both radiopharmaceuticals was measured externally over the right lung by a radiation probe and simultaneously in arterial blood. For quantification of transvascular albuminflux Normalized Index (NI) and Normalized Slope Index (NSI) were calculated. Furthermore, pulmonal vascular pressures and other physiological parameters were recorded. Results: All 12 patients showed markedly increased NSI before inhalation of NO. NSI decreased from 0.0074{+-}0.0046 min{sup -1} without nitric oxide to -0.0051{+-}0.0041 min{sup -1} during nitric oxide and increased to 0.0046{+-}0.0111 min{sup -1} after nitric oxide. The decrease of the NSI correlated well with decrease of venous pulmonary resistance during inhalation of NO. Conclusion: Inhalation of NO reduces transvascular albuminflux in patients with ALI. Double isotope albuminflux measurement enables diagnosis of increased capillary permeability as well as monitoring therapeutic interventions. (orig.) [Deutsch] Ziel: Acute Lung Injury (ALI) ist ein Krankheitsbild mit hoher Letalitaet, das durch eine erhoehte pulmonale Kapillarpermeabilitaet mit einem nichtkardialen Lungenoedem gekennzeichnet ist. In der vorliegenden Studie sollte ueberprueft werden, ob die Doppelisotopen-Albuminfluxmessung sich neben

  4. In vivo microscopy in a porcine model of acute lung injury.

    Science.gov (United States)

    Bickenbach, Johannes; Czaplik, Michael; Dembinski, Rolf; Pelosi, Paolo; Schroeder, Wolfgang; Marx, Gernot; Rossaint, Rolf

    2010-07-31

    Regional inhomogeneity and alveolar mechanics in a porcine model of acute lung injury (ALI) was evaluated using confocal laser scanning microscopy (CLSM). CLSM was performed through thoracic windows of the upper and lower lobes. Image quantification was conducted by use of a volume air index (VAI). Twelve anesthetized, mechanically ventilated pigs were randomized to non-injury (control group, n = 6) or ALI induced by surfactant depletion (ALI group, n = 6). CLSM was performed at baseline, after 1 h at 5 mbar and after 2 h at 15 mbar positive end-expiratory pressure (PEEP). Haemodynamics, respiratory mechanics and calculation of pulmonary ventilation-perfusion distribution by MIGET were determined. At baseline, VAI was not different. In the upper lobes, VAI significantly decreased in ALI compared to control group, with no changes after PEEP application. In the lower lobes, VAI significantly decreased in ALI compared to control group. Incremental PEEP significantly increased VAI in ALI, but not in control group. Haemodynamics were significantly compromised in the ALI group. A significant deterioration in oxygenation and ventilation-perfusion distribution could be seen being restored after PEEP adjustment. The VAI may help to assess regional inhomogeneity of the acutely injured lung.

  5. Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats

    Institute of Scientific and Technical Information of China (English)

    Xi Chen; Shun-Le Li; Tao Wu; Ji-Dong Liu

    2008-01-01

    AIM:To observe the effect of proteasome inhibitor MG-132 on severe acute pancreatitis (SAP) and associated lung injury of rats.METHODS:Male adult SD rats were randomly divided into SAP group,sham-operation group,and MG-132 treatment group.A model of SAP was established by injection of 5% sodium taurocholate into the biliarypancreatic duct of rats.The MG-132 group was pretreated with 10 mg/kg MG-132 intraperitoneally (ip) 30 rnin before the induction of pancreatitis.The changes in serum amylase,myeloperoxidase (MPO) activity of pancreatic and pulmonary tissue were measured.The TNF-α level in pancreatic cytosolic fractions was assayed with an enzyme-linked immunosorbent assay (ELISA) kit.Meanwhile,the pathological changes in both pancreatic and pulmonary tissues were also observed.RESULTS:MG-132 significantly decreased serum amylase,pancreatic weight/body ratio,pancreatic TNF-α level,pancreatic and pulmonary MPO activity (P < 0.05).Histopathological examinations revealed that pancreatic and pulmonary samples from rats pretreated with MG-132 demonstrated milder edema,cellular damage,and inflammatory activity (P < 0.05).CONCLUSION:The proteasome inhibitor MG-132shows a protective effect on severe acute pancreatitis and associated lung injury of rats.

  6. Prediction of residual lung function after lung surgery, and examination of blood perfusion in the pre- and postoperative lung using three-dimensional SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Shimatani, Shinji [Toho Univ., Tokyo (Japan). School of Medicine

    2001-01-01

    In order to predict postoperative pulmonary function after lung surgery, preoperative {sup 99m}Tc-macroaggregated albumin (MAA) lung perfusion scans with single-photon emission computed tomography (SPECT) were performed. Spirometry was also performed before and 4-6 months after surgery in 40 patients. In addition, changes in blood perfusion in the pre- and postoperative lung were examined by postoperative lung perfusion scans in 18 of the 40 patients. We measured the three-dimensional (3-D) imaging volume of the operative and contralateral lungs using the volumes rendering method at blood perfusion thresholds of 20, 50 and 75%, utilizing {sup 99m}Tc-MAA lung perfusion, and predicted pulmonary function by means of the measured volumes. We examined the correlation between predicted and the measured values of postoperative pulmonary function, forced vital capacity (FVC) and forced expiratory volume in one second (FEV{sub 1.0}). The correlation between FEV{sub 1.0} predicted by SPECT (threshold 50%) and measured postoperative lung function resembled that between lung function predicted by the standard planar method and measured FEV{sub 1.0} in the lobectomy group. We then examined the ratios of both pre- and postoperative blood perfusion volumes obtained using 3-D imaging at lung perfusion threshold ranges of 10% each (PV20-29, PV30-39) to pre- and postoperative total perfusion (PV20-100). In the lobectomy group, the postoperative PV20-29/PV20-100 value was significantly higher for the operative side lung than the preoperative PV20-29/PV20-100 value, and the postoperative PV50-59, 60-69, 70-79, 80-89 and 90-100/PV20-100 values were significantly lower than the respective preoperative values. However, in the contralateral lung, the respective pre- and postoperative PV/PV20-100 values were almost identical. These findings suggest that the rate of low blood perfusion increased while the rate of middle to high perfusion decreased in the lobectomy group in the operative

  7. Focused Sonographic Examination of the Heart, Lungs and Deep Veins in Acute Admitted Patients with Respiratory Symptoms

    DEFF Research Database (Denmark)

    Laursen, Christian Borbjerg; Sloth, Erik; Lassen, Annmarie Touborg;

    2012-01-01

    of the clinical examination. In addition, most of the diseases, which are commonly seen in patients with acute respiratory symptoms, can be diagnosed using sonography. Sonography could be integrated as a part of the primary evaluation, potentially improving the diagnostic performance. We therefore evaluated...... the use of sonographic examination of the heart, lungs and deep veins, performed within one hour of the primary evaluation, in acute admitted patients with respiratory symptoms. Methods: We performed a prospective cross sectional blinded observational study, conducted in a medical emergency department....... Patients were included if one or more of the following symptoms or clinical findings were present: respiratory rate > 20, saturation heart, lungs and deep veins...

  8. Effects of SDF-1/CXCR4 on Acute Lung Injury Induced by Cardiopulmonary Bypass.

    Science.gov (United States)

    Shi, Hai; Lu, Rujian; Wang, Shuo; Chen, Honglin; Wang, Fei; Liu, Kun

    2017-03-11

    Acute lung injury (ALI) is one of the most important complications after cardiopulmonary bypass (CPB) and the complex pathophysiology remains to be resolved incomplete. SDF-1/CXCR4 chemokine axis can chemotactically accumulate inflammatory cell to local tissue and regulate the release of inflammatory factors, and SDF-1 has a strong chemotaxis effect on neutrophils with CXCR4. Since CPB animal model was difficult to establish, there was still no report about the effect of SDF-1/CXCR4 on neutrophil chemotaxis in ALI after CPB. Here, a stable CPB rat model was constructed to clarify the role of SDF-1/CXCR4 axis in the CPB-induced ALI. Real-time quantitative PCR (RT-qPCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of SDF-1 and CXCR4 in lung tissues, blood, bronchoalveolar lavage (BALF), and/or isolated neutrophils. SDF-1/CXCR4 was increased after CPB, both of that were increased in blood; CXCR4 was increased in neutrophils; SDF-1/CXCR4 was also increased in BALF of CPB model. Results indicated that SDF-1/CXCR4 axis played a key role in the process of early ALI after CPB, also showed that lung injury was significantly reduce after blocking SDF-1/CXCR4 axis, suggest that CXCR4 might be a new target for ALI treatment.

  9. Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen

    Energy Technology Data Exchange (ETDEWEB)

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Magarelli, J.L.; Bruck, D.C.

    1987-01-01

    We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in /sup 99m/TcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits.

  10. Short-Term Effects of Fine Particulate Matter and Temperature on Lung Function among Healthy College Students in Wuhan, China

    Directory of Open Access Journals (Sweden)

    Yunquan Zhang

    2015-07-01

    Full Text Available Ambient fine particulate matter (PM has been associated with impaired lung function, but the effect of temperature on lung function and the potential interaction effect between PM and temperature remain uncertain. To estimate the short-term effects of PM2.5 combined with temperature on lung function, we measured the daily peak expiratory flow (PEF in a panel of 37 healthy college students in four different seasons. Meanwhile, we also monitored daily concentrations of indoor and outdoor PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm, ambient temperature and relative humidity of the study area, where the study participants lived and attended school. Associations of air pollutants and temperature with lung function were assessed by generalized estimating equations (GEEs. A 10 μg/m3 increase of indoor PM2.5 was associated with a change of −2.09 L/min in evening PEF (95%CI: −3.73 L/min–−0.51 L/min after adjusting for season, height, gender, temperature and relative humidity. The changes of −2.17 L/min (95%CI: −3.81 L/min– −0.52 L/min and −2.18 L/min (95%CI: −3.96 L/min–−0.41 L/min in evening PEF were also observed after adjusting for outdoor SO2 and NO2 measured by Environmental Monitoring Center 3 kilometers away, respectively. An increase in ambient temperature was found to be associated with a decrease in lung function and our results revealed a small but significant antagonistic interactive effect between PM2.5 and temperature. Our findings suggest that ambient PM2.5 has an acute adverse effect on lung function in young healthy adults, and that temperature also plays an important role.

  11. Effect of Radix Paeoniae Rubra on the expression of HO-1 and iNOS in rats with endotoxin-induced acute lung injury

    Institute of Scientific and Technical Information of China (English)

    ZHAN Li-ying; XIA Zhong-yuan; CHEN Chang; WANG Xiao-yuan

    2006-01-01

    Objective: To investigate the effect of Radix Paeoniae Rubra (RPR) on the expression of heme oxygenase ( HO-1 ) and induced nitric oxide synthase (iNOS) in endotoxininduced acute lung injury in rats and its protective mechanism.Methods: Forty Wistar rats were divided randomly into 5 groups with 8 rats in each group: saline control group ( NS group ), lipopolysaccharide group ( LPS group), RPR-treatment group, RPR-prevention group and Herin group. The effect of RPR on protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid,malondialdehyde (MDA) content in the lung and the activity of serum NO were observed. Arterial blood was drawn for blood-gas analysis. The expression of HO-1 and iNOS in lung tissues was detected by immunohistochemitry and morphometry computer image analysis. The histological changes of the lung were observed under light microscope.Results: Compared with that in NS group, the expression of HO-1 and iNOS was markedly increased in LPS group (P < 0.01). In RPR-treatment, RPR-prevention, and Hemin groups, the expression of iNOS was significantly lower, while the expression of HO-1 was higher than that in LPS group (P <0.05). The protein content,the ratio of neutrophiles in bronchoalveolar lavage fluid,the content of MDA and the activity of serum NO in LPS group were significantly higher than those in NS group (P < 0.01 ). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in the LPS group (P<0.01); these parameters of lung injury however, were significantly lower in RPR-treatment, RPR-prevention, and Hemin groups than LPS group (P <0.05or P < 0.01). The pathologic changes of lung tissues were substantially attenuated in RPR-treatment, RPR-prevention, and Hemin groups than LPS group.Conclusions : The high expression of HO-1 reflects an important protective function of the body during lipopolysaccharide-induced acute lung injury. The protective effect of RPR on

  12. Pulmonary Function Testing After Stereotactic Body Radiotherapy to the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Bishawi, Muath [Division of Cardiothoracic Surgery, Stony Brook University Medical Center, Stony Brook, NY (United States); Kim, Bong [Division of Radiology, Stony Brook University Medical Center, Stony Brook, NY (United States); Moore, William H. [Division of Radiation Oncology, Stony Brook University, Stony Brook, NY (United States); Bilfinger, Thomas V., E-mail: Thomas.bilfinger@stonybrook.edu [Division of Cardiothoracic Surgery, Stony Brook University Medical Center, Stony Brook, NY (United States)

    2012-01-01

    Purpose: Surgical resection remains the standard of care for operable early-stage non-small-cell lung cancer (NSCLC). However, some patients are not fit for surgery because of comorbidites such as chronic obstructive pulmonary disease (COPD) and other medical conditions. We aimed to evaluate pulmonary function and tumor volume before and after stereotactic body radiotherapy (SBRT) for patients with and without COPD in early-stage lung cancer. Methods and Materials: A review of prospectively collected data of Stage I and II lung cancers, all treated with SBRT, was performed. The total SBRT treatment was 60 Gy administered in three 20 Gy fractions. The patients were analyzed based on their COPD status, using their pretreatment pulmonary function test cutoffs as established by the American Thoracic Society guidelines (forced expiratory volume [FEV]% {<=}50% predicted, FEV%/forced vital capacity [FVC]% {<=}70%). Changes in tumor volume were also assessed by computed tomography. Results: Of a total of 30 patients with Stage I and II lung cancer, there were 7 patients in the COPD group (4 men, 3 women), and 23 in t he No-COPD group (9 men, 14 women). At a mean follow-up time of 4 months, for the COPD and No-COPD patients, pretreatment and posttreatment FEV% was similar: 39 {+-} 5 vs. 40 {+-} 9 (p = 0.4) and 77 {+-} 0.5 vs. 73 {+-} 24 (p = 0.9), respectively. The diffusing capacity of the lungs for carbon monoxide (DL{sub CO}) did significantly increase for the No-COPD group after SBRT treatment: 60 {+-} 24 vs. 69 {+-} 22 (p = 0.022); however, DL{sub CO} was unchanged for the COPD group: 49 {+-} 13 vs. 50 {+-} 14 (p = 0.8). Although pretreatment tumor volume was comparable for both groups, tumor volume significantly shrank in the No-COPD group from 19 {+-} 24 to 9 {+-} 16 (p < 0.001), and there was a trend in the COPD patients from 12 {+-} 9 to 6 {+-} 5 (p = 0.06). Conclusion: SBRT did not seem to have an effect on FEV{sub 1} and FVC, but it shrank tumor volume and

  13. Bone marrow-derived cells participate in stromal remodeling of the lung following acute bacterial pneumonia in mice.

    Science.gov (United States)

    Serikov, Vladimir B; Mikhaylov, Viatcheslav M; Krasnodembskay, Anna D; Matthay, Michael A

    2008-01-01

    Bone marrow-derived cells (BMDC) have been shown to graft injured tissues, differentiate in specialized cells, and participate in repair. The importance of these processes in acute lung bacterial inflammation and development of fibrosis is unknown. The goal of this study was to investigate the temporal sequence and lineage commitment of BMDC in mouse lungs injured by bacterial pneumonia. We transplanted GFP-tagged BMDC into 5-Gy-irradiated C57BL/6 mice. After 3 months of recovery, mice were subjected to LD(50) intratracheal instillation of live E. coli (controls received saline) which produced pneumonia and subsequent areas of fibrosis. Lungs were investigated by immunohistology for up to 6 months. At the peak of lung inflammation, the predominant influx of BMDC were GFP(+) leukocytes. Postinflammatory foci of lung fibrosis were evident after 1-2 months. The fibrotic foci in lung stroma contained clusters of GFP(+) CD45(+) cells, GFP(+) vimentin-positive cells, and GFP(+) collagen I-positive fibroblasts. GFP(+) endothelial or epithelial cells were not identified. These data suggest that following 5-Gy irradiation and acute bacterial pneumonia, BMDC may temporarily participate in lung postinflammatory repair and stromal remodeling without long-term engraftment as specialized endothelial or epithelial cells.

  14. Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury

    NARCIS (Netherlands)

    A. Hartog (Anneke); G.F. Vazquez de Anda; D.A.M.P.J. Gommers (Diederik); U. Kaisers; S.J.C. Verbrugge (Serge); R. Schnabel; B.F. Lachmann (Burkhard)

    1999-01-01

    textabstractWe have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult r

  15. Atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; ZHANG Yan-bo; LIU Dong-hai; LI Xiao-feng; LIU Ai-jun; FAN Xiang-ming; QIAO Chen-hui

    2013-01-01

    Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis,severe burns,and trauma.It is increasingly recognized that atrial natriuretic peptide (ANP) possesses a broad range of biological activities,including effects on endothelial function and inflammation.A recent study has revealed that ANP exerts anti-inflammatory effects.In this study we tested the effects of human ANP (hANP) on lung injury in a model of oleic acid (OA)-induced acute lung injury (ALl) in rats.Methods Rats were randomly assigned to three groups (n=6 in each group).Rats in the control group received a 0.9% solution of NaCl (1 ml.kg1.h-1) by continuous intravenous infusion,after 30 minutes a 0.9% solution of NaCl (1 ml/kg) was injected intravenously,and then the 0.9% NaCl infusion was restarted.Rats in the ALl group received a 0.9% NaCl solution (1 ml·kg-1·h-1) intravenous infusion,after 30 minutes OA was injected intravenously (0.1 ml/kg),and then the 0.9% NaCl infusion was restarted.Rats in the hANP-treated ALI group received a hANP (0.1μg·kg-1·min-1) infusion,after 30 minutes OA was injected intravenously (0.1 ml/kg),and then the hANP infusion was restarted.The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels.Results Serum intedeukin (IL)-1β,IL-6,IL-10 and tumor necrosis factor (TNF) α were increased in the ALI group at six hours.The levels of all factors were significantly lower in the hANP treated rats (P <0.005).Similarly,levels of IL-1β,IL-6,IL-10 and TNF-α were higher in the lung tissue in the ALI group at six hours.hANP treatment significantly reduced the levels of these factors in the lungs (P <0.005).Histological examination revealed marked reduction in interstitial congestion,edema,and inflammation.Conclusion hANP can attenuate inflammation in an OA-induced lung injury in rat model.

  16. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury.

    Science.gov (United States)

    Hu, Yue; Lou, Jian; Mao, Yuan-Yuan; Lai, Tian-Wen; Liu, Li-Yao; Zhu, Chen; Zhang, Chao; Liu, Juan; Li, Yu-Yan; Zhang, Fan; Li, Wen; Ying, Song-Min; Chen, Zhi-Hua; Shen, Hua-Hao

    2016-12-01

    MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of MTOR or overexpression of autophagy-related proteins significantly attenuated, whereas inhibition of autophagy further augmented, LPS-induced expression of IL6 (interleukin 6) and IL8, through NFKB signaling in HBE cells. Mice with specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly attenuated airway inflammation, barrier disruption, and lung edema, and displayed prolonged survival in response to LPS exposure. Taken together, our results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB. Thus, inhibition of MTOR in pulmonary epithelial cells may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria.

  17. Acute lung injury following inhalation exposure to nerve agent VX in guinea pigs.

    Science.gov (United States)

    Wright, Benjamin S; Rezk, Peter E; Graham, Jacob R; Steele, Keith E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2006-05-01

    A microinstillation technique of inhalation exposure was utilized to assess lung injury following chemical warfare nerve agent VX [methylphosphonothioic acid S-(2-[bis(1-methylethyl)amino]ethyl) O-ethyl ester] exposure in guinea pigs. Animals were anesthetized using Telazol-meditomidine, gently intubated, and VX was aerosolized using a microcatheter placed 2 cm above the bifurcation of the trachea. Different doses (50.4 microg/m3, 70.4 micro g/m(m3), 90.4 microg/m(m3)) of VX were administered at 40 pulses/min for 5 min. Dosing of VX was calculated by the volume of aerosol produced per 200 pulses and diluting the agent accordingly. Although the survival rate of animals exposed to different doses of VX was similar to the controls, nearly a 20% weight reduction was observed in exposed animals. After 24 h of recovery, the animals were euthanized and bronchoalveolar lavage (BAL) was performed with oxygen free saline. BAL was centrifuged and separated into BAL fluid (BALF) and BAL cells (BALC) and analyzed for indication of lung injury. The edema by dry/wet weight ratio of the accessory lobe increased 11% in VX-treated animals. BAL cell number was increased in VX-treated animals compared to controls, independent of dosage. Trypan blue viability assay indicated an increase in BAL cell death in 70.4 microg/m(m3) and 90.4 microg/m(m3) VX-exposed animals. Differential cell counting of BALC indicated a decrease in macrophage/monocytes in VX-exposed animals. The total amount of BAL protein increased gradually with the exposed dose of VX and was highest in animals exposed to 90.4 microg/m(m3), indicating that this dose of VX caused lung injury that persisted at 24 h. In addition, histopathology results also suggest that inhalation exposure to VX induces acute lung injury.

  18. Topical application of phosphatidyl-inositol-3,5-bisphosphate for acute lung injury in neonatal swine

    Science.gov (United States)

    Preuß, Stefanie; Omam, Friede D; Scheiermann, Julia; Stadelmann, Sabrina; Winoto-Morbach, Supandi; von Bismarck, Philipp; Adam-Klages, Sabine; Knerlich-Lukoschus, Friederike; Lex, Dennis; Wesch, Daniela; Held-Feindt, Janka; Uhlig, Stefan; Schütze, Stefan; Krause, Martin F

    2012-01-01

    Hypoxemic respiratory failure of the neonatal organism involves increased acid sphingomyelinase (aSMase) activity and production of ceramide, a second messenger of a pro-inflammatory pathway that promotes increased vascular permeability, surfactant alterations and alveolar epithelial apoptosis. We comparatively assessed the benefits of topical aSMase inhibition by either imipramine (Imi) or phosphatidylinositol-3,5-bisphosphate (PIP2) when administered into the airways together with surfactant (S) for fortification. In this translational study, a triple-hit acute lung injury model was used that entails repeated airway lavage, injurious ventilation and tracheal lipopolysaccharide instillation in newborn piglets subject to mechanical ventilation for 72 hrs. After randomization, we administered an air bolus (control), S, S+Imi, or S+PIP2. Only in the latter two groups we observed significantly improved oxygenation and ventilation, dynamic compliance and pulmonary oedema. S+Imi caused systemic aSMase suppression and ceramide reduction, whereas the S+PIP2 effect remained compartmentalized in the airways because of the molecule's bulky structure. The surfactant surface tensions improved by S+Imi and S+PIP2 interventions, but only to a minor extent by S alone. S+PIP2 inhibited the migration of monocyte-derived macrophages and granulocytes into airways by the reduction of CD14/CD18 expression on cell membranes and the expression of epidermal growth factors (amphiregulin and TGF-β1) and interleukin-6 as pro-fibrotic factors. Finally we observed reduced alveolar epithelial apoptosis, which was most apparent in S+PIP2 lungs. Exogenous surfactant “fortified” by PIP2, a naturally occurring surfactant component, improves lung function by topical suppression of aSMase, providing a potential treatment concept for neonates with hypoxemic respiratory failure. PMID:22882773

  19. Extracorporeal gas exchange in acute lung injury: step by step towards expanded indications?

    Science.gov (United States)

    Dembinski, Rolf; Kuhlen, Ralf

    2010-01-01

    Extracorporeal membrane oxygenation (ECMO) is widely accepted as a rescue therapy in patients with acute life-threatening hypoxemia in the course of severe acute respiratory distress syndrome (ARDS). However, possible side effects and complications are considered to limit beneficial outcome effects. Therefore, widening indications with the aim of reducing ventilator induced lung injury (VILI) is still controversial. Consequently, technological progress is an important strategy. Miniaturized ECMO systems are believed to simplify handling and reduce side effects and complications. Mueller and co-workers evaluated such a small-sized device in 60 patients with severe ARDS. They accomplished both the treatment of severe hypoxemia and reduction of VILI, demonstrating feasibility, a moderate rate of severe complications, and a 45% intensive care survival rate. Although neither randomized nor controlled, this study should encourage others to implement such systems in clinical practice. From a strategic perspective, this is another small but useful step towards implementing extracorporeal gas exchange for the prevention of VILI. It is already common sense that the prevention of acute life-threatening hypoxemia usually outweighs the risks of this technique. The next step should be to prove that prevention of life-threatening VILI balances the risks too.

  20. [Acute respiratory insufficiency due to severe lung injury - ARDS and ALI].

    Science.gov (United States)

    Pfeifer, M

    2010-09-01

    As a consequence of the novel therapeutic option of mechanical ventilation in early intensive care medicine, the acute respiratory distress syndrome (ARDS) was defined as a disease entity of its own representing the most severe form of acute lung injury (ALI). Since its first description four decades ago, our knowledge about the aetiology, physiology, histology and epidemiology of this lethal pulmonary complication of severe acute diseases such as pneumonia or sepsis has been increasing steadily. The initial major therapeutic advances were due to improvements in intensive care medical procedures and monitoring. The large ARDS Network clinical trial on the magnitude of tidal volume impressively demonstrated the feasibility of targeted clinical trials in patients with ARDS that provide robust evidence in this field. This clinical trial, as well as following large-scale trials in ARDS patients, led to significant changes of ventilation therapy and therapeutic strategies that improve the outcome of this disease entity. Advances in the standardisation of care for ARDS patients involving innovative therapeutic procedures such as extracorporeal gas exchange systems will lead to a further improvement in ARDS management and outcome. Modern pulmonary medicine can play a pivotal role in this process and can contribute its rich experiences in all areas of the respiratory system.

  1. Expression and function of secretory type Ⅱ phospholipase A2 in lung of severe acute pancreatitis of rats%重症急性胰腺炎肺组织Ⅱ型分泌型磷脂酶A2的表达及功能改变

    Institute of Scientific and Technical Information of China (English)

    张雪梅; 陈海龙; 王朝晖

    2012-01-01

    [目的]探讨重症急性胰腺炎(SAP)时肺组织Ⅱ型分泌型磷脂酶A2(sPLA2 -Ⅱ)的表达及功能改变.[方法]将SD大鼠随机分为假手术组(SO组,n=10)、模型组(SAP组,n=10).SO组仅行剖腹术,翻动胰腺;SAP组用去氧胆酸钠胰管逆行注射建立SAP合并肺损伤模型.2组动物在术后24 h测pH、PaQ、PaCO2、血淀粉酶、sPLA2 -Ⅱ,肺湿/干比值.应用RT-PCR、western-blot观察肺组织sPLA2-Ⅱ表达,并观察胰、肺组织病理变化.[结果]SAP组血淀粉酶、sPLA2、肺湿/干比值显著高于SO组(P<0.05).SAP组PaO2、pH显著低于SO组(P<0.05),PaCO2、sPLA -Ⅱ显著高于SO组(P<0.05).[结论]AAP时肺组织sPLA2 -Ⅱ表达增高,可能是急性肺损伤的发病机制之一.%[Objective] To investigate the expression of secretory type Ⅱ phospholipase A2 (sPLA2-Ⅱ )in lung in rats with severe acute pancreatitis. [Methods]SD rats were randomly divided into 2 groups of sham operation group(SO,n=10)and SAP model group(SAP,n=10). Severe acute pancreatitis was induced in SAP. Sham operation was only made in SO group. Serum amylase( AMY) levels, Ph, PaO2, PaCO2, sPLA2 and lung wet/dry ratio( W/D) were determined. sPLA2-Ⅱ mRNA expression in lung was detected by RT-PCR. The sPLA2- Ⅱ protein expression in lung was detected by western-blot. The pathologic changes of pancreas and lung were observed 24 hours after establishment of the model. [Results]Serum levels of AMY([7144.19 ±727. 91]U/ L),sPLA2([45.13±6.05]nmol·min-1·ml-1),W/D(8. 57±2.45)and PaCO2([47. 57±2. 55] mmHg)in SAP were remarkably higher than those in SO([1193. 41±192. 54]U/L, [29. 94± 6. 39]nmol·min-1·ml-1 ,[3. 70±0. 90],[27.69±1.02]mmHg,P<0.05). The levels of PaO2 ([79. 24± 5. 84] mmHg)and pH(7. 269±0. 054)in SAP were lower than that in SO([96. 78± 3. 81] mmHg,7. 391±0. 054,P<0. 05). The expression of sPLA2-Ⅱ in lung in SAP was significantly increased than in SO( P<3. 05). The pathologic changes of pancreas and lung in SO

  2. Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

    Directory of Open Access Journals (Sweden)

    Frans J. Walther

    2014-05-01

    Full Text Available Background. Chemical spills are on the rise and inhalation of toxic chemicals may induce chemical acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Although the pathophysiology of ALI/ARDS is well understood, the absence of specific antidotes has limited the effectiveness of therapeutic interventions.Objectives. Surfactant inactivation and formation of free radicals are important pathways in (chemical ALI. We tested the potential of lipid mixtures with advanced surfactant protein B and C (SP-B and C mimics to improve oxygenation and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS.Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS. After establishment of respiratory failure rabbits were treated with a single intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini-B (S-MB, a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture (DPPC:POPC:POPG 5:3:2 by weight, the clinical surfactant Infasurf®, a bovine lung lavage extract with SP-B and C, or synthetic lipids alone. End-points consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry (CBS assays.Results. All three surfactant peptide/lipid mixtures and Infasurf equally lowered the minimum surface tension on CBS, and also improved oxygenation and lung compliance. In both animal models, the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and Infasurf improved lung function further in lavage- than in chemical-induced respiratory failure, with the difference probably due to greater capillary

  3. Expression of TLR4 and CD40 in activated macrophage surface after transfusion-related acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    Guang-Xiu Cai

    2016-01-01

    Objective:To study the expression of TLR4 and CD40 in activated macrophage surface after transfusion-related acute lung injury in rats. Methods:SD rats were selected as experimental animals, lipopolysaccharide and plasma were transfused in turn, animal models with transfusion-related acute lung injury (TRALI) were established, lung tissue was collected to detect wet to dry weight ratio as well as mRNA expression levels of TLR4, NF-κB, CD40, TNF-α, IL-1β, MIP-2 and GRP78, serum was collected to detect TNF-α, IL-1βand MIP-2 contents, and macrophages in peripheral blood were collected to detect mRNA expression levels of TLR4, NF-κB and CD40. Results:Lung tissue wet to dry weight ratio of TRALI group was significantly higher than that of Sham group;mRNA expression levels of TLR4, NF-κB and CD40 in macrophages of TRALI group were significantly higher than those of Sham group;mRNA expression levels of TLR4, NF-κB, CD40, TNF-α, IL-1β, MIP-2 and GRP78 in lung tissue of TRALI group were significantly higher than those of Sham group;serum TNF-α, IL-1βand MIP-2 contents of TRALI group were significantly higher than those of Sham group;SOD and GSH contents in lung tissue of TRALI group were lower than those of Sham group, and contents of MDA and 8-OhdG were higher than those of Sham group. Conclusion:Expression levels of TLR4 and CD40 in activated macrophage surface significantly increase after transfusion-related acute lung injury in rats, which will cause lung injury through inflammatory response, oxidative stress response, endoplasmic reticulum stress and others aspects.

  4. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama; Venosa, Alessandro [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Hall, LeRoy [Drug Safety Sciences, Johnson and Johnson, Raritan, NJ 08869 (United States); Gow, Andrew J. [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sinko, Patrick J. [Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute

  5. Preoperative pulmonary rehabilitation for marginal-function lung cancer patients.

    Science.gov (United States)

    Hashmi, Asra; Baciewicz, Frank A; Soubani, Ayman O; Gadgeel, Shirish M

    2017-01-01

    Background This study aimed to evaluate the impact of preoperative pulmonary rehabilitation in lung cancer patients undergoing pulmonary resection surgery with marginal lung function. Methods Short-term outcomes of 42 patients with forced expiratory volume in 1 s pulmonary rehabilitation) and group B (receiving pulmonary rehabilitation). In group B, a second set of pulmonary function tests was obtained. Results There were no significant differences in terms of sex, age, race, pathologic stage, operative procedure, or smoking years. Mean forced expiratory volume in 1 s and diffusing capacity for carbon monoxide in group A was 1.40 ± 0.22 L and 10.28 ± 2.64 g∙dL(-1) vs. 1.39 ± 0.13 L and 10.75 ± 2.08 g∙dL(-1) in group B. Group B showed significant improvement in forced expiratory volume in 1 s from 1.39 ± 0.13 to 1.55 ± 0.06 L ( p = 0.02). Mean intensive care unit stay was 6 ± 5 days in group A vs. 9 ± 9 days in group B ( p = 0.22). Mean hospital stay was 10 ± 4 days in group A vs. 14 ± 9 days in group B ( p = 0.31). There was no significant difference in morbidity or mortality between groups. Conclusion Preoperative pulmonary rehabilitation can significantly improve forced expiratory volume in 1 s in some marginal patients undergoing lung cancer resection. However, it does not improve length of stay, morbidity, or mortality.

  6. Serum-surfactant SP-D correlates inversely to lung function in cystic fibrosis

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Holmskov, Uffe; Schiøtz, Peter Oluf;

    2010-01-01

    BACKGROUND: Cystic fibrosis (CF) affects the lungs causing infections and inflammation. Surfactant protein D (SP-D) is an innate defense lectin primarily secreted in the lungs. We investigated the influence of the SP-D Met11Thr polymorphism on CF lung function; and serum SP-D as a marker for CF...

  7. Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

    Science.gov (United States)

    Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

    2015-10-01

    Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.

  8. Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yeon Soo [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Chung, Myung Hee [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)]. E-mail: mhchung@catholic.ac.kr; Park, Seog Hee [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Kim, Hyeon-Yeong [Industrial Chemicals Research Center, Industrial Safety and Health Research Institute KISCO, 104-8, Moonji-dong, Yusong-gu, Taejon-si 305-380 (Korea, Republic of); Choi, Byung Gil [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Lim, Hyun Wook [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Kim, Jin Ah [Department of Pathology, Holy Family Hospital, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon-si, Kyung gi-do 420-717 (Korea, Republic of); Yoo, Won Jong [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)

    2007-05-15

    Objectives: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. Methods: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N = 20), 3 days (N = 20), and 28 days (5 days/week) (N = 20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. Results: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p = 0.022) or 6 ppm (p = 0.010), compared with the control. The parenchymal density of the rats exposed to12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48 {+-} 32.82 HU, 3 ppm: -720.65 {+-} 34.21 HU, 6 ppm: -756.41 {+-} 41.68 HU, 12 ppm: -812.56 {+-} 53.48 HU) (p = 0.000). There were significant density differences between each dose in the groups exposed for 28 days (p = 0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow

  9. Structural and functional changes in the minipig lung following irradiation of different lung volumes at a constant mean lung dose; Strukturelle und funktionelle Veraenderungen an der Lunge von Minischweinen nach Bestrahlung unterschiedlich grosser Lungenvolumina mit gleicher mittlerer Lungendosis

    Energy Technology Data Exchange (ETDEWEB)

    Kusche, S.; Herrmann, T.; Appold, S.; Hoelscher, T.; Bruechner, K.; Geyer, P.; Baumann, M.; Kumpf, R.

    2004-07-01

    Minipigs were subjected to irradiation of different lung volumes at approximately the same mean lung dose (D{sub m}ean) and examined for structural and morphological changes of the lung. The outcome confirmed earlier findings on the pig lung. While no significant differences between irradiation groups was found in terms of functional lung changes, there was a clear correlation between functional changes observed and the mean lung dose. This is in good agreement with data from clinical studies. It follows that the mean lung dose is of predictive value in considering functional lung damage in the assessment of different irradiation regimes. By contrast structural damage was found to correlate with applied dose. [German] Es wurden an Minischweinen unterschiedliche grosse Lungenvolumina mit vergleichbaren mittleren Lungendosen (mean lung dose, D{sub mean}) bestrahlt und die funktionellen und morphologischen Veraenderungen bestimmt. Die Untersuchungen zu funktionellen und morphologischen Veaenderungen bestaetigen fruehere Untersuchungen an der Schweinelunge. Hinsichtlich funktioneller Lungenveraenderungen fand sich kein signifikanter Unterschied zwischen den Bestrahlungsarmen, aber es konnte eine eindeutige Korrelation dieser Veraenderungen mit der mittleren Lungendosis D{sub mean} nachgewiesen werden. Dies steht in gutem Einklang mit Daten aus klinischen Untersuchungen. Somit bestaetigt sich, dass die mean lung dose eine praediktive Bedeutung zur Abschaetzung funktionaler Schaeden der Lunge bei der Beurteilung unterschiedlicher Bestrahlungsplaene hat. Die strukturellen Schaeden korrelieren hingegen mit der applizierten Dosis. (orig.)

  10. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation

    Directory of Open Access Journals (Sweden)

    Alexander Moeller

    2015-06-01

    Full Text Available This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases.

  11. Choline Transporters in Human Lung Adenocarcinoma: Expression and Functional Implications

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Choline is an essential nutrient for cell survival and proliferation, however, the expression and function of choline transporters have not been well identified in cancer. In this study, we detected the mRNA and protein expression of organic cation transporter OCT3, carnitine/cation transporters OCTN 1 and OCTN2,and choline transporter-like protein CTL1 in human lung adenocarcinoma cell lines A549, H1299 and SPC-A-1.Their expression pattern was further confirmed in 25 human primary adenocarcinoma tissues. The choline uptake in these cell lines was significantly blocked by CTL1 inhibitor, but only partially inhibited by OCT or OCTN inhibitors. The efficacy of these inhibitors on cell proliferation is closely correlated with their abilities to block choline transport. Under the native expression of these transporters, the total choline uptake was notably blocked by specific PI3K/AKT inhibitors. These results describe the expression of choline transporters and their relevant function in cell proliferation of human lung adenocarcinoma, thus providing a potential"choline-starvation" strategy of cancer interference through targeting choline transporters, especially CTL1.

  12. Pulmonary physiology: future directions for lung function testing in COPD.

    Science.gov (United States)

    Brusasco, Vito; Barisione, Giovanni; Crimi, Emanuele

    2015-02-01

    Chronic obstructive pulmonary disease (COPD) is a term that encompasses different pathological conditions having excessive airflow limitation in common. A wide body of knowledge has been accumulated over the last century explaining the mechanisms by which airway (chronic bronchitis) and parenchymal (emphysema) diseases lead to an indistinguishable spirometric abnormality. Although the definition of emphysema is anatomical, early studies showed that its presence can be inferred with good approximation from measurements of lung mechanics and gas exchange, in addition to simple spirometry. Studies using tests of ventilation distribution showed that abnormalities are present in smokers with normal spirometry, although these tests were not predictive of development of COPD. At the beginning of the third millennium, new documents and guidelines for diagnosis and treatment of COPD were developed, in which the functional diagnosis of COPD was restricted, for the sake of simplicity, to simple spirometry. In recent years, there has been a resurgence of interest in separating bronchitic from emphysematous phenotype of COPD. For this purpose, high-resolution computed tomography scanning has been added to diagnostic work-up. At the same time, methods for lung function testing have been refined and seem promising for detection of early small airways abnormalities. Among them are the forced oscillation technique and the nitrogen phase III slope analysis of the multiple-breath washout test, which may provide information on ventilation inhomogeneity. Moreover, the combined assessment of diffusing capacity for nitric oxide and carbon monoxide may be more sensitive than the latter alone for partitioning diffusive components at parenchymal level.

  13. Socioeconomic status, lung function and admission to hospital for COPD

    DEFF Research Database (Denmark)

    Prescott, E; Lange, P; Vestbo, J

    1999-01-01

    This study analysed the effect of education and income on development of chronic obstructive pulmonary disease (COPD) assessing lung function and hospital admission. The study population consisted of 14,223 subjects, aged 20-90 yrs, randomly sampled from the population of Copenhagen in 1976...... and duration of smoking and inhalation, the difference was 220+/-31 mL and 363+/-39 mL in females and males, respectively. Results for FVC were of the same magnitude. Using a socioeconomic index which combined information on education and household income the association with lung function did not differ...... index in females were 0.74 (0.55-1.02) and 0.27 (0.10-0.73), respectively. Corresponding relative risks in males were 0.47 (0.36-0.63) and 0.35 (0.17-0.70). The results indicate that socioeconomic factors operating from early in life affect the adult risk of developing chronic obstructive pulmonary...

  14. Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice.

    Science.gov (United States)

    Viby, Niels-Erik; Isidor, Marie S; Buggeskov, Katrine B; Poulsen, Steen S; Hansen, Jacob B; Kissow, Hannelouise

    2013-12-01

    The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP-1 displays antiinflammatory and surfactant-releasing effects. Thus, we hypothesize that treatment with GLP-1 analogs will improve pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with a measurement of enhanced pause in a whole-body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Enhanced pause increased dramatically at day 17 in all control mice, but the increase was significantly less in the groups of GLP-1R agonist-treated mice (P agonist-treated mice (P agonist treatment. These results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive pulmonary disease, by decreasing the severity of acute exacerbations. The mechanism of action does not seem to be the modulation of inflammation and SFTP expression.

  15. Relationship of lung function to radiographic reading (ILO) in patients with asbestos related lung disease.

    Science.gov (United States)

    Cotes, J E; King, B

    1988-10-01

    The 1980 International Labour Office (ILO) classification of posteroanterior chest radiographs was used to obtain the scores for profusion of small opacities and pleural abnormalities of 172 men with confirmed or suspected disease of the lungs due to asbestos. After allowance had been made for age, stature, and smoking habit the quantitative score for area of diffuse pleural thickening seen in profile on both lateral chest walls contributed to reductions in inspiratory capacity, expiratory reserve volume, and forced expiratory flow rates. Occlusion of one or both costophrenic angles in the presence of diffuse thickening was associated with further reduction in inspiratory capacity. Profusion of small opacities was associated with a reduction in transfer factor. Diffuse pleural thickening and occlusion of costophrenic angles were associated with relatively low values for the forced expiratory flow rates (MEF50FVC) and FEV1/FVC, whereas small opacities were associated with relatively high values. Thus overall increased, normal, or reduced values of MEF50FVC and FEV1/FVC might occur, depending on the distribution of the radiographic abnormalities. The findings contribute to the validation of the ILO pleural scores; those for diffuse pleural thickening and occlusion of costophrenic angles should be used jointly with the scores for profusion of parenchymal small opacities in interpreting the lung function of persons exposed to asbestos.

  16. Intensive insulin treatment attenuates burn-initiated acute lung injury in rats: role of the protective endothelium.

    Science.gov (United States)

    Zhang, Wan-Fu; Zhu, Xiong-Xiang; Hu, Da-Hai; Xu, Cheng-Feng; Wang, Yun-Chuan; Lv, Gen-Fa

    2011-01-01

    Nonmetabolic effects of intensive insulin therapy in critically ill patients have been reported, but the underlying mechanisms are unclear. This study was designed to test the hypothesis that intensive insulin treatment would attenuate burn-induced acute lung injury by protecting the pulmonary microvascular endothelium. The rat model of burn injury was achieved by exposure to 92°C water for 18 seconds. The rats were randomly allocated into the sham, burn/normal saline (NS), and burn/intensive insulin treatment groups. Blood glucose level was maintained between 5 and 7 mmol/L in rats in the burn/intensive insulin treatment group. Pulmonary injury was assessed by hematoxylin and eosin staining, scanning electron microscopy, bronchoalveolar lavage fluid protein concentrations, the lung wet:dry weight ratio, and lung myeloperoxidase activity. Pulmonary microvascular endothelial cells were examined by transmission electron microscopy. Western blotting was used to determine the protein expression of caspase-3. Intensive insulin treatment markedly attenuated the acute lung injury, revealed by improvements in histological features and significant decreases in bronchoalveolar lavage fluid protein concentrations, pulmonary wet:dry weight ratio, and myeloperoxidase activity at 12 hours after injury (P insulin treatment group when compared with the burn/NS group. Overall, intensive insulin treatment efficiently attenuated pulmonary microvascular endothelial cell dysfunction, decreased cell apoptosis, and inhibited acute lung injury after a burn. These findings may be useful in preventing organ failure after burn injury.

  17. IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A(H1N1)Virus

    Institute of Scientific and Technical Information of China (English)

    Chenggang Li; Chen Wang; Zhongwei Chen; Li Xing; Chong Tang; Xiangwu Ju; Feng Guo; Jiejie Deng; Yan Zhao; Peng Yang; Jun Tang; Penghui Yang; Huanling Wang; Zhongpeng Zhao; Zhinan Yin; Bin Cao; Xiliang Wang; Chengyu Jiang; Yang Sun; Taisheng Li; Chen Wang; Zhong Wang; Zhen Zou; Yiwu Yan; Wei Wang

    2012-01-01

    The 2009 flu pandemic involved the emergence of a new strain of a swine-origin H1N1 influenza virus(S-OIV H1N1)that infected almost every country in the world.Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury.In this report,we are the first to describe a mouse model of S-OIV virus infection with acute lung injury and immune responses that reflect human clinical disease.The clinical efficacy of the antiviral oseltamivir(Tamiflu)administered in the early stages of S-OIV H1N1 infection was confirmed in the mouse model.Moreover,elevated levels of IL-17,Th-17 mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing.IL-17 deficiency or treatment with monoclonal antibodies against IL-17-ameliorated acute lung injury induced by the S-OIV H1N1 virus in mice.These results suggest that IL-17 plays an important role in S-OIV-induced acute lung injury and that monoclonal antibodies against IL-17 could be useful as a potential therapeutic remedy for future S-OIV H1N1 pandemics.

  18. Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

    Science.gov (United States)

    Lunt, Alan; McGhee, Emily; Robinson, Polly; Rees, David; Height, Susan; Greenough, Anne

    2016-02-01

    Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (pvolume from 39.7 to 64.1 ml/m2 (pvolume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children.

  19. Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Aanaes, Kasper; Høiby, Niels;

    2016-01-01

    BACKGROUND: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. METHODS: We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway...... patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. CONCLUSION: We demonstrated...

  20. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury.

    Science.gov (United States)

    Imai, Yumiko; Kuba, Keiji; Neely, G Greg; Yaghubian-Malhami, Rubina; Perkmann, Thomas; van Loo, Geert; Ermolaeva, Maria; Veldhuizen, Ruud; Leung, Y H Connie; Wang, Hongliang; Liu, Haolin; Sun, Yang; Pasparakis, Manolis; Kopf, Manfred; Mech, Christin; Bavari, Sina; Peiris, J S Malik; Slutsky, Arthur S; Akira, Shizuo; Hultqvist, Malin; Holmdahl, Rikard; Nicholls, John; Jiang, Chengyu; Binder, Christoph J; Penninger, Josef M

    2008-04-18

    Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.

  1. Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Nozomi Yabuuchi

    2016-12-01

    Full Text Available High mortality of acute kidney injury (AKI is associated with acute lung injury (ALI, which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS, in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5, in bilateral nephrectomy (BNx-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr, blood urea nitrogen (BUN and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk.

  2. Prediction of postoperative loss of lung function in patients with malignant lung mass. Quantitative regional ventilation-perfusion scanning

    Energy Technology Data Exchange (ETDEWEB)

    Ryo, U.Y. (Univ. of Kentucky College of Medicine, Lexington (USA))

    1990-05-01

    The quantitative measurement of regional ventilation and perfusion distribution is simply and reliably accomplished by using routinely available radioactive gas and perfusion lung scanning agents, and a large field-of-view gamma camera with an on-line computer. The preoperative prediction of postsurgical loss in lung function can be made accurately by using the quantitative ventilation-perfusion lung scan technique. Either a regional ventilation study or perfusion study may be used for the prediction, but analysis of regional ventilation distribution appears to be a better parameter than that of perfusion distribution for the prediction of postoperative loss of FEV1. In the rare case of a patient with a marked ventilation-perfusion deficit, quantitative distribution of both ventilation and perfusion may be needed for an accurate assessment of postsurgical lung function. 18 references.

  3. Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids.

    Science.gov (United States)

    Yamaguchi, K; Mori, M; Kawai, A; Asano, K; Takasugi, T; Umeda, A; Yokoyama, T

    1992-01-01

    To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a

  4. Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis

    Institute of Scientific and Technical Information of China (English)

    Hui-jie MA; Xin-li HUANG; Yan LIU; Ya-min FAN

    2012-01-01

    Aim:We speculated that the enhanced apoptosis of polymorphonuclear neutrophil (PMN) might be responsible for the inhibition of PMN infiltration in the lung.This study was designed to investigate the effects of sulfur dioxide (SO2) on PMN apoptosis in vivo and in vitro,which may mediate the protective action of SO2 on pulmonary diseases.Methods:Acute lung injury (ALI) was induced by intratracheally instillation of lipopolysaccharide (LPS,100 μg/100 g.in 200 μL saline) in adult male SD rats.SO2 solution (25 μmol/kg) was administered intraperitoneally 30 min before LPS treatment.The rats were killed 6 h after LPS treatment.Lung tissues were collected for histopathologic study and SO2 concentration assay.Bronchoalveolar lavage fluid (BALF) was collected for the measurement of PMN apoptosis.For in vitro experiments,rat peripheral blood PMNs were cultured and treated with LPS (30 mg/L) and S02 (10,20 and 30 μmol/L) for 6 h,and apoptosis-related protein expression was detected by Western blotting,and apoptosis rate was measured with flow cytometry.Results:LPS treatment significantly reduced the SO2 concentrations in the lung tissue and peripheral blood,as compared with the control group.Pretreatment with SO2 prevented LPS-induced reduction of the SO2 concentration in the lung tissue and peripheral blood.LPS treatment significantly reduced PMN apoptosis both in vivo and in vitro,which could be prevented by the pretreatment with SO2.The protein levels of caspase-3 and Bax was significantly increased,but Bcl-2 was decreased by the pretreatment with SO2,as compared with LPS administration alone.Conclusion:SO2 plays an important role as the modulator of PMN apoptosis during LPS-induced ALl,which might be one of the mechanisms underlying the protective action of SO2 on pulmonary diseases.

  5. Radioisotope albumin flux measurement of microvascular lung permeability: an independent parameter in acute respiratory failure?

    Energy Technology Data Exchange (ETDEWEB)

    Hoegerle, S.; Nitzsche, E.U.; Reinhardt, M.J.; Moser, E. [Freiburg Univ. (Germany). Div. of Nuclear Medicine; Benzing, A.; Geiger, K. [Freiburg Univ. (Germany). Dept. of Anesthesiology; Schulte Moenting, J. [Freiburg Univ. (Germany). Dept. of Medical Biometry and Statistics

    2001-04-01

    Aim: To evaluate the extent to which single measurements of microvascular lung permeability may be relevant as an additional parameter in a heterogenous clinical patient collective with Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). Methods: In 36 patients with pneumonia (13), non pneumogenic sepsis (9) or trauma (14) meeting the consensus conference criteria of ALI or ARDS double-isotope protein flux measurements ({sup 51}Cr erythrocytes as intravascular tracer, Tc-99m human albumin as diffusible tracer) of microvascular lung permeability were performed using the Normalized Slope Index (NSI). The examination was to determine whether there is a relationship between the clinical diagnosis of ALI/ARDS, impaired permeability and clinical parameters, that is the underlying disease, oxygenation, duration of mechanical ventilation and mean pulmonary-artery pressure (PAP). Results: At the time of study, 25 patients presented with increased permeability (NSI > 1 x 10{sup -3} min{sup -1}) indicating an exudative stage of disease, and 11 patients with normal permeability. The permeability impairment correlated with the underlying disease (p > 0.05). With respect to survival, there was a negative correlation to PAP (p < 0.01). Apart from that no correlations between the individual parameters were found. Especially no correlation was found between permeability impairment and oxygenation, duration of disease of PAP. Conclusion: In ALI and ARDS, pulmonary capillary permeability is a diagnostic parameter which is independent from clinical variables. Permeability measurement makes a stage classification (exudative versus non exudative phase) of ALI/ARDS possible based on a measurable pathophysiological correlate. (orig.) [German] Ziel: Es sollte evaluiert werden, inwieweit Einzelmessungen der mikrovaskulaeren Lungenpermeabilitaet als zusaetzlicher Parameter bei einem heterogenen klinischen Patientenkollektiv mit Acute Lung Injury (ALI) und akuten

  6. Airway hyperresponsiveness and development of lung function in adolescence and adulthood

    DEFF Research Database (Denmark)

    Harmsen, Lotte; Ulrik, Charlotte Suppli; Porsbjerg, Celeste;

    2014-01-01

    Long-term longitudinal studies of lung function from childhood to adulthood are important in linking our understanding of childhood risk factors to adult disease. Airway hyperresponsiveness has been shown to independently affect lung function growth in studies of adolescence. The objective...... of the study was to test the hypothesis that airway hyperresponsiveness has an independent deleterious effect on lung function in adolescence that extends into adulthood....

  7. Neonates with reduced neonatal lung function have systemic low-grade inflammation

    OpenAIRE

    Chawes, Bo L.K.; Stokholm, Jakob; Bønnelykke, Klaus; Pedersen, Susanne Brix; Bisgaard, Hans Flinker

    2015-01-01

    Background: Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced lung function. ObjectiveWe sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation. Methods: Plasma levels of high-sensitivity C-reactive p...

  8. Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

    Directory of Open Access Journals (Sweden)

    Dongdong Liu

    2014-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

  9. Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Olivia Meira Dias

    2014-01-01

    Full Text Available The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs. There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.

  10. Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia

    Science.gov (United States)

    Kraft, Bryan D.; Hess, Dean R.; Harris, R. Scott; Wolf, Monroe A.; Suliman, Hagir B.; Roggli, Victor L.; Davies, John D.; Winkler, Tilo; Stenzler, Alex; Baron, Rebecca M.; Thompson, B. Taylor; Choi, Augustine M.; Welty-Wolf, Karen E.; Piantadosi, Claude A.

    2015-01-01

    Inhaled carbon monoxide (CO) gas has therapeutic potential for patients with acute respiratory distress syndrome if a safe, evidence-based dosing strategy and a ventilator-compatible CO delivery system can be developed. In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI). Animals were inoculated with S. pneumoniae (108-109 CFU) (n = 14) or saline vehicle (n = 5); in a subset with pneumonia (n = 5), we administered low-dose, inhaled CO gas (100–300 ppm × 60–90 min) at 0, 6, 24, and/or 48 h postinoculation and serially measured blood carboxyhemoglobin (COHb) levels. We found that CO inhalation at 200 ppm for 60 min is well tolerated and achieves a COHb of 6–8% with ambient CO levels ≤ 1 ppm. The COHb level measured at 20 min predicted the 60-min COHb level by the Coburn-Forster-Kane equation with high accuracy. Animals given inhaled CO + antibiotics displayed significantly less ALI at 8 days postinoculation compared with antibiotics alone. Inhaled CO was associated with activation of mitochondrial biogenesis in the lung and with augmentation of renal antioxidative programs. These data support the feasibility of safely delivering inhaled CO gas during mechanical ventilation and provide preliminary evidence that CO may accelerate the resolution of ALI in a clinically relevant nonhuman primate pneumonia model. PMID:26320156

  11. Acute ozone-induced differential gene expression profiles in rat lung.

    Science.gov (United States)

    Nadadur, Srikanth S; Costa, Daniel L; Slade, Ralph; Silbjoris, Robert; Hatch, Gary E

    2005-12-01

    Ozone is an oxidant gas that can directly induce lung injury. Knowledge of the initial molecular events of the acute O3 response would be useful in developing biomarkers of exposure or response. Toward this goal, we exposed rats to toxic concentrations of O3 (2 and 5 ppm) for 2 hr and the molecular changes were assessed in lung tissue 2 hr postexposure using a rat cDNA expression array containing 588 characterized genes. Gene array analysis indicated differential expression in almost equal numbers of genes for the two exposure groups: 62 at 2 ppm and 57 at 5 ppm. Most of these genes were common to both exposure groups, suggesting common roles in the initial toxicity response. However, we also identified the induction of nine genes specific to 2-ppm (thyroid hormone-beta receptor c-erb-A-beta; and glutathione reductase) or 5-ppm exposure groups (c-jun, induced nitric oxide synthase, macrophage inflammatory protein-2, and heat shock protein 27). Injury markers in bronchoalveolar lavage fluid (BALF) were used to assess immediate toxicity and inflammation in rats similarly exposed. At 2 ppm, injury was marked by significant increases in BALF total protein, N-acetylglucosaminidase, and lavageable ciliated cells. Because infiltration of neutrophils was observed only at the higher 5 ppm concentration, the distinctive genes suggested a potential amplification role for inflammation in the gene profile. Although the specific gene interactions remain unclear, this is the first report indicating a dose-dependent direct and immediate induction of gene expression that may be separate from those genes involved in inflammation after acute O3 exposure.

  12. Changes in liquid clearance of alveolar epithelium after oleic acid-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    陶军; 杨天德; 陈祥瑞; 黄河

    2004-01-01

    Objective:Impaired active fluid transport of alveolar epithelium may involve in the pathogenesis and resolution of alveolar edema. Thc objective of this study was to explore the changes in alveolar epithelial liquid clearance during lung edema following acute lung injury induced by oleic acid. Methods:Forty-eight Wistar rats were randomly divided into six groups, I.e. , injured, amiloride, ouabain, amiloride plus ouabain and terbutaline groups. Twenty- four hours after the induction of acute lung injury by intravenous oleic acid (0.25 ml/kg), 5% albumin solution with 1.5 μCi 125Ⅰ-labeled albumin (5 ml/kg) was delivered into both lungs via trachea. Alveolar liquid clearance (ALC), extravascular lung water ( EVLW ) content and arterial blood gases were measured one hour thereafter.Results: At 24 h after the infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with EVLW increased by 47.9% and ALC decreased by 49.2%. Addition of either 2 × 10-3 M amiloride or 5 × 10-4 M ouabain to the instillation further reduced ALC and increased EVLW. ALC increased by approximately 63.7% and EVLW decreased by 46.9% with improved hypoxemia in the Terbutaline (10-4 M) group, compared those in injured rats. A significant negative correlation was found between the increment of EVLW and the reduction of ALC. Onclusions:Active fluid transport of alveolar epithelium might play a role in the pathogenesis of lung edema in acute lung injury.

  13. Gravity effects on regional lung ventilation determined by functional EIT during parabolic flights.

    Science.gov (United States)

    Frerichs, I; Dudykevych, T; Hinz, J; Bodenstein, M; Hahn, G; Hellige, G

    2001-07-01

    Gravity-dependent changes of regional lung function were studied during normogravity, hypergravity, and microgravity induced by parabolic flights. Seven healthy subjects were followed in the right lateral and supine postures during tidal breathing, forced vital capacity, and slow expiratory vital capacity maneuvers. Regional 1) lung ventilation, 2) lung volumes, and 3) lung emptying behavior were studied in a transverse thoracic plane by functional electrical impedance tomography (EIT). The results showed gravity-dependent changes of regional lung ventilation parameters. A significant effect of gravity on regional functional residual capacity with a rapid lung volume redistribution during the gravity transition phases was established. The most homogeneous functional residual capacity distribution was found at microgravity. During vital capacity and forced vital capacity in the right lateral posture, the decrease in lung volume on expiration was larger in the right lung region at all gravity phases. During tidal breathing, the differences in ventilation magnitudes between the right and left lung regions were not significant in either posture or gravity phase. A significant nonlinearity of lung emptying was determined at normogravity and hypergravity. The pattern of lung emptying was homogeneous during microgravity.

  14. Rabdosia japonica var. glaucocalyx Flavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Chun-jun Chu

    2014-01-01

    Full Text Available Rabdosia japonica var. glaucocalyx (Maxim. Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim. Hara (RJFs in acute lung injury (ALI mice induced by lipopolysaccharide (LPS. Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3 in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF-α, IL-6, and IL-1β, and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO activity and nitric oxide (NO and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.

  15. A case of lung cancer associated with acute respiratory distress syndrome after thoracic radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Enoki, Masafumi; Tojima, Hirokazu [Tokyo Rosai Hospital (Japan)

    1996-12-01

    A 73-year-old man presented with dyspnea, cough, fever, appetite loss and stridor due to bronchial stenosis. Fiber-optic bronchoscopy revealed an endobronchial lesion in the right main bronchus and biopsy specimens showed poorly differentiated squamous cell carcinoma. The clinical stage of lung cancer was IIIB (T4N2M0). The patient received 60 Gy in 30 fractions over 43 days to a field including the right hilum and mediastinum. The tumor decreased in size and stenosis of the bronchus disappeared. A week after completion of radiation the patient began to have high grade fever and dyspnea, and progressive hypoxia developed. A chest radiograph showed diffuse bilateral interstitial infiltrates. Despite mechanical ventilation with PEEP and the administration of steroids, he died of respiratory failure three weeks after completion of radiation. Necropsy specimens obtained from the left lung revealed massive deposition of fibrin in the alveolar airspaces associated with hyaline membranes and hyperplasia of type II cells indicating diffuse alveolar damage. The patient had mild pulmonary fibrosis on a CT scan taken before the start of radiotherapy. We conclude that care should be taken if the case has pulmonary fibrosis because radiation therapy can precipitate severe radiation pneumonitis and acute respiratory distress syndrome in such cases. (author)

  16. Acute lung injury induced by H9N2 virus in mice

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Shan Yunfeng; Chi Ying; Wen Tian; Han Xiaodong

    2014-01-01

    Background H9N2 avian influenza viruses (AIVs) have repeatedly caused infections in mammals even humans in many countries.The purpose of our study was to evaluate the acute lung injury (ALI) caused by H9N2 viral infection in mice.Methods Six-to eight-week-old female SPF C57BL/6 mice were infected intranasally with 1x104 MID50 of A/HONG KONG/2108/2003 [H9N2 (HK)] virus.Clinical signs,pathological changes,virus titration in tissues of mice,arterial blood gas,and cytokines in bronchoalveolar lavage fluid (BALF) and serum were observed at different time points after AIV infection.Results H9N2-AIV-infected mice exhibited severe respiratory syndrome,with a mortality rate of 50%.Lung histopathological changes in infected mice included diffuse pneumonia,alveolar damage,inflammatory cellular infiltration,interstitial and alveolar edema,and hemorrhage.In addition,H9N2 viral infection resulted in severe progressive hypoxemia,lymphopenia,and a significant increase in interleukin 1,interleukin 6,tumor necrosis factor,and interferon in BALF and serum.Conclusions The results suggest that H9N2 viral infection induces a typical ALl in mice that resembles the common features of ALl.Our data may facilitate the future studies of potential avian H9N2 disease in humans.

  17. Galantamine protects against lipopolysaccharide-induced acute lung injury in rats

    Directory of Open Access Journals (Sweden)

    G. Li

    2016-01-01

    Full Text Available Lipopolysaccharide (LPS-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI. The high mobility group box 1 (HMGB1 protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS, and LPS+GAL group (5 mg/kg GAL before LPS administration. Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D weight ratio, myeloperoxidase (MPO activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline, 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA. Moreover, GAL treatment significantly decreased the mortality rate (ANOVA. In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.

  18. Forced expiratory flows' contribution to lung function interpretation in schoolchildren.

    Science.gov (United States)

    Boutin, Bernard; Koskas, Marc; Guillo, Houda; Maingot, Lucia; La Rocca, Marie-Claude; Boulé, Michèle; Just, Jocelyne; Momas, Isabelle; Corinne, Alberti; Beydon, Nicole

    2015-01-01

    Forced expiratory flow (FEF) at low lung volumes are supposed to be better at detecting lung-function impairment in asthmatic children than a forced volume. The aim of this study was to examine whether FEF results could modify the interpretation of baseline and post-bronchodilator spirometry in asthmatic schoolchildren in whom forced expiratory volumes are within the normal range. Spirometry, with post-bronchodilator vital capacity within 10% of that of baseline in healthy and asthmatic children, was recorded prospectively. We defined abnormal baseline values expressed as z-scores 12%, FEF reversibility as an increase larger than the 2.5th percentile of post-bronchodilator changes in healthy children. Among 66 healthy and 50 asthmatic schoolchildren, only two (1.7%) children with normal vital capacity and no airways obstruction had abnormal baseline forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%). After bronchodilation, among the 45 asthmatic children without FEV1 reversibility, 5 (11.1%) had an FEF25-75% increase that exceeded the reference interval. Isolated abnormal baseline values or significant post-bronchodilator changes in FEF are rare situations in asthmatic schoolchildren with good spirometry quality.

  19. Effect of pentoxifylline on lung inflammation and gas exchange in a sepsis-induced acute lung injury model

    Directory of Open Access Journals (Sweden)

    I.S. Oliveira-Junior

    2006-11-01

    Full Text Available Experimental models of sepsis-induced pulmonary alterations are important for the study of pathogenesis and for potential intervention therapies. The objective of the present study was to characterize lung dysfunction (low PaO2 and high PaCO2, and increased cellular infiltration, protein extravasation, and malondialdehyde (MDA production assessed in bronchoalveolar lavage in a sepsis model consisting of intraperitoneal (ip injection of Escherichia coli and the protective effects of pentoxifylline (PTX. Male Wistar rats (weighing between 270 and 350 g were injected ip with 10(7 or 10(9 CFU/100 g body weight or saline and samples were collected 2, 6, 12, and 24 h later (N = 5 each group. PaO2, PaCO2 and pH were measured in blood, and cellular influx, protein extravasation and MDA concentration were measured in bronchoalveolar lavage. In a second set of experiments either PTX or saline was administered 1 h prior to E. coli ip injection (N = 5 each group and the animals were observed for 6 h. Injection of 10(7 or 10(9 CFU/100 g body weight of E. coli induced acidosis, hypoxemia, and hypercapnia. An increased (P < 0.05 cell influx was observed in bronchoalveolar lavage, with a predominance of neutrophils. Total protein and MDA concentrations were also higher (P < 0.05 in the septic groups compared to control. A higher tumor necrosis factor-alpha (P < 0.05 concentration was also found in these animals. Changes in all parameters were more pronounced with the higher bacterial inoculum. PTX administered prior to sepsis reduced (P < 0.05 most functional alterations. These data show that an E. coli ip inoculum is a good model for the induction of lung dysfunction in sepsis, and suitable for studies of therapeutic interventions.

  20. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Anna de Lang

    2007-08-01

    Full Text Available The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

  1. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  2. Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats

    NARCIS (Netherlands)

    Erasmus, ME; Petersen, AH; Hofstede, G; Haagsman, HP; Oetomo, SB; Prop, J

    1996-01-01

    An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was associ

  3. Effect of Ambroxol on the lung function, oxidative stress and inflammatory cytolines in AECOPD patients

    Institute of Scientific and Technical Information of China (English)

    Kaisaier Aizezi; Xiaokaiti Maimaitiyimin; Xiao-Hong Yang

    2016-01-01

    Objective:To explore the effect of Ambroxol on the lung function, oxidative stress and inflammatory factor in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:From February 2014 to August 2015, a total of 90 patients with AECOPD in our hospital were chosen as research objects and divided into observation group and control group according to their admission date with 45 cases in each group. All patients were given conventional treatment, and on this basis the observation group was given Ambroxol for 10 d. Before and after treatment, the lung function indicators (FVC, FEV1 and FEV1/FVC), the serum oxidative stress indicators (MDA and SOD) and the serum inflammatory factors (IL-6, IL-10 and TNF-α) were detected and compared, respectively.Results:After treatment, the lung function indicators FEV1, FVC and FEV1/FVC in observation group were (1.83 ± 0.25) L, (2.76 ± 0.21) L and (72.29 ± 5.10)%, respectively. Compared with before treatment and the post-treatment control group, they were significantly increased; after treatment, the oxidative stress indicator MDA in observation group was (4.24 ± 1.09) nmol/mL, while SOD was (82.20 ± 6.23) Nu/mL. Compared with before treatment and the post-treatment control group, the former was significantly reduced, while the latter was obviously increased; after treatment, the inflammatory factors IL-6 and TNF-α in the observation group were (5.15 ± 1.09) pg/mL and (3.35 ± 0.68) ng/L, respectively, while IL-10 was (7.22 ± 1.23) pg/L. Compared with before treatment and the post-treatment control group, the former two were apparently decreased, while the latter one was significantly grown.Conclusion: Ambroxol can obviously reduce the inflammatory response and significantly improve the oxidative stress and lung function in patients with AECOPD, which has positive significances in clinical.

  4. Acute functional deterioration in a child with cerebral palsy.

    LENUS (Irish Health Repository)

    Smyth, Elizabeth

    2012-01-01

    We describe a case of acute functional deterioration in a 13-year-old girl with severe spastic diplegia (GMFCS III) and a new diagnosis of diffuse intrinsic pontine glioma (DIPG). She presented with acute deterioration in mobility and motor function over 1 month, which was associated with dysarthria, dysphagia and behavioural change. Her mother had noticed subtle functional deterioration over the 2 months prior to this. Her physiotherapist who was concerned about her acute functional deterioration referred her for emergency review. Neurological imaging revealed a diffuse pontine lesion consistent with DIPG. She was subsequently referred to oncology. She deteriorated further, clinically, over the next few days and following discussion with the team; her family opted for palliative treatment, given the poor prognosis associated with DIPG.

  5. Comparison of the effects of erdosteine and N-acetylcysteine on apoptosis regulation in endotoxin-induced acute lung injury.

    Science.gov (United States)

    Demiralay, Rezan; Gürsan, Nesrin; Ozbilim, Gülay; Erdogan, Gülgün; Demirci, Elif

    2006-01-01

    This study was carried out to investigate comparatively the frequency of apoptosis in lung epithelial cells after intratracheal instillation of endotoxin [lipopolysaccharide (LPS)] in rats and the role of tumor necrosis factor alpha (TNF-alpha) on apoptosis, and the effects of erdosteine and N-acetylcysteine on the regulation of apoptosis. Female Wistar rats were given oral erdosteine (10-500 mg kg(-1)) or N-acetylcysteine (10-500 mg kg(-1)) once a day for 3 consecutive days. Then the rats were intratracheally instilled with LPS (5 mg kg(-1)) to induce acute lung injury. The rats were killed at 24 h after LPS administration. Lung tissue samples were stained with hematoxylin-eosin for histopathological assessments. The apoptosis level in the lung bronchial and bronchiolar epithelium was determined using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Cytoplasmic TNF-alpha was evaluated by immunohistochemistry. Pretreatment with erdosteine and pretreatment with N-acetylcysteine at a dose of 10 mg kg(-1) had no protective effect on LPS-induced lung injury. When the doses of drugs increased, the severity of the lung damage caused by LPS decreased. It was found that as the pretreatment dose of erdosteine was increased, the rate of apoptosis induced by LPS in lung epithelial cells decreased and this decrease was statistically significant in doses of 300 mg kg(-1) and 500 mg kg(-1). Pretreatment with N-acetylcysteine up to a dose of 500 mg kg(-1) did not show any significant effect on apoptosis regulation. It was noticed that both antioxidants had no significant effect on the local production level of TNF-alpha. These findings suggest that erdosteine could be a possible therapeutic agent for acute lethal lung injury and its mortality.

  6. Effects of resolvin D1 on inflammatory responses and oxidative stress of lipopolysaccharide-induced acute lung injury in mice

    Institute of Scientific and Technical Information of China (English)

    Wang Lei; Yuan Ruixia; Yao Chengyue; Wu Qingping; Marie Christelle; Xie Wanli; Zhang Xingcai

    2014-01-01

    Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury.Inflammation is associated with an oxidative stress reaction,which is produced in the development of airway inflammation,and which has positive feedback on inflammation itself.Resolvin D1 can reduce the infiltration of neutrophils,regulate cytokine levels and reduce the inflammation reaction,and thereby promote the resolution of inflammation.The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide (LPS)-induced acute lung injury.Methods LPS (3 mg/kg) was used to induce the acute lung injury model.Pretreatment resolvin D1 (100 ng/mouse) was given to mice 30 minutes before inducing acute lung injury.Mice were observed at 6 hours,12 hours,1 day,2 days,3 days,4 days and 7 days after LPS was administrated,then they were humanely sacrificed.We collected bronchoalveolar lavage fluid (BALF) and the lung tissues for further analysis.Paraffin section and HE staining of the lung tissues were made for histopathology observations.Parts of the lung tissues were evaluated for wet-to-dry (W/D) weight ratio.tumor necrosis factor (TNF)-α,inter leukin (IL)-1β,IL-10 and myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA).A lipid peroxidation malondialdehyde (MDA) assay kit was used to detect MDA.A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase (SOD).We determined the apoptosis of neutrophils by Flow Cytometry.A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase (HO)-1.Results Pretreatment with resolvin D1 reduced the pathological damage in the lung,decreased the recruitment of neutrophils and stimulated their apoptosis.It markedly decreased the expressions of TNF

  7. Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    Guang-ju ZHOU; Hong ZHANG; Sheng-de ZHI; Guo-ping JIANG; Jing WANG; Mao ZHANGI; Jian-xin GAN; Shao-wen XU; Guan-yu JIANG

    2007-01-01

    Aim: To evaluate the protective effect of oral raloxifene on acute lung injury.Methods: Thirty adult, male Sprague-Dawley rats each weighing 180-210 g were used and divided into 3 groups: the raloxifene-lipopolysacchadde (LPS)-HC1 group(n=10), the LPS-raloxifene-HCl group (n=10), and the placebo group (n=10). All the rats were injected intraperitoneally (ip) with 5 mg/kg LPS, and raloxifene (30mg/kg) was orally administered 1 h before and 14 h after LPS injection into the raloxifene-LPS-HCl and the LPS-raloxifene-HCl groups, respectively; the placebo group received nothing. Sixteen hours after LPS injection, all the animals were anesthetized and the femoral artery was cannulated. All the rats received a direct intratracheal (IT) injection ofHCl (pH 1.2; 0.5 mL/kg). The mean arterial pressure(MAP) and blood gas concentrations were measured. Fifteen rats (5 in each group, respectively) underwent a micro positron emission to mography (microPET)scan of the thorax 4 h after HC1 instillation. The wet/dry (W/D) weight ratio determination and histopathological examination were also performed. Results:The rats in the LPS-raloxifene-HC1 group had a lower [18F]fluorodeoxyglucose uptake compared with the rats in the placebo group (4.67±1.33 vs 9.01±1.58,respectively, P<0.01). The rats in the LPS-raloxifene-HC1 group also had a lower histological lung injury score (8.20±1.23 vs 12.6±0.97, respectively, P<0.01) and W/D weight ratio (5.335±0.198 vs 5.886±0.257, respectively, P<0.01) compared to the placebo group. The rats in this group also showed better pulmonary gas exchange and more stable mean arterial pressure (MAP) compared to the placebo group. Conclusion: Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HC1 IT instillation.

  8. Soluble Endothelial Selectin in Acute Lung Injury Complicated by Severe Pneumonia

    Directory of Open Access Journals (Sweden)

    Daisuke Osaka, Yoko Shibata, Kazunori Kanouchi, Michiko Nishiwaki, Tomomi Kimura, Hiroyuki Kishi, Shuichi Abe, Sumito Inoue, Yoshikane Tokairin, Akira Igarashi, Keiko Yamauchi, Yasuko Aida, Takako Nemoto, Keiko Nunomiya, Koji Fukuzaki, Isao Kubota

    2011-01-01

    Full Text Available Background: Pneumonia is still one of the most frequent causes of death in the elderly. Complication of acute lung injury (ALI/acute respiratory distress syndrome (ARDS by pneumonia makes patients very ill due to severe respiratory failure. Biomarkers that can discriminate the presence of complicating ALI/ARDS are required for early detection. The aim of this research was to investigate whether soluble endothelial selectin (sES could be a biomarker for ALI.Methods: Serum sES levels were measured in 27 pneumonia patients, who were enrolled between April 2006 and September 2007. Among these patients, six had ALI or a condition that was clinically comparable to ALI (cALI. All patients who were enrolled were successfully treated and survived.Results: Circulating sES levels were elevated in pneumonia patients with ALI/cALI, and sES levels decreased following treatment of their pneumonia. Univariate and multivariate logistic regression analyses showed that sES was the only significant factor for identifying complicating ALI/cALI, independently of C-reactive protein (CRP and lactate dehydrogenase (LDH. By receiver operating characteristic (ROC curve analysis, the cut-off value for sES was 40.1 ng/mL, with a sensitivity of 0.8 and a specificity of 0.8.Conclusion: sES may be a useful biomarker for discriminating complicating ALI/cALI in patients with severe pneumonia.

  9. Acute respiratory failure in critically ill patients with interstitial lung disease.

    Directory of Open Access Journals (Sweden)

    Lara Zafrani

    Full Text Available Patients with chronic known or unknown interstitial lung disease (ILD may present with severe respiratory flares that require intensive management. Outcome data in these patients are scarce.Clinical and radiological features were collected in 83 patients with ILD-associated acute respiratory failure (ARF. Determinants of hospital mortality and response to corticosteroid therapy were identified by logistic regression.Hospital and 1-year mortality rates were 41% and 54% respectively. Pulmonary hypertension, computed tomography (CT fibrosis and acute kidney injury were independently associated with mortality (odds ratio (OR 4.55; 95% confidence interval (95%CI (1.20-17.33; OR, 7.68; (1.78-33.22 and OR 10.60; (2.25-49.97 respectively. Response to steroids was higher in patients with shorter time from hospital admission to corticosteroid therapy. Patients with fibrosis on CT had lower response to steroids (OR, 0.03; (0.005-0.21. In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality.Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival.

  10. Mesenchymal Stem Cell Attenuates Neutrophil-predominant Inflammation and Acute Lung Injury in an In Vivo Rat Model of Ventilator-induced Lung Injury

    Directory of Open Access Journals (Sweden)

    Tian-Shun Lai

    2015-01-01

    Full Text Available Background: Subsequent neutrophil (polymorphonuclear neutrophil [PMN]-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI, and mesenchymal stem cell (MSC can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair of VILI. However, whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown. This study aimed to test whether MSC intervention could attenuate the PMN-predominate inflammatory in the mechanical VILI. Methods: Sprague-Dawley rats were ventilated for 2 hours with large tidal volume (20 mL/kg. MSCs were given before or after ventilation. The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation, and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation. Results: Mechanical ventilation (MV caused significant lung injury reflected by increasing in PMN pulmonary sequestration, inflammatory chemokines (tumor necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein 2 in the bronchoalveolar lavage fluid, and injury score of the lung tissue. These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity, production of radical oxygen series. MSC intervention especially pretreatment attenuated subsequent lung injury, systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation. Conclusions: MV causes profound lung injury and PMN-predominate inflammatory responses. The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.

  11. Mesenchymal Stem Cell Attenuates Neutrophil-predominant Inflammation and Acute Lung Injury in an In Vivo Rat Model of Ventilator-induced Lung Injury

    Institute of Scientific and Technical Information of China (English)

    Tian-Shun Lai; Zhi-Hong Wang; Shao-Xi Cai

    2015-01-01

    Background:Subsequent neutrophil (polymorphonuclear neutrophil [PMN])-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI),and mesenchymal stem cell (MSC) can improve mice survival model of endotoxin-induced acute lung injury,reduce lung impairs,and enhance the repair of VILI.However,whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown.This study aimed to test whether MSC intervention could attenuate the PMN-predominate inflammatory in the mechanical VILI.Methods:Sprague-Dawley rats were ventilated for 2 hours with large tidal volume (20 mL/kg).MSCs were given before or after ventilation.The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation,and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation.Results:Mechanical ventilation (MV) caused significant lung injury reflected by increasing in PMN pulmonary sequestration,inflammatory chemokines (tumor necrosis factor-alpha,interleukin-6 and macrophage inflammatory protein 2) in the bronchoalveolar lavage fluid,and injury score of the lung tissue.These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity,production of radical oxygen series.MSC intervention especially pretreatment attenuated subsequent lung injury,systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation.Conclusions:MV causes profound lung injury and PMN-predominate inflammatory responses.The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.

  12. Lung Ventilation Functional Monitoring Based on Electrical Impedance Tomography

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiaoyan; WANG Huaxiang; ZHAO Bo; SHI Xiaolei

    2009-01-01

    Medically,electrical impedance tomography(EIT)is a relatively inexpensive,safe,non-invasive and portable technique compared with computerized tomography(CT)and magnetic resonance imaging(MRI).In this paper,EIT_TJU_Ⅱ system is developed including both the data collection system and image reconstruction algorithm.The testing approach of the system performance,including spatial resolution and sensitivity,is described through brine tank experiments.The images of the thorax physical model verify that the system can reconstruct the interior resistivity distribution.Finally,the lung ventilation functional monitoring in vivo is realized by EIT,and the visualized images indicate that the configuration and performance of EIT_TJU_Ⅱ system are feasible and EIT is a promising technique in clinical monitoring application.

  13. A genetic approach to understanding asthma and lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil

    2014-01-01

    Asthma is a common heritable disease of the airways with recurrent episodes of symptoms and reversible airflow obstruction that has increased dramatically in prevalence. The disease is highly heterogeneous with varying age at onset and clinical presentation and most likely represents several...... different subtypes of disease associated with distinct clinical features, divergent underlying molecular mechanisms, and individual treatment responses. Information obtained from genetic studies may be an important way of understanding underlying disease subtypes. Genome wide association studies (GWAS) have......, related traits and objective measures in order to disentangle the underlying pathophysiological disease mechanisms for the subtypes of disease. Several genes and loci have been found to be associated with adult lung function in GWAS, but it is currently unknown at what time in life these genes exert...

  14. Lung-function trajectories leading to chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Lange, Peter; Celli, B.; Agustí, A.;

    2015-01-01

    population norms. METHODS: We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or age of patients, approximately...... at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27±18 ml per year (P...BACKGROUND: Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than...

  15. Respiratory symptoms and lung function among Danish woodworkers.

    Science.gov (United States)

    Schlünssen, Vivi; Schaumburg, Inger; Taudorf, Ebbe; Mikkelsen, Anders B; Sigsgaard, Torben

    2002-01-01

    A cross-sectional study including 54 furniture factories and three control factories was conducted to survey lung function and prevalence of respiratory symptoms among woodworkers. Spirometry was performed on 2423 persons. Questionnaires regarding respiratory symptoms and wood dust exposure were completed by 2033 woodworkers and 474 controls. Personal passive dust measurements were performed on 1579 persons. The arithmetic mean +/- SD for equivalent inhalable dust was relatively low (1.19 +/- 0.86 mg/m3). Woodworkers had increased frequency of coughing with negative interaction between dust exposure and smoking. A dose-response relationship was seen between dust exposure and asthma symptoms, and a positive interaction for asthma was seen between female gender and dust exposure. Increased frequency of wheezing and a cross-shift decrease in forced expiratory volume in 1 second among workers using pinewood was seen. In conclusion, wood dust exposure might cause respiratory symptoms, despite a relatively low exposure level.

  16. Atomization Inhalation of Terbutaline and Budesonide Efficiently Improved Immunity and Lung Function of AECOPD Patients

    Institute of Scientific and Technical Information of China (English)

    Guilan Xiong; Lijun Xu; Liu Wei; Xiaodan Li

    2008-01-01

    Chronic obstructive pulmonary disease (COPD) is a syndrome of chronic progressive airflow limitation as a result of chronic inflammation of the airways and lung parenchyma. COPD patients always have airway hyperreactivity (AHR), so how to reduce AHR becomes the key purpose of clinical treatment. It is hypothesized that combined inhalation of corticosteroids andβ2-agonists can reduce the AHR in COPD. In this study, atomization inhalation of budesonide and terbutaline plus conventional therapies was applied to treat AECOPD (acute exacerbation of chronic obstructive pulmonary disease) patients for two weeks. The results showed that additional inhalation of budesonide and terbutaline could upregulate serum IL-2 levels, the percentages of CD3+ T and CD4+ T cells, and CD4/CD8 ratio, and decrease eosinophils and serum CRP level more efficiently than conventional treatment in patients with AECOPD. And the lung function of the atomization inhalation group was improved more obviously after the treatment compared with the conventional treatment group. Thus, atomization inhalation of terbutaline and budesonide can control AECOPD effectively, and has wide clinical perspective in controlling and preventing the exacerbation of COPD. Cellular & Molecular Immunology. 2008;5(4):287-291.

  17. Fibroblast Growth Factor-10 (FGF-10) Mobilizes Lung-resident Mesenchymal Stem Cells and Protects Against Acute Lung Injury.

    Science.gov (United States)

    Tong, Lin; Zhou, Jian; Rong, Linyi; Seeley, Eric J; Pan, Jue; Zhu, Xiaodan; Liu, Jie; Wang, Qin; Tang, Xinjun; Qu, Jieming; Bai, Chunxue; Song, Yuanlin

    2016-02-12

    FGF-10 can prevent or reduce lung specific inflammation due to traumatic or infectious lung injury. However, the exact mechanisms are poorly characterized. Additionally, the effect of FGF-10 on lung-resident mesenchymal stem cells (LR-MSCs) has not been studied. To better characterize the effect of FGF-10 on LR-MSCs, FGF-10 was intratracheally delivered into the lungs of rats. Three days after instillation, bronchoalveolar lavage was performed and plastic-adherent cells were cultured, characterized and then delivered therapeutically to rats after LPS intratracheal instillation. Immunophenotyping analysis of FGF-10 mobilized and cultured cells revealed expression of the MSC markers CD29, CD73, CD90, and CD105, and the absence of the hematopoietic lineage markers CD34 and CD45. Multipotency of these cells was demonstrated by their capacity to differentiate into osteocytes, adipocytes, and chondrocytes. Delivery of LR-MSCs into the lungs after LPS injury reduced the inflammatory response as evidenced by decreased wet-to-dry ratio, reduced neutrophil and leukocyte recruitment and decreased inflammatory cytokines compared to control rats. Lastly, direct delivery of FGF-10 in the lungs of rats led to an increase of LR-MSCs in the treated lungs, suggesting that the protective effect of FGF-10 might be mediated, in part, by the mobilization of LR-MSCs in lungs.

  18. Effect of resveratrol on microcirculation disorder and lung injury following severe acute pancreatitis in rats

    Institute of Scientific and Technical Information of China (English)

    Yong Meng; Mei Zhang; Jun Xu; Xue-Min Liu; Qing-Yong Ma

    2005-01-01

    AIM: To investigate the mechanism of resveratrol underlying the microcirculation disorder and lung injury following severe acute pancreatitis (SAP).METHODS: Twenty-four rats were divided into 3 groups (SAP, sham and resveratrol groups) randomly. SAP model was established by injecting 4% sodium taurocholate 1 mL/kg through puncturing pancreatic ducts. Sham (control) group (8 rats) was established by turning over the duodenum.Resveratrol was given at 0.1 mg/kg b.m. intraperitoneally.Rats were sacrificed 9 h after SAP was induced. Blood samples were obtained for hemorrheological examination.Lung tissues were used for pathological observation, and examination of microvascular permeability, dry/wet ratio and myeloperoxidase (MPO) activity. Gene expression of intercellular adhesion molecule-1 (ICAM-1) was detected by RT-PCR.RESULTS: Compared with SAP group, resveratrol relieved the edema and infiltration of leukocytes in the lungs. Resveratrol improved markers of hemorrheology:high VTB (5.77±1.18 mPas vs9.49±1.34 mPas), low VTB (16.12±3.20 mPas vs30.91±7.28 mPas), PV (4.69±1.68 mPas vs8.00±1.34 mPas), BSR (1.25±0.42 mm/h vs 0.03±0.03mm/h), VPC (54.67±3.08% vs 62.17±3.39%), fibrinogen (203.2±87.8 g/L vs 51.3±19.1 g/L), original hemolysis (0.45±0.02 vs 0.49±0.02), and complete hemolysis (0.41±0.02 vs0.43±0.02) (P<0.05). Resveratrol decreased the OD ratio of ICAM-1 gene (0.800±0.03 vs 1.188±0.10),dry/wet ratio (0.74±0.02 vs 0.77±0.03), microvascular permeability (0.079±0.006 vs 0.112±0.004) and MPO activity (4.42±0.32 vs 5.03±0.51) significantly (P<0.05).CONCLUSION: Resveratrol can improve the microcirculation disorder of the lung by decreasing leukocyte-endothelial interaction, reducing blood viscosity, improving the decrease of blood flow, and stabilizing erythrocytes in SAP rats. It may be a potential candidate to treat SAP and its severe complications (ALI).

  19. Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats.

    Science.gov (United States)

    Feng, Guang; Jiang, Ze-yu; Sun, Bo; Fu, Jie; Li, Tian-zuo

    2016-02-01

    Acute lung injury (ALI), a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. Fisetin, a natural flavonoid from fruits and vegetables, was reported to have wide pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was to detect the effects of fisetin on lipopolysaccharide (LPS)-induced acute lung injury and investigate the potential mechanism. Fisetin was injected (1, 2, and 4 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). Our results showed that fisetin effectively reduced the inflammatory cytokine release and total protein in bronchoalveolar lavage fluids (BALF), decreased the lung wet/dry ratios, and obviously improved the pulmonary histology in LPS-induced ALI. Furthermore, fisetin inhibited LPS-induced increases of neutrophils and macrophage infiltration and attenuated MPO activity in lung tissues. Additionally, fisetin could significantly inhibit the Toll-like receptor 4 (TLR4) expression and the activation of NF-κB in lung tissues. Our data indicates that fisetin has a protective effect against LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment.

  20. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1.

    Directory of Open Access Journals (Sweden)

    Shirley H J Mei

    2007-09-01

    Full Text Available BACKGROUND: The acute respiratory distress syndrome (ARDS, a clinical complication of severe acute lung injury (ALI in humans, is a leading cause of morbidity and mortality in critically ill patients. ALI is characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema associated with a proteinaceous alveolar exudate. Current specific treatment strategies for ALI/ARDS are lacking. We hypothesized that mesenchymal stem cells (MSCs, with or without transfection with the vasculoprotective gene angiopoietin 1 (ANGPT1 would have beneficial effects in experimental ALI in mice. METHODS AND FINDINGS: Syngeneic MSCs with or without transfection with plasmid containing the human ANGPT1 gene (pANGPT1 were delivered through the right jugular vein of mice 30 min after intratracheal instillation of lipopolysaccharide (LPS to induce lung injury. Administration of MSCs significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts in bronchoalveolar lavage (BAL fluid (53%, 95% confidence interval [CI] 7%-101%; and 60%, CI 4%-116%, respectively as well as reducing levels of proinflammatory cytokines in both BAL fluid and lung parenchymal homogenates. Furthermore, administration of MSCs transfected with pANGPT1 resulted in nearly complete reversal of LPS-induced increases in lung permeability as assessed by reductions in IgM and albumin levels in BAL (96%, CI 6%-185%; and 74%, CI 23%-126%, respectively. Fluorescently tagged MSCs were detected in the lung tissues by confocal microscopy and flow cytometry in both naïve and LPS-injured animals up to 3 d. CONCLUSIONS: Treatment with MSCs alone significantly reduced LPS-induced acute pulmonary inflammation in mice, while administration of pANGPT1-transfected MSCs resulted in a further improvement in both alveolar inflammation and permeability. These results suggest a potential role for cell-based ANGPT1 gene therapy

  1. Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS production.

    Directory of Open Access Journals (Sweden)

    John W Semple

    Full Text Available Transfusion-related acute lung injury (TRALI is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature and respiratory distress (dyspnea were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage.

  2. Proteasome function is not impaired in healthy aging of the lung.

    Science.gov (United States)

    Caniard, Anne; Ballweg, Korbinian; Lukas, Christina; Yildirim, Ali Ö; Eickelberg, Oliver; Meiners, Silke

    2015-10-01

    Aging is the progressive loss of cellular function which inevitably leads to death. Failure of proteostasis including the decrease in proteasome function is one hallmark of aging. In the lung, proteasome activity was shown to be impaired in age-related diseases such as chronic obstructive pulmonary disease. However, little is known on proteasome function during healthy aging. Here, we comprehensively analyzed healthy lung aging and proteasome function in wildtype, proteasome reporter and immunoproteasome knockout mice. Wildtype mice spontaneously developed senile lung emphysema while expression and activity of proteasome complexes and turnover of ubiquitinated substrates was not grossly altered in lungs of aged mice. Immunoproteasome subunits were specifically upregulated in the aged lung and the caspase-like proteasome activity concomitantly decreased. Aged knockout mice for the LMP2 or LMP7 immunoproteasome subunits showed no alteration in proteasome activities but exhibited typical lung aging phenotypes suggesting that immunoproteasome function is dispensable for physiological lung aging in mice. Our results indicate that healthy aging of the lung does not involve impairment of proteasome function. Apparently, the reserve capacity of the proteostasis systems in the lung is sufficient to avoid severe proteostasis imbalance during healthy aging.

  3. Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome.

    Science.gov (United States)

    Gongora, Maria Carolina; Lob, Heinrich E; Landmesser, Ulf; Guzik, Tomasz J; Martin, W David; Ozumi, Kiyoski; Wall, Susan M; Wilson, David Scott; Murthy, Niren; Gravanis, Michael; Fukai, Tohru; Harrison, David G

    2008-10-01

    The extracellular superoxide dismutase 3 (SOD3) is highly expressed in both blood vessels and lungs. In different models of pulmonary injury, SOD3 is reduced; however, it is unclear whether this contributes to lung injury. To study the role of acute SOD3 reduction in lung injury, the SOD3 gene was deleted in adult mice by using the Cre-Lox technology. Acute reduction of SOD3 led to a fivefold increase in lung superoxide, marked inflammatory cell infiltration, a threefold increase in the arterial-alveolar gradient, respiratory acidosis, histological changes similar to those observed in adult respiratory distress syndrome, and 85% mortality. Treatment with the SOD mimetic MnTBAP and intranasal administration of SOD-containing polyketal microparticles reduced mortality, prevented the histological alterations, and reduced lung superoxide levels. To understand how mice with the SOD3 embryonic deletion survived without lung injury, gene array analysis was performed. These data demonstrated the up-regulation of 37 genes and down-regulation of nine genes, including those involved in cell signaling, inflammation, and gene transcription in SOD3-/- mice compared with either mice with acute SOD3 reduction or wild-type controls. These studies show that SOD3 is essential for survival in the presence of ambient oxygen and that acute loss of this enzyme can lead to severe lung damage. Strategies either to prevent SOD3 inactivation or to augment its levels might prove useful in the treatment of acute lung injury.

  4. Gas cooking is associated with small reductions in lung function in children.

    NARCIS (Netherlands)

    Moshammer, H.; Fletcher, T.; Heinrich, J.; Hoek, G.; Hruba, F.; Pattenden, S.; Rudnai, P.; Slachtova, H.; Speizer, F.E.; Zlotkowska, R.; Neuberger, M.

    2010-01-01

    Inconsistent effects of gas cooking on lung function have been reported. In a previous study from Austria, we demonstrated a significant, though small, reduction of lung function parameters in children living in homes with gas stoves. We used a larger international database to check if this finding

  5. Superoxide Dismutase 3 Polymorphism Associated with Reduced Lung Function in Two Large Populations

    DEFF Research Database (Denmark)

    Dahl, Morten; Bowler, Russell P; Juul, Klaus

    2008-01-01

    Rationale: Superoxide dismutase (SOD) 3 inhibits oxidative fragmentation of lung matrix components Collagen 1, hyaluronan, and heparan sulfate. Inherited change in SOD3 expression or function could affect lung matrix homeostasis and influence pulmonary function. Objectives: To identify novel SOD3...

  6. First case of atypical takotsubo cardiomyopathy in a bilateral lung-transplanted patient due to acute respiratory failure.

    Science.gov (United States)

    Ghadri, Jelena R; Bataisou, Roxana D; Diekmann, Johanna; Lüscher, Thomas F; Templin, Christian

    2015-10-01

    Takotsubo cardiomyopathy which is characterised by a transient left ventricular wall motion abnormality was first described in 1990. The disease is still not well known, and as such it is suggested that an emotional trigger is mandatory in this disease. We present the case of a 51-year old female patient seven years after bilateral lung transplantation, who developed acute respiratory distress syndrome and subsequently suffered from atypical takotsubo cardiomyopathy with transient severe reduction of ejection fraction and haemodynamic instability needing acute intensive care treatment. Acute respiratory failure has emerged as an important physical trigger factor in takotsubo cardiomyopathy. Little is known about the association of hypoxia and takotsubo cardiomyopathy which can elicit a life-threatening condition requiring acute intensive care. Therefore, experimental studies are needed to investigate the role of hypoxia in takotsubo cardiomyopathy.

  7. Effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Mao ZR

    2016-02-01

    Full Text Available Zhengrong Mao,1 Haifeng Wang2,3 1Department of Critical Care Medicine, The First Affiliated Hospital of Henan, University of Traditional Chinese Medicine, 2Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, 3Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Zhengzhou City, Henan, People’s Republic of China Objective: To observe the effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome. Subjects and methods: A total of 53 patients with exogenous pulmonary acute respiratory distress syndrome, who were admitted to the intensive care unit of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from March 2009 to February 2013, were selected. They were randomly divided into the treatment group (25 cases and the control group (28 cases. Both the groups were treated with conventional treatment and lung-protective ventilation strategy; apart from these, enema therapy with Xuanbai Chengqi decoction was given to the treatment group. Meanwhile, static lung compliance, dynamic lung compliance, peak airway pressure, plateau pressure, and positive end-expiratory pressure (PEEP for patients in both the groups were observed and recorded at 24, 48, and 72 hours after the drug was used. Moreover, variations in the duration of parenteral nutrition, incidence rate of complications, and case fatality rate in patients after treatment were recorded. Results: For patients in the treatment group, at 48 and 72 hours after treatment, the static lung compliance and dynamic lung compliance were significantly higher than those in the control group, while plateau pressure, peak airway pressure, and PEEP were significantly lower than those before treatment. At the same time, PEEP for patients in the treatment group at 72

  8. Reduction of Pulmonary Function After Surgical Lung Resections of Different Volume

    Science.gov (United States)

    Cukic, Vesna

    2014-01-01

    Introduction: In recent years an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused with common etiologic factor - smoking cigarettes. Objective: To determine how big the loss of lung function is after surgical resection of lung of different range. Methods: The study was done on 58 patients operated at the Clinic for thoracic surgery KCU Sarajevo, previously treated at the Clinic for pulmonary diseases “Podhrastovi” in the period from 01.06.2012. to 01.06.2014. The following resections were done: pulmectomy (left, right), lobectomy (upper, lower: left and right). The values of postoperative pulmonary function were compared with preoperative ones. As a parameter of lung function we used FEV1 (forced expiratory volume in one second), and changes in FEV1 are expressed in liters and in percentage of the recorded preoperative and normal values of FEV1. Measurements of lung function were performed seven days before and 2 months after surgery. Results: Postoperative FEV1 was decreased compared to preoperative values. After pulmectomy the maximum reduction of FEV1 was 44%, and after lobectomy it was 22% of the preoperative values. Conclusion: Patients with airway obstruction are limited in their daily life before the surgery, and an additional loss of lung tissue after resection contributes to their inability. Potential benefits of lung resection surgery should be balanced in relation to postoperative morbidity and mortality. PMID:25568542

  9. Utility of SPECT Lung Perfusion Scans in Assessing the Early Changes in Pulmonary Function after Radiotherapy for Patients with Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Wenjie Zhang; Rong Zheng; Luiun Zhao; Luhua Wang; Shengzu Chen

    2005-01-01

    OBJECTIVE Radiation-induced lung injury commonly follows radiotherapy (RT) fortumors within and near the thorax. Lung function is usually measured by pulmonary function tests (PFTs). But RT-induced regional changes of pulmonary function cannot be accurately evaluated by PFTs. Lung perfusion scintigraphy compared with other radiographic methods can assess well regional pulmonary physiological function, and a 3-dimensional conformal radiotherapy planning system can quantitatively calculate irradiation dosage. The purpose of this study is to assess, by lung perfusion scintigraphy, early changes in the pulmonary function of patients with lung cancer when receiving thoracic 3-dimensional conformal radiotherapy (3D-CRT).METHODS Nineteen patients receiving thoracic 3D-CRT for lung cancer were studied. A single photon emission computed tomography (SPECT)lung perfusion scan, X-ray or CT scan before RT and after 40~50Gy radiation were performed. Pre-RT SPECT lung perfusion images were classified by comparing lung perfusion defects with radiological abnormalities before RT. Grade 0: There was no lung perfusion defect in the area of radiological abnormality. Grade 1: The size of the radiological abnormality was similar to the area of the lung perfusion defect. Grade 2: The area of the lung perfusion defect was bigger than the size of the radiological abnormality and extended to one lobe of the lung. Grade 3: The area of lung perfusion defect exceeded one lobe of the lung. The radiation field with more than 20 Gy was drawn as a region of interest (ROI). The proportion of radioactive dose within this ROI relative to total lung dose in one slice was calculated.RESULTS All patients had lung perfusion defects, nine patients with grade 1,five patients with grade 2 and five patients with grade 3 damage,respectively. All tumors in the 19 patients were reduced in CT or X-ray images to various degrees after 40~50 Gy radiation. The mean proportion of ROI in 19 patients was 53.7±29

  10. Forward lunge as a functional performance test in ACL deficient subjects: test-retest reliability

    DEFF Research Database (Denmark)

    Alkjaer, Tine; Henriksen, Marius; Dyhre-Poulsen, Poul;

    2009-01-01

    The forward lunge movement may be used as a functional performance test of anterior cruciate ligament (ACL) deficient and reconstructed subjects. The purposes were 1) to determine the test-retest reliability of a forward lunge in healthy subjects and 2) to determine the required numbers of repeti......The forward lunge movement may be used as a functional performance test of anterior cruciate ligament (ACL) deficient and reconstructed subjects. The purposes were 1) to determine the test-retest reliability of a forward lunge in healthy subjects and 2) to determine the required numbers...

  11. Viral bronchiolitis in young rats causes small airway lesions that correlate with reduced lung function.

    Science.gov (United States)

    Sorkness, Ronald L; Szakaly, Renee J; Rosenthal, Louis A; Sullivan, Ruth; Gern, James E; Lemanske, Robert F; Sun, Xin

    2013-11-01

    Viral illness with wheezing during infancy is associated with the inception of childhood asthma. Small airway dysfunction is a component of childhood asthma, but little is known about how viral illness at an early age may affect the structure and function of small airways. We used a well-characterized rat model of postbronchiolitis chronic airway dysfunction to address how postinfectious small airway lesions affect airway physiological function and if the structure/function correlates persist into maturity. Brown Norway rats were sham- or virus inoculated at 3 to 4 weeks of age and allowed to recover from the acute illness. At 3 to 14 months of age, physiology (respiratory system resistance, Newtonian resistance, tissue damping, and static lung volumes) was assessed in anesthetized, intubated rats. Serial lung sections revealed lesions in the terminal bronchioles that reduced luminal area and interrupted further branching, affecting 26% (range, 13-39%) of the small airways at 3 months of age and 22% (range, 6-40%) at 12 to 14 months of age. At 3 months of age (n = 29 virus; n = 7 sham), small airway lesions correlated with tissue damping (rs = 0.69) but not with Newtonian resistance (rs = 0.23), and Newtonian resistance was not elevated compared with control rats, indicating that distal airways were primarily responsible for the airflow obstruction. Older rats (n = 7 virus; n = 6 sham) had persistent small airway dysfunction and significantly increased Newtonian resistance in the postbronchiolitis group. We conclude that viral airway injury at an early age may induce small airway lesions that are associated quantitatively with small airway physiological dysfunction early on and that these defects persist into maturity.

  12. Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Matsuda Akihisa

    2012-08-01

    Full Text Available Abstract Background A previous meta-analysis reported a positive association between an insertion/deletion (I/D polymorphism in the angiotensin-converting enzyme gene (ACE and the risk of acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. Methods We searched electronic databases through October 2011 for the terms “angiotensin-converting enzyme gene”, “acute lung injury”, and “acute respiratory distress syndrome,” and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. Results The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects ( Pallele Pdominant = 0.001, Precessive = 0.002. This finding remained significant after correction for multiple comparisons. Conclusions There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.

  13. The role of iron in Libby amphibole-induced acute lung injury and inflammation.

    Science.gov (United States)

    Shannahan, Jonathan H; Ghio, Andrew J; Schladweiler, Mette C; McGee, John K; Richards, Judy H; Gavett, Stephen H; Kodavanti, Urmila P

    2011-05-01

    Complexation of host iron (Fe) on the surface of inhaled asbestos fibers has been postulated to cause oxidative stress contributing to in vivo pulmonary injury and inflammation. We examined the role of Fe in Libby amphibole (LA; mean length 4.99 µm ± 4.53 and width 0.28 µm ± 0.19) asbestos-induced inflammogenic effects in vitro and in vivo. LA contained acid-leachable Fe and silicon. In a cell-free media containing FeCl(3), LA bound #17 µg of Fe/mg of fiber and increased reactive oxygen species generation #3.5 fold, which was reduced by deferoxamine (DEF) treatment. In BEAS-2B cells exposure to LA, LA loaded with Fe (FeLA), or LA with DEF did not increase HO-1 or ferritin mRNA expression. LA increased IL-8 expression, which was reduced by Fe loading but increased by DEF. To determine the role of Fe in LA-induced lung injury in vivo, spontaneously hypertensive rats were exposed intratracheally to either saline (300 µL), DEF (1 mg), FeCl(3) (21 µg), LA (0.5 mg), FeLA (0.5 mg), or LA + DEF (0.5 mg). LA caused BALF neutrophils to increase 24 h post-exposure. Loading of Fe on LA but not chelation slightly decreased neutrophilic influx (LA + DEF > LA > FeLA). At 4 h post-exposure, LA-induced lung expression of MIP-2 was reduced in rats exposed to FeLA but increased by LA + DEF (LA + DEF > LA > FeLA). Ferritin mRNA was elevated in rats exposed to FeLA compared to LA. In conclusion, the acute inflammatory response to respirable fibers and particles may be inhibited in the presence of surface-complexed or cellular bioavailable Fe. Cell and tissue Fe-overload conditions may influence the pulmonary injury and inflammation caused by fibers.

  14. Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury.

    Science.gov (United States)

    Santana, Maria Cristina E; Garcia, Cristiane S N B; Xisto, Débora G; Nagato, Lilian K S; Lassance, Roberta M; Prota, Luiz Felipe M; Ornellas, Felipe M; Capelozzi, Vera L; Morales, Marcelo M; Zin, Walter A; Pelosi, Paolo; Rocco, Patricia R M

    2009-06-30

    Prone position may delay the development of ventilator-induced lung injury (VILI), but the mechanisms require better elucidation. In experimental mild acute lung injury (ALI), arterial oxygen partial pressure (Pa O2), lung mechanics and histology, inflammatory markers [interleukin (IL)-6 and IL-1 beta], and type III procollagen (PCIII) mRNA expressions were analysed in supine and prone position. Wistar rats were randomly divided into two groups. In controls, saline was intraperitoneally injected while ALI was induced by paraquat. After 24-h, the animals were mechanically ventilated for 1-h in supine or prone positions. In ALI, prone position led to a better blood flow/tissue ratio both in ventral and dorsal regions and was associated with a more homogeneous distribution of alveolar aeration/tissue ratio reducing lung static elastance and viscoelastic pressure, and increasing end-expiratory lung volume and Pa O2. PCIII expression was higher in the ventral than dorsal region in supine position, with no regional changes in inflammatory markers. In conclusion, prone position may protect the lungs against VILI, thus reducing pulmonary stress and strain.

  15. Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.L. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Hu, G.C. [Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL (United States); Zhu, S.S. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Li, J.F. [Department of Anesthesiology, Tengzhou Central People' s Hospital, Liaocheng, Shandong Province (China); Liu, G.J. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China)

    2014-10-14

    The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.

  16. Roger S. Mitchell lecture. Uses of expression microarrays in studies of pulmonary fibrosis, asthma, acute lung injury, and emphysema.

    Science.gov (United States)

    Sheppard, Dean

    2002-03-01

    Expression microarrays are a powerful tool that could provide new information about the molecular pathways regulating common lung diseases. To exemplify how this tool can be useful, selected examples of informative experiments are reviewed. In studies relevant to asthma, the cytokine interleukin-13 has been shown to produce many of the phenotypic features of this disease, but the cellular targets in the airways and the molecular pathways activated are largely unknown. We have used microarrays to begin to dissect the different transcriptional responses of primary lung cells to this cytokine. In experiments designed to identify global transcriptional programs responsible for regulating lung inflammation and pulmonary fibrosis, we performed microarray experiments on lung tissue from wild-type mice and mice lacking a member of the integrin family know to be involved in activation of latent transforming growth factor (TGF)-beta. In addition to identifying distinct cluster of genes involved in each of these processes, these studies led to the identification of novel pathways by which TGF-beta can regulate acute lung injury and emphysema. Together, these examples demonstrate how careful application and thorough analysis of expression microarrays can facilitate the discovery of novel molecular targets for intervening in common lung diseases.

  17. Analysis of clinical risk factors associated with mortality of severely injured multiple trauma patients with acute lung injury

    Institute of Scientific and Technical Information of China (English)

    MA Yue-feng; SHENG Lei; GU Jun; ZHANG Mao; JIANG Guan-yu

    2009-01-01

    Background It is important to study the factors affecting the clinical mortality of the severe multiple trauma population. The present study was aimed to identify the potential risk factors that could affect mortality rate of acute lung injury (ALI) in severely injured multiple trauma population and to investigate the effects of certain risk factors on the prognosis of different patient subpopulations.Methods This is a follow-up study treating trauma as a single cause for emergency department (ED) and emergency intensive care unit (EICU) admissions. Patients identified with severe multiple trauma with early onset of ALI were enrolled from five trauma centers. Nineteen potential risk factors affecting the prognosis of ALI were examined by univariate and multivariate Logistic regression analyses to identify the ones that affected the mortality of these severe multiple trauma patients.Results There were 687 multiple trauma patients with post-traumatic ALl admitted to ED and EICU during the study period. The six risk factors that affected the mortality with unadjusted odd ratios (ORs) and 95% confidence intervals (Cls)were Acute Physiology Score and Chronic Health Evaluation Score (APACHE) II score, Injury Severity Score (ISS), duration of trauma, age, aspiration of gastric contents, and disseminated intravascular coagulation (DIC). Specific risk factors also affected different patient subpopulations at different degrees (surviving beyond 24 hours, 72 hours, 28 days and with multiple blood transfusions and higher injury scores).Conclusions Factors of APACHE Ⅱ score, ISS and aspiration of gastric contents that could predict the mortality of ALI may exist in the early stage of trauma. Duration of trauma and DIC that greatly affected and predicted the short- and long-term development and mortality of ALI deserve special attention. Elderly patients (aged beyond 65 years) were the independent risk factor for the secondary sepsis and deterioration of pulmonary function

  18. LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION

    Science.gov (United States)

    Chen, Kun; Hoffman, Eric A.; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

    2017-01-01

    The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the “normal” subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors.

  19. The association of systemic microvascular changes with lung function and lung density: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Bianca Harris

    Full Text Available Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45-84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV(1 (P<0.001 and FEV(1/forced vital capacity (FVC ratio (P = 0.04. Albumin-to-creatinine ratio was inversely associated with FEV(1 (P = 0.002 but not FEV(1/FVC. Myocardial blood flow (n = 126 was associated with lower FEV(1 (P = 0.02, lower FEV(1/FVC (P = 0.001 and greater percentage LAA (P = 0.04. Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.

  20. Does acute exposure to aldehydes impair pulmonary function and structure?

    Science.gov (United States)

    Abreu, Mariana de; Neto, Alcendino Cândido; Carvalho, Giovanna; Casquillo, Natalia Vasconcelos; Carvalho, Niedja; Okuro, Renata; Ribeiro, Gabriel C Motta; Machado, Mariana; Cardozo, Aléxia; Silva, Aline Santos E; Barboza, Thiago; Vasconcellos, Luiz Ricardo; Rodrigues, Danielle Araujo; Camilo, Luciana; Carneiro, Leticia de A M; Jandre, Frederico; Pino, Alexandre V; Giannella-Neto, Antonio; Zin, Walter A; Corrêa, Leonardo Holanda Travassos; Souza, Marcio Nogueira de; Carvalho, Alysson R

    2016-07-15

    Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1β, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.

  1. Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma.

    Directory of Open Access Journals (Sweden)

    Jason D Christie

    Full Text Available Acute Lung Injury (ALI is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1, we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs at p<0.01 to a replication phase (Phase 2 comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3 using expression quantitative trait loci (eQTL analyses in stimulated B-lymphoblastoid cell lines (B-LCL in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021. PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.

  2. α1-ANTITRYPSIN ATTENUATES ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN RABBITS

    Institute of Scientific and Technical Information of China (English)

    揭志军; 蔡映云; 杨文兰; 金美玲; 朱威; 祝慈芳

    2003-01-01

    Objective To investigate whether pretreatment with α1-AT can attenuate acute lung injury (ALI) in rabbits induced with endotoxin. Methods Thirty-two New Zealand rabbits were randomly assigned to four groups(n=8):1.Infusion of endotoxin(Lipopolysaccharide,LPS 500μg/kg)without α1-AT (group LPS).2.Infusion α1-AT 120mg/kg at 15min before challenge with LPS(group LAV).3.Infusion of α1-AT 120mg/kg(group AAT).4 Infusion of saline 4ml/kg as control (group NS).Arterial blood gases,peripheral leukocyte counts and airway pressure were recorded every 1h.Physiologic intrapulmonary shunting (Qs/Qt) was measured every 4h.After 8h the bloods were collected for measurement of plasma concentration and activity of α1-AT.Then bronchoalveolar lavage fluid (BALF)was collected for measurement of concentrations of total protein (TP),interleukin-8(IL-8),tumor necrosis factor(TNF-α),the activities of elastase-like and α1-AT,total phospholipids(TPL) and disaturated phosphatidylcholine (DSPC).In addition,the wet-to-dry lung weight ratio(W/D) was measured. Results After infusion of endotoxin,it was observed that PaO2,peripheral luekocyte counts,total respiratory compliance progressively decreased and Ppeak and Qs/Qt increased comparing with the baseline values.In contrast to group NS,the increased plasma concentration but reduced activity of α1-AT was found in group LPS.In the BALF,the activity of α1-AT,TPL,DSPC/TPL were lower,but the concentrations of albumin,IL-8,TNF-α,and the activity of NE were higher.The ratio of W/D also increased.The pretreatment of α1-AT attenuated the deterioration of oxygenation,the reduction of compliance and the deterioration of other physiological,biochemical parameters mentioned above. Conclusion Pretreatment with α1-AT could attenuate endotoxin-induced lung injury in rabbits.Those beneficial effects of α1-AT might be due in part to the inhibitory effect on neutrophil elastase.

  3. Lung MRI and impairment of diaphragmatic function in Pompe disease

    DEFF Research Database (Denmark)

    Wens, Stephan C A; Ciet, Pierluigi; Perez-Rovira, Adria;

    2015-01-01

    manually segmented. After normalization for lung size, changes in lung dimensions between inspiration and expiration were used for analysis; normalization was based on the cranial-caudal length ratio (representing vertical diaphragmatic displacement), and the anterior-posterior and left-right length ratios...

  4. Structural and functional lung disease in primary ciliary dyskinesia

    NARCIS (Netherlands)

    F. Santamaria (Francesca); S. Montella (Silvia); H.A.W.M. Tiddens (Harm); G. Guidi (Guido); V. Casotti (Valeria); M. Maglione (Marco); P.A. de Jong (Pim)

    2008-01-01

    textabstractBackground: High-resolution CT (HRCT) scan data on primary ciliary dyskinesia (PCD) related lung disease are scarce. Study objectives: We evaluated the lung disease in children and adults with PCD by a modified Brody composite HRCT scan score to assess the prevalence of the structural ab

  5. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.

    Science.gov (United States)

    Ribeiro, Alison; Ferraz-de-Paula, Viviane; Pinheiro, Milena L; Vitoretti, Luana B; Mariano-Souza, Domenica P; Quinteiro-Filho, Wanderley M; Akamine, Adriana T; Almeida, Vinícius I; Quevedo, João; Dal-Pizzol, Felipe; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Palermo-Neto, João

    2012-03-05

    Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor.

  6. A prophylactic fresh frozen plasma transfusion leads to a possible case of transfusion-related acute lung injury.

    Science.gov (United States)

    Banerjee, Debasree; Hussain, Rashid; Mazer, Jeffrey; Carino, Gerardo

    2014-01-01

    A 39-year-old man with cholangiocarcinoma presented with fever and abdominal pain. He was hypotensive, jaundiced and had right upper quadrant tenderness. Laboratory testing showed a leucocytosis, elevated liver function tests, total bilirubin and International Normalised Ratio (INR). Given the concern for cholangitis, the patient was given antibiotics and three units of fresh frozen plasma (FFP) before biliary drain placement. After drain placement, and within 3 h of receiving blood products, the patient became tachypnoeic and hypoxic with a chest X-ray revealing new bilateral airspace disease. The rapid development of respiratory distress was determined to most likely be transfusion-related acute lung injury (TRALI). He rapidly progressed to intubation and required 100% FiO2, high positive-end expiratory pressure (PEEP) and intermittent-prone ventilation for 48 h but eventually recovered and was extubated. TRALI is an under-recognised aetiology for respiratory distress in the critically ill. Adopting a conservative transfusion strategy may prevent TRALI.

  7. Proceedings of the Workshop on Acute Lung Injury and Pulmonary Edema Held in Aberdeen Proving Ground, Maryland on 4-5 May 1989

    Science.gov (United States)

    1989-11-01

    with side effects, including pulmonary edema . The objective of this study was to determine if the pulmonary edema was cardiogenic or noncardio- genic...Proeedings ~FL gof the .1Workshop on Acute Lung Injury and Pulmonary Edema 4-5 May 1989a Aberdeen Proving Ground, Maryland I7 21 Sponsored by the...TITLE (include Security Classification) (U) Proceedings of the" Workshop on Acute Lung Injury and Pulmonary Edema , May 1989 12. PERSONAL AUTHOR(S) David

  8. Plantamajoside ameliorates lipopolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation.

    Science.gov (United States)

    Wu, Haichong; Zhao, Gan; Jiang, Kangfeng; Chen, Xiuying; Zhu, Zhe; Qiu, Changwei; Li, Chengye; Deng, Ganzhen

    2016-06-01

    Despite developments in the knowledge and therapy of acute lung injury in recent decades, mortality remains high, and there is usually a lack of effective therapy. Plantamajoside, a major ingredient isolated from Plantago asiatica L. (Plantaginaceae), has been reported to have potent anti-inflammatory properties. However, the effect of plantamajoside on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice has not been investigated. The present study aimed to reveal the potential mechanism responsible for the anti-inflammatory effects of plantamajoside on LPS-induced acute lung injury in mice and in RAW264.7 cells. The results of histopathological changes as well as the lung wet-to-dry ratio and myeloperoxidase (MPO) activity showed that plantamajoside ameliorated the lung injury that was induced by LPS. qPCR and ELISA assays demonstrated that plantamajoside suppressed the production of IL-1β, IL-6 and TNF-α in a dose-dependent manner. TLR4 is an important sensor in LPS infection. Molecular studies showed that the expression of TLR4 was inhibited by plantamajoside administration. Further study was conducted on nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) using pathways using western blots. The results showed that plantamajoside inhibited the phosphorylation of IκBα, p65, p38, JNK and ERK. All results indicated that plantamajoside has protective effect on LPS-induced ALI in mice and in RAW264.7 cells. Thus, plantamajoside may be a potential therapy for the treatment of pulmonary inflammation.

  9. Liver function tests in acute hepatitis in children

    Directory of Open Access Journals (Sweden)

    Shweta

    2016-08-01

    Conclusions: This study helps us to analyze the incidence of HBsAg positive cases presenting with clinical features of acute hepatitis and degree of alteration of liver functions would help the physician in better management of the cases. [Int J Res Med Sci 2016; 4(8.000: 3184-3187

  10. [Change in pancreatic exocrine function in acute appendicitis].

    Science.gov (United States)

    Ivanov, Iu A

    1979-10-01

    In order to study changes in the functional state of the pancreas 1572 investigations of the blood and urine amylase, atoxylresistant lipase of the blood serum before operation were performed in different postoperative periods in 131 patients with acute appendicitis. The enzyme activity was established to increase, especially in destructive forms of appendicitis and in elderly patients.

  11. Acute myocardial infarction mimicking squamous cell lung cancer with bone metastases due to hypercalcemia: a case report

    Institute of Scientific and Technical Information of China (English)

    FANG Chong-feng; XU Geng; CHEN Yang-xin

    2010-01-01

    @@ Acute myocardial infarction (AMI), the most severe coronary artery disease, is one of the most frequent cardiac emergencies, and early diagnosis and treatment are very important to decrease the subsequent cardiac adverse events such as malignant arrhythmia and sudden cardiac death. But in fact, lots of diseases are similar to AMI in clinical practice, of which the most common are myocarditis, pulmonary embolism in department of cardiology. Here we report a case of AMI-like squamous cell lung cancer with bone metastases.

  12. Differential diagnosis of acute miliary pulmonary tuberculosis from widespread-metastatic cancer for postoperative lung cancer patients: two cases

    Science.gov (United States)

    Zhao, Wei; Tian, Yuke; Peng, Feng; Long, Jianlin; Liu, Lan; Lu, You

    2017-01-01

    Pulmonary infections and lung cancer can resemble each other on radiographic images, which makes it difficult to diagnosis accurately and apply an appropriate therapy. Here we report two cases that two postoperative patients with lung adenocarcinoma developed diffuse nodules in bilateral lungs in a month which needed to be distinguished between metastatic malignancies and infectious diseases. Although there are much similarities in disease characteristics of two cases, patient in case one was diagnosed as acute miliary pulmonary tuberculosis (TB) while patient in case two was diagnosed as metastatic disease. The symptoms and pulmonary foci on CT scan of patient in case one improved distinctly after the immediate anti-TB treatment, but the disease of patient in case two progressed after chemotherapy. These findings caution us that differential diagnosis is crucial and have significance in guiding clinical work.

  13. Adult Lysophosphatidic Acid Receptor 1-Deficient Rats with Hyperoxia-Induced Neonatal Chronic Lung Disease Are Protected against Lipopolysaccharide-Induced Acute Lung Injury

    Science.gov (United States)

    Chen, Xueyu; Walther, Frans J.; Laghmani, El H.; Hoogeboom, Annemarie M.; Hogen-Esch, Anne C. B.; van Ark, Ingrid; Folkerts, Gert; Wagenaar, Gerry T. M.

    2017-01-01

    Aim: Survivors of neonatal chronic lung disease or bronchopulmonary dysplasia (BPD) suffer from compromised lung function and are at high risk for developing lung injury by multiple insults later in life. Because neonatal lysophosphatidic acid receptor-1 (LPAR1)-deficient rats are protected against hyperoxia-induced lung injury, we hypothesize that LPAR1-deficiency may protect adult survivors of BPD from a second hit response against lipopolysaccharides (LPS)-induced lung injury. Methods: Directly after birth, Wistar control and LPAR1-deficient rat pups were exposed to hyperoxia (90%) for 8 days followed by recovery in room air. After 7 weeks, male rats received either LPS (2 mg kg−1) or 0.9% NaCl by intraperitoneal injection. Alveolar development and lung inflammation were investigated by morphometric analysis, IL-6 production, and mRNA expression of cytokines, chemokines, coagulation factors, and an indicator of oxidative stress. Results: LPAR1-deficient and control rats developed hyperoxia-induced neonatal emphysema, which persisted into adulthood, as demonstrated by alveolar enlargement and decreased vessel density. LPAR1-deficiency protected against LPS-induced lung injury. Adult controls with BPD exhibited an exacerbated response toward LPS with an increased expression of pro-inflammatory mRNAs, whereas LPAR1-deficient rats with BPD were less sensitive to this “second hit” with a decreased pulmonary influx of macrophages and neutrophils, interleukin-6 (IL-6) production, and mRNA expression of IL-6, monocyte chemoattractant protein-1, cytokine-induced neutrophil chemoattractant 1, plasminogen activator inhibitor-1, and tissue factor. Conclusion: LPAR1-deficient rats have increased hyperoxia-induced BPD survival rates and, despite the presence of neonatal emphysema, are less sensitive to an aggravated “second hit” than Wistar controls with BPD. Intervening in LPA-LPAR1-dependent signaling may not only have therapeutic potential for neonatal chronic

  14. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  15. Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Nørgaard, Astrid; Iversen, Martin

    2010-01-01

    expression and acute rejection is still being debated. Some studies have been performed on blood samples from lung-transplanted patients, while others have investigated the local immune response in the lungs by analysing broncho-alveolar-lavage (BAL) fluids or biopsies. Biopsies are considered the gold...

  16. Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury.

    Science.gov (United States)

    Wu, Deqing; Zeng, Yue; Fan, Yuting; Wu, Jianghong; Mulatibieke, Tunike; Ni, Jianbo; Yu, Ge; Wan, Rong; Wang, Xingpeng; Hu, Guoyong

    2016-02-04

    Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM.

  17. Acute lung inflammation in Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice: a comparative study.

    Science.gov (United States)

    Kumar, Vijay; Chhibber, Sanjay

    2011-10-01

    Lungs play an important role in the body's defense against a variety of pathogens, but this network of immune system-mediated defense can be deregulated during acute pulmonary infections. The present study compares acute lung inflammation occurring during Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice. Pneumonia was induced by intranasal instillation of bacteria (10(4) cfu), while sepsis was developed by placing the fibrin-thrombin clot containing known amount of bacteria (10(2) cfu) into the peritoneal cavity of animals. Mice with sepsis showed 100% mortality within five post-infection days, whereas all the animals with pneumonia survived. In animals suffering from K. pneumoniae B5055-induced pneumonia, all the inflammatory parameters (TNF-α, IL-1α, MPO, MDA, and NO) were found to be maximum till third post-infection day, after that, a decline was observed, whereas in septic animals, all the above-mentioned markers of inflammation kept on increasing. Histopathological study showed presence of alternatively activated alveolar macrophages (or foam cells) in lungs of mice with pneumonia after third post-infection day, which might have contributed to the induction of resolution of inflammation, but no such observation was made in lungs of septic mice. Hence, during pneumonia, controlled activation of macrophages may lead to resolution of inflammation.

  18. Effects of continuous tracheal gas insufflation during pressure limited ventilation on pulmonary surfactant in rabbits with acute lung injury

    Institute of Scientific and Technical Information of China (English)

    ZHU Guang-fa; ZHANG Wei; ZONG Hua; LIANG Ying

    2006-01-01

    Background Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (VT) while maintaining constant partial arterial CO2 pressure (PaCO2). We hypothesised that TGI limited peak inspiratory pressure (PIP) and VT and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI).Methods ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n=8 for each group), and subsequently ventilated with limited PIP and VT to maintain PaCO2 within 35 to 45 mmHg for 4 hours. Physiological dead space to VT ratio (VD/VT), dynamic respiratory compliance (Cdyn) and partial arterial O2 pressure (PaO2) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (Vv), myeloperoxidase and interleukin (IL)-8.Results TGI resulted in significant (P<0.05 or P<0.01) decrease in PIP [(22.4±1.8) cmH2O vs (29.5±1.1) cmH2O], VT [(6.9±1.3) ml/kg vs (9.8±1.11) ml/kg], VD/VT [(32±5)% vs (46±2)%], TP [(109±22) mg/kg vs (187±25) mg/kg], SA/LA (2.5±0.4 vs 5.4±0.7), myeloperoxidase [(6.2±0.5) U/g tissue vs (12.3±0.8) U/g tissue] and IL-8 [(987±106) ng/g tissue vs (24±3) mN/m] of BALF, and significant (P<0.05) increase in Cdyn [(0.47±0.02) ml ·cmH2O-1 ·kg-1 vs (0.31±0.02) ml ·cmH2O-1 ·kg-1], PaO2 [(175±24) mmHg vs (135±26) mmHg],TPL/TP (52±8 vs 33±11) and Vv (0.65±0.05 vs 0

  19. Acute and subacute non-infectious lung diseases. Usefulness of HRCT for evaluation of activity especially in follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Johkoh, Takeshi; Tomiyama, Noriyuki; Honda, Osamu [Osaka Univ., Suita (Japan). Medical School] (and others)

    2000-08-01

    The purpose of this study was to survey the usefulness of high-resolution CT (HRCT) for the evaluation of activity in acute and subacute non-infectious diffuse infiltrative lung diseases before and after corticosteroid treatment. Sequential HRCT images and chest radiographs obtained before and after treatment were retrospectively evaluated in 33 patients with acute or subacute non-infectious diffuse infiltrative lung diseases. All these patients were histologically confirmed to have pulmonary Inflammation and to have responded to treatment with corticosteroid. Radiographic and CT scores were correlated with the degree of dyspnea and the results of arterial blood gas analysis using Spearman's rank-correlation coefficient. On follow-up HRCT, the profusion score of areas with increased attenuation was significantly correlated with arterial oxygen tension (PaO{sub 2}) (p=.003, r=-.53) and the alveolar-arterial oxygen tension difference (AaDO{sub 2}) (p=.001, r=.57). No other correlation was found after treatment. Nodular and linear opacities were more commonly seen on follow-up chest radiographs and HRCT images than on initial ones. HRCT is useful for the evaluation of disease activity in acute and subacute non-infectious infiltrative lung diseases before and after treatment if paying special attention to the profusion of ground-glass attenuation. Even if pretreatment HRCT has not been performed, posttreatment HRCT should be examined. (author)

  20. Air Pollution, Airway Inflammation, and Lung Function in a Cohort Study of Mexico City Schoolchildren

    Science.gov (United States)

    Barraza-Villarreal, Albino; Sunyer, Jordi; Hernandez-Cadena, Leticia; Escamilla-Nuñez, Maria Consuelo; Sienra-Monge, Juan Jose; Ramírez-Aguilar, Matiana; Cortez-Lugo, Marlene; Holguin, Fernando; Diaz-Sánchez, David; Olin, Anna Carin; Romieu, Isabelle

    2008-01-01

    Background The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. Objective In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. Methods We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (FeNO), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. Results An increase of 17.5 μg/m3 in the 8-hr moving average of PM2.5 levels (interquartile range) was associated with a 1.08-ppb increase in FeNO [95% confidence interval (CI), 1.01–1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98–1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00–1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter < 2.5 μm in aerodynamic diamter (PM2.5) was significantly inversely associated with forced expiratory volume in 1 sec (FEV1) (p = 0.048) and forced vital capacity (FVC) (p = 0.012) in asthmatic children and with FVC (p = 0.021) in nonasthmatic children. FeNO and FEV1 were inversely associated (p = 0.005) in asthmatic children. Conclusions Exposure to PM2.5 resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children. PMID:18560490

  1. Mucoactive effects of naringin in lipopolysaccharide-induced acute lung injury mice and beagle dogs.

    Science.gov (United States)

    Chen, Yan; Wu, Hao; Nie, Yi-chu; Li, Pei-bo; Shen, Jian-gang; Su, Wei-wei

    2014-07-01

    Our previous study has demonstrated that naringin attenuates EGF-induced MUC5AC hypersecretion in A549 cells by suppressing the cooperative activities of MAPKs/AP-1 and IKKs/IκB/NF-κB signaling pathways. However, the volume of airway mucus is determined by two factors including the number of mucous cells and capacity of mucus secretion. The aim of the present study is to explore the mucoactive effects of naringin in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and beagle dogs. The results demonstrated that naringin of 12.4 mg/kg treatment significantly decreased LPS-induced enhancement of sputum volume and pulmonary inflammation, remarkably increased the subglottic sputum volume and solids content in sputum of lower trachea, while partially, but not fully, significantly increased the elasticity and viscosity of sputum in lower trachea of beagle dogs. Moreover, the MUC5AC content in BALF and goblet-cells in large airways of LPS-induced ALI mice were significantly attenuated by dexamethasone (5 mg/kg), ambroxol (25 mg/kg), and naringin (15, 60 mg/kg). However, the goblet-cells hyperplasia in small airways induced by LPS was only significantly inhibited by dexamethasone and naringin (60 mg/kg). In conclusion, naringin exhibits mucoactive effects through multiple targets which including reduction of goblet cells hyperplasia and mucus hypersecretion, as well as promotion of sputum excretion.

  2. A clinical study of multiple trauma combined with acute lung injury

    Institute of Scientific and Technical Information of China (English)

    Tao Liang; Yong-Fu Ma; Jian Zhu; Dao-Xi Wang; Yang Liu

    2016-01-01

    Objective: To study the changes of the contents of inflammatory mediators in serum of polytrauma patients with acute lung injury (ALI) and their correlation with the disease. Methods: Patients suffering from multiple trauma combined with ALI were selected as ALI group (n=54). Patients suffering from multiple trauma without ALI were considered as the control group (n=117). The severity of the disease of patients in the two groups was assessed. Arterial blood was extracted for blood gas analysis. Venous blood was extracted to detect the contents of inflammatory mediators tumor necrosis factor-a, interleukin-1b (IL-1b), IL-10, granulocyte-macrophage colony stimulating factor, NO, endothelin-1. Results: The scores of injury severity score [(25.42 ± 3.58) vs. (17.03 ± 2.25)], systemic inflammatory response syndrome [(3.85 ± 0.52) vs. (2.20 ± 0.36)] and acute physiology and chronic health evaluation II [(92.63 ± 11.04) vs. (60.46 ± 8.87)] in patients in ALI group were all significantly higher than those in the control group and its correcting shock time [(8.39 ± 1.05) vs. (5.15 ± 0.72) h] was longer than that of the control group. The amount of blood transfusion [(674.69 ± 93.52) vs. (402.55 ± 57.65) mL] was greater than that in the control group. The contents of the arterial partial pressure of oxygen [(76.65 ± 9.68) vs. (86.51 ± 10.56) mmHg], arterial blood pressure of carbon dioxide [(27.76 ± 4.82) vs. (36.78 ± 5.82) mmHg] and arterial partial pressure of oxygen/fraction of inspired oxygen [(236.94 ± 36.49) vs. (353.95 ± 47.76)] were all significantly lower than those in the control group. The contents of serum tumor necrosis factor-a, IL-1b, IL-10, granulocyte-macrophage colony stimulating factor, NO and endothelin-1 were obviously higher than those of control group and also positively correlated with the scores of injury severity score, systemic inflammatory response syndrome and acute physiology and chronic health evaluation II.

  3. A clinical study of multiple trauma combined with acute lung injury

    Directory of Open Access Journals (Sweden)

    Tao Liang

    2016-11-01

    Full Text Available Objective: To study the changes of the contents of inflammatory mediators in serum of polytrauma patients with acute lung injury (ALI and their correlation with the disease. Methods: Patients suffering from multiple trauma combined with ALI were selected as ALI group (n = 54. Patients suffering from multiple trauma without ALI were considered as the control group (n = 117. The severity of the disease of patients in the two groups was assessed. Arterial blood was extracted for blood gas analysis. Venous blood was extracted to detect the contents of inflammatory mediators tumor necrosis factor-a, interleukin-1b (IL-1b, IL-10, granulocyte-macrophage colony stimulating factor, NO, endothelin-1. Results: The scores of injury severity score [(25.42 ± 3.58 vs. (17.03 ± 2.25], systemic inflammatory response syndrome [(3.85 ± 0.52 vs. (2.20 ± 0.36] and acute physiology and chronic health evaluation II [(92.63 ± 11.04 vs. (60.46 ± 8.87] in patients in ALI group were all significantly higher than those in the control group and its correcting shock time [(8.39 ± 1.05 vs. (5.15 ± 0.72 h] was longer than that of the control group. The amount of blood transfusion [(674.69 ± 93.52 vs. (402.55 ± 57.65 mL] was greater than that in the control group. The contents of the arterial partial pressure of oxygen [(76.65 ± 9.68 vs. (86.51 ± 10.56 mmHg], arterial blood pressure of carbon dioxide [(27.76 ± 4.82 vs. (36.78 ± 5.82 mmHg] and arterial partial pressure of oxygen/fraction of inspired oxygen [(236.94 ± 36.49 vs. (353.95 ± 47.76] were all significantly lower than those in the control group. The contents of serum tumor necrosis factor-a, IL-1b, IL- 10, granulocyte-macrophage colony stimulating factor, NO and endothelin-1 were obviously higher than those of control group and also positively correlated with the scores of injury severity score, systemic inflammatory response syndrome and acute physiology and chronic health evaluation II. Conclusions

  4. Lung Function Measurement with Multiple-Breath-Helium Washout System

    CERN Document Server

    Wang, Jau-Yi; Owers-Bradley, John; Mellor, Chris

    2011-01-01

    Multiple-breath-washout (MBW) measurements are regarded as a sensitive technique which can reflect the ventilation inhomogeneity of respiratory airways. Typically nitrogen is used as the tracer gas and is washed out by pure oxygen in multi-breath-nitrogen (MBNW) washout tests. In this work, instead of using nitrogen, helium is used as the tracer gas and a multiple-helium-breath-washout (MBHW) system has been developed for the lung function study. A commercial quartz tuning fork with a resonance frequency of 32768 Hz has been used for detecting the change of the respiratory gas density. The resonance frequency of the tuning fork decreases linearly with increasing density of the surrounding gas. Knowing the CO2 concentration from the infrared carbon dioxide detector, the helium concentration can be determined. Results from 12 volunteers (3 mild asthmatics, 2 smokers, 1 with asthma history, 1 with COPD history, 5 normal) have shown that mild asthmatics have higher ventilation inhomogeneity in either conducting o...

  5. The Effects of Dexamethasone and L-NAME on Acute Lung Injury in Rats with Lung Contusion.

    Science.gov (United States)

    Kozan, Ahmet; Kilic, Nermin; Alacam, Hasan; Guzel, Ahmet; Guvenc, Tolga; Acikgoz, Mehmet

    2016-10-01

    The therapeutic efficiency of an anti-inflammatory agent, dexamethasone (DXM), and a nitric oxide synthase (NOS) inhibitor, Nitro-L-arginine methyl ester (L-NAME), in lung tissue injury after lung contusion was investigated. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), YKL-40, an inflammatory peptide, inducible NOS (iNOS), and Clara cell protein 16 (CC-16) were evaluated. Immunohistochemical analyses were also performed, and the lung tissue was examined histopathologically. The study consisted of eight groups of Sprague-Dawley rats (n = 10 in each group), weighing 250-300 g: (1) control, (2) contusion, (3) control + DXM, (4) contusion + DXM, (5) control + L-NAME (6) contusion + L-NAME, (7) control + DXM + L-NAME, and (8) contusion + DXM + L-NAME. A previously developed lung contusion model was used, in addition to the control group. The rats were administered DXM and L-NAME intraperitoneally (i.p.) at doses of 15 and 60 mg/kg/day, respectively. DXM and L-NAME administration decreased the iNOS level in the contusion groups. DXM increased the levels of YKL-40 and IL-10 in both the control and contusion groups, with higher levels in the contusion groups. L-NAME increased the serum level of IL-10 in the lung contusion groups. DXM increased the synthesis of CC-16 in the control and contusion groups. The combined use of a high-dose steroid and NOS inhibitor resulted in the death of the rats. Steroids can increase the level of cytokines, such as YKL-40 and IL-10, and the synthesis of CC-16 and prevent pneumonia, ALI/ARDS, and sepsis in lung contusion.

  6. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

    Science.gov (United States)

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-06-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P transplantation was higher (79 [40-84] vs. 39 [36-46], P transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).

  7. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    T N Hagawane

    2016-01-01

    Results: It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6 levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. Interpretation & conclusions: The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

  8. GST-omega genes interact with environmental tobacco smoke on adult level of lung function

    NARCIS (Netherlands)

    de Jong, Kim; Boezen, Hendrika; ten Hacken, Nicolaas; Postma, Dirkje S; Vonk, Judith M

    2013-01-01

    BACKGROUND: Lung growth in utero and lung function loss during adulthood can be affected by exposure to environmental tobacco smoke (ETS). The underlying mechanisms have not been fully elucidated. Both ETS exposure and single nucleotide polymorphisms (SNPs) in Glutathione S-Transferase (GST) Omega g

  9. Proton magnetic resonance imaging for assessment of lung function and respiratory dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Eichinger, Monika [Deutsches Krebsforschungszentrum (DKFZ), Department of Radiology (E010), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: m.eichinger@dkfz.de; Tetzlaff, Ralf; Puderbach, Michael [Deutsches Krebsforschungszentrum (DKFZ), Department of Radiology (E010), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Woodhouse, Neil [Unit of Academic Radiology, University of Sheffield (United Kingdom); Kauczor, H.-U. [Deutsches Krebsforschungszentrum (DKFZ), Department of Radiology (E010), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2007-12-15

    Since many pulmonary diseases present with a variable regional involvement, modalities for assessment of regional lung function gained increasing attention over the last years. Together with lung perfusion and gas exchange, ventilation, as a result of the interaction of the respiratory pump and the lungs, is an indispensable component of lung function. So far, this complex mechanism is still mainly assessed indirectly and globally. A differentiation between the individual determining factors of ventilation would be crucial for precise diagnostics and adequate treatment. By dynamic imaging of the respiratory pump, the mechanical components of ventilation can be assessed regionally. Amongst imaging modalities applicable to this topic, magnetic resonance imaging (MRI), as a tool not relying on ionising radiation, is the most attractive. Recent advances in MRI technology have made it possible to assess diaphragmatic and chest wall motion, static and dynamic lung volumes, as well as regional lung function. Even though existing studies show large heterogeneity in design and applied methods, it becomes evident that MRI is capable to visualise pulmonary function as well as diaphragmatic and thoracic wall movement, providing new insights into lung physiology. Partly contradictory results and conclusions are most likely caused by technical limitations, limited number of studies and small sample size. Existing studies mainly evaluate possible imaging techniques and concentrate on normal physiology. The few studies in patients with lung cancer and emphysema already give a promising outlook for these techniques from which an increasing impact on improved and quantitative disease characterization as well as better patient management can be expected.

  10. Dietary factors and lung function in the general population : wine and resveratrol intake

    NARCIS (Netherlands)

    Siedlinski, M; Boer, J M A; Smit, H A; Postma, D S; Boezen, H M

    2012-01-01

    Wine intake is associated with a better lung function in the general population, yet the source of this effect is unknown. Resveratrol, a polyphenol in wine, has anti-inflammatory properties in the lung, its effects being partially mediated via induction of Sirtuin (SIRT) 1 activity. We assessed the

  11. The effect of pulsatile cardiopulmonary bypass on lung function in elderly patients

    NARCIS (Netherlands)

    Engels, Gerwin E.; Dodonov, Mikhail; Rakhorst, Gerhard; van Oeveren, Willem; Milano, Aldo D.; Gu, Y. John; Faggian, Giuseppe

    2014-01-01

    Purpose: Cardiopulmonary bypass is still a major cause of lung injury and delay in pulmonary recovery after cardiac surgery. Although it has been shown that pulsatile flow induced by intra-aortic balloon pumping is beneficial for preserving lung function, it is not clear if the same beneficial effec

  12. No relationship between lung function and high-sensitive C-reactive protein in adolescence

    DEFF Research Database (Denmark)

    Nybo, Mads; Hansen, Henrik Steen; Siersted, Hans Christian

    2010-01-01

      Several studies on adults have indicated that lower spirometric lung function may be associated with increased systemic inflammation, but no studies have investigated if this association is already present in adolescence. Objective:  We explored the temporal relationship between changes in lung...

  13. Molecular mechanisms underlying variations in lung function : a systems genetics analysis

    NARCIS (Netherlands)

    Obeidat, Ma'en; Hao, Ke; Bosse, Yohan; Nickle, David C.; Nie, Yunlong; Postma, Dirkje S.; Laviolette, Michel; Sandford, Andrew J.; Daley, Denise D.; Hogg, James C.; Elliott, W. Mark; Fishbane, Nick; Timens, Wim; Hysi, Pirro G.; Kaprio, Jaakko; Wilson, James F.; Hui, Jennie; Rawal, Rajesh; Schulz, Holger; Stubbe, Beate; Hayward, Caroline; Polasek, Ozren; Jarvelin, Marjo-Riitta; Zhao, Jing Hua; Jarvis, Deborah; Kahonen, Mika; Franceschini, Nora; North, Kari E.; Loth, Daan W.; Brusselle, Guy G.; Smith, Albert Vernon; Gudnason, Vilmundur; Bartz, Traci M.; Wilk, Jemma B.; O'Connor, George T.; Cassano, Patricia A.; Tang, Wenbo; Wain, Louise V.; Artigas, Maria Soler; Gharib, Sina A.; Strachan, David P.; Sin, Don D.; Tobin, Martin D.; London, Stephanie J.; Hall, Ian P.; Pare, Peter D.

    2015-01-01

    Background Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume

  14. Regulation on the expression of Clara cell secretory protein in the lungs of the rats with acute lung injury by growth hormone

    Institute of Scientific and Technical Information of China (English)

    MIN Jia; LUO Fo-quan; ZHAO Wei-lu

    2012-01-01

    Background Clara cell secretory protein (CC16) is an important lung derived protective factor and may play an important role on the pathogenesis of acute lung injury (ALl) induced by endotoxemia.Growth hormone (GH) is an important anabolism hormone secreted by GH cells of the hypophysis.Pravious research showed that GH would significantly exacerbate ALl induced by endotoxemia,but the mechanism is not very clear yet.Whether the effects are related to CC16 or not is undetermined.Methods One hundred and twelve male Sprague-Dawley rats were randomly divided into an ALl group and a GH group.The rats in the two groups were subdivided into seven subgroups,according to injection with lipopolysaccharides (LPS) or not,then according to different intervals of time after LPS injection; 0 hour (pre-injection of LPS,acted as control group),0.5 hour,1 hour,2 hours,4 hours,6 hours and 24 hours for subgroups.Pulmonary alveolar septa area density (PASAD) and ploymorphonuclear cells (PMN) in the lungs were analyzed morphometrically.The levels of tumor necrosis factor (TNF) and interleukin 6 (1L-6) were determined by radioimmunoassay.To analyze the expression and activation of nuclear factor kappa B (NF-kB),the numbers of NF-kB positive cells in lungs were counted after immunofluorescence staining.and the levels of NF-KB inhibitory protein-α (1KB-α) in lung homogenates of rats were detected by Western blotting.The expression levels of CC16 mRNA in lungs of the rats with ALl were determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).The levels of CC16 protein in lung homogenates were detected by Western blotting.Results Half an hour after LPS injury both the PASAD and PMN numbers in lungs of the rats with ALl began to increase significantly and peaked at 6-hour post-injury.They then began to recover and reached normal levels at 24-hour post-injury.Both the PASAD and PMN numbers in the GH group increased more significantly than those in the ALl group

  15. High blood pressure, antihypertensive medication and lung function in a general adult population

    Directory of Open Access Journals (Sweden)

    Meisinger Christa

    2011-04-01

    Full Text Available Abstract Background Several studies showed that blood pressure and lung function are associated. Additionally, a potential effect of antihypertensive medication, especially beta-blockers, on lung function has been discussed. However, side effects of beta-blockers have been investigated mainly in patients with already reduced lung function. Thus, aim of this analysis is to determine whether hypertension and antihypertensive medication have an adverse effect on lung function in a general adult population. Methods Within the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function tests and blood pressure measurements. Additionally, information on anthropometric measurements, medical history and use of antihypertensive medication was available. Multivariable regression models were applied to study the association between blood pressure, antihypertensive medication and lung function. Results High blood pressure as well as antihypertensive medication were associated with lower forced expiratory volume in one second (p = 0.02 respectively p = 0.05; R2: 0.65 and forced vital capacity values (p = 0.01 respectively p = 0.05, R2: 0.73. Furthermore, a detailed analysis of antihypertensive medication pointed out that only the use of beta-blockers was associated with reduced lung function, whereas other antihypertensive medication had no effect on lung function. The adverse effect of beta-blockers was significant for forced vital capacity (p = 0.04; R2: 0.65, while the association with forced expiratory volume in one second showed a trend toward significance (p = 0.07; R2: 0.73. In the same model high blood pressure was associated with reduced forced vital capacity (p = 0.01 and forced expiratory volume in one second (p = 0.03 values, too. Conclusion Our analysis indicates that both high blood pressure and the use of beta-blockers, but not the use of other antihypertensive medication, are associated with reduced lung function in a

  16. [Humidifier lung].

    Science.gov (United States)

    Gerber, P; de Haller, R; Pyrozynski, W J; Sturzenegger, E R; Brändli, O

    1981-02-07

    Breathing air from a humidifier or an air conditioning unit contaminated by various microorganisms can cause an acute lung disease involving fever, cough and dyspnea, termed "humidifier fever". This type of hypersensitivity pneumonitis was first described in 1959 by PESTALOZZI in the Swiss literature and subsequently by BANASZAK et al. in the Anglo-American. Here a chronic form of this disease which led to pulmonary fibrosis is described: A 37-year-old woman who works in a cheese shop presented with dyspnea which had been progressive over two years, weight loss, a diffuse reticular pattern radiographically and a severe restrictive defect in lung function tests. Open lung biopsy revealed chronic interstitial and alveolar inflammation with non-caseating granulomas and fibrotic changes. Circulating immune complexes and precipitins against the contaminated humidifier water and cheese mites were found, but no antibodies suggesting legionnaires' disease. Two out of five otherwise healthy employees of this cheese shop, where a new humidifying system had been installed 7 years earlier, also had precipitins against the contaminated water from the humidifier and the cheese mites. Despite ending of exposure and longterm steroid and immunosuppressive therapy, the signs and symptoms of pulmonary fibrosis persisted. Contrary to the acute disease, this chronic form is termed "humidifier lung". The importance is stressed of investigating the possibility of exposure to contaminated humidifiers or air conditioning units in all cases of newly detected pulmonary fibrosis.

  17. 15-deoxy-△12,14-prostaglandin J2 ameliorates endotoxin-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liu Dong; Geng Zhilong; Zhu Wankun; Wang Huiwen; Chen Ye; Liang Juan

    2014-01-01

    Background A proinflammatory milieu emerging in the lung due to neutrophil accumulation and activation is a key in the pathogenesis of acute lung injury (ALI).15-deoxy-△12,14-prostaglandin J2 (15d-PGJ2),one of the terminal products of the cyclooxygenase-2 pathway,is known to be the endogenous ligand of peroxisome proliferator-activated receptor y (PPAR-y) with multiple physiological properties.Growing evidence indicates that 15d-PGJ2 has anti-inflammatory,antiproliferative,cytoprotective and pro-resolving effects.We investigated whether 15d-PGJ2 has a protective effect against endotoxin-induced acute lung injury in rats.Methods Twenty-four male Wistar rats were randomly assigned into four groups (n=6 per group):sham+vehicle group,sham+15d-PGJ2 group,LPS+vehicle group,and LPS+15d-PGJ2 group.The rats were given either lipopolysaccharide (LPS,6 mg/kg intravenously) or saline,and pretreated with 15d-PGJ2 (0.3 mg/kg intravenously) or its vehicle (dimethyl sulphoxide) 30 minutes before LPS.Histological alterations,wet/dry weight (W/D) ratio and myeloperoxidase (MPO) activity as well as tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels were determined in lung tissues four hours after LPS injection.Immunohistochemical analysis for intercellular adhesion molecule-1 (ICAM-1) expression and Western blotting analysis for nuclear factor (NF)-κB p65 translocation and IκBα protein levels were also studied.Results 15d-PGJ2 pretreatment significantly attenuated LPS-induced lung injury,and reduced the increased W/D ratio,MPO activity,TNF-α,CINC-1 levels,and ICAM-1 expression in the lung.15d-PGJ2 also suppressed the nuclear NF-ΚB p65 translocation and increased cytosolic IKBα levels.Conclusions 15d-PGJ2 protects against endotoxin-induced acute lung injury,most likely through the reduction of proinflammatory protein levels during endotoxemia subsequent to the inhibition of NF-ΚB activation.

  18. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    Energy Technology Data Exchange (ETDEWEB)

    MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O' Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B. T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-06-04

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  19. Neonates with reduced neonatal lung function have systemic low-grade inflammation

    DEFF Research Database (Denmark)

    Chawes, Bo L.K.; Stokholm, Jakob; Bønnelykke, Klaus;

    2015-01-01

    Background: Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced...... lung function. ObjectiveWe sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation.  Methods: Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children...

  20. Gender difference in smoking effects on lung function and risk of hospitalization for COPD

    DEFF Research Database (Denmark)

    Prescott, E; Bjerg, A M; Andersen, P K;

    1997-01-01

    Recent findings suggest that females may be more susceptible than males to the deleterious influence of tobacco smoking in developing chronic obstructive pulmonary disease (COPD). This paper studies the interaction of gender and smoking on development of COPD as assessed by lung function...... greater impact on the lung function of females than males, and after adjusting for smoking females subsequently suffered a higher risk of being admitted to hospital for COPD. Results suggest that adverse effects of smoking on lung function may be greater in females than in males....

  1. Relationship between body balance, lung function, nutritional status and functional capacity in adults with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Jennifer T. S. Penafortes

    2013-10-01

    Full Text Available BACKGROUND: Cystic fibrosis (CF is a hereditary condition in which lung disease affects all patients. In addition to pulmonary involvement, the multisystemic components of CF cause significant physical limitations. However, the impact of lung function on balance control in CF has not been studied. OBJECTIVE: To assess body balance in adults with CF and to test its possible associations with lung function, nutritional status, and functional capacity. METHOD: This was a cross-sectional study in which 14 adults with CF underwent pulmonary function testing (spirometry, body plethysmography, and carbon monoxide diffusing capacity (DLco, respiratory muscle strength, 6-min walking distance (6MWD, Berg balance scale (BBS, nutritional analysis (body mass index and bioelectrical impedance, and stabilometry. Body balance was quantified using stabilometry; all participants performed the following two trials: opened base, eyes open (OBEO; closed base, eyes closed (CBEC. RESULTS: In stabilometry, the median for the lateral range and anterior-posterior range in the CBEC trial was 0.10 (0.08-0.11 and 0.13 (0.11-0.22, respectively (p<0.05. The maximal inspiratory pressure (MIP correlated inversely with the lateral standard deviation (ρ=–0.61; p<0.05 as the DLco correlated positively with the anterior-posterior range (ρ=0.54; p<0.05. There were significant relationships between body composition indexes and almost all stabilometric variables measured. There were no relationships of the BBS and 6MWD with the stabilometric variables. CONCLUSIONS: In adults with CF, imbalance occurs mainly in the anterior-posterior direction and is especially associated with body composition.

  2. Therapeutic effect of intravenous infusion of perfluorocarbon emulsion on LPS-induced acute lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Shike Hou

    Full Text Available Acute lung injury (ALI and its more severe form, acute respiratory distress syndrome (ARDS are the leading causes of death in critical care. Despite extensive efforts in research and clinical medicine, mortality remains high in these diseases. Perfluorocarbon (PFC, a chemical compound known as liquid ventilation medium, is capable of dissolving large amounts of physiologically important gases (mainly oxygen and carbon dioxide. In this study we aimed to investigate the effect of intravenous infusion of PFC emulsion on lipopolysaccharide (LPS induced ALI in rats and elucidate its mechanism of action. Forty two Wistar rats were randomly divided into three groups: 6 rats were treated with saline solution by intratracheal instillation (control group, 18 rats were treated with LPS by intratracheal instillation (LPS group and the other 18 rats received PFC through femoral vein prior to LPS instillation (LPS+PFC group. The rats in the control group were sacrificed 6 hours later after saline instillation. At 2, 4 and 6 hours of exposure to LPS, 6 rats in the LPS group and 6 rats in LPS+PFC group were sacrificed at each time point. By analyzing pulmonary pathology, partial pressure of oxygen in the blood (PaO2 and lung wet-dry weight ratio (W/D of each rat, we found that intravenous infusion of PFC significantly alleviated acute lung injury induced by LPS. Moreover, we showed that the expression of pulmonary myeloperoxidase (MPO, intercellular adhesion molecule-1 (ICAM-1 of endothelial cells and CD11b of polymorphonuclear neutrophils (PMN induced by LPS were significantly decreased by PFC treatment in vivo. Our results indicate that intravenous infusion of PFC inhibits the infiltration of PMNs into lung tissue, which has been shown as the core pathogenesis of ALI/ARDS. Thus, our study provides a theoretical foundation for using intravenous infusion of PFC to prevent and treat ALI/ARDS in clinical practice.

  3. Therapeutic effect of intravenous infusion of perfluorocarbon emulsion on LPS-induced acute lung injury in rats.

    Science.gov (United States)

    Hou, Shike; Ding, Hui; Lv, Qi; Yin, Xiaofeng; Song, Jianqi; Landén, Ning Xu; Fan, Haojun

    2014-01-01

    Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are the leading causes of death in critical care. Despite extensive efforts in research and clinical medicine, mortality remains high in these diseases. Perfluorocarbon (PFC), a chemical compound known as liquid ventilation medium, is capable of dissolving large amounts of physiologically important gases (mainly oxygen and carbon dioxide). In this study we aimed to investigate the effect of intravenous infusion of PFC emulsion on lipopolysaccharide (LPS) induced ALI in rats and elucidate its mechanism of action. Forty two Wistar rats were randomly divided into three groups: 6 rats were treated with saline solution by intratracheal instillation (control group), 18 rats were treated with LPS by intratracheal instillation (LPS group) and the other 18 rats received PFC through femoral vein prior to LPS instillation (LPS+PFC group). The rats in the control group were sacrificed 6 hours later after saline instillation. At 2, 4 and 6 hours of exposure to LPS, 6 rats in the LPS group and 6 rats in LPS+PFC group were sacrificed at each time point. By analyzing pulmonary pathology, partial pressure of oxygen in the blood (PaO2) and lung wet-dry weight ratio (W/D) of each rat, we found that intravenous infusion of PFC significantly alleviated acute lung injury induced by LPS. Moreover, we showed that the expression of pulmonary myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD11b of polymorphonuclear neutrophils (PMN) induced by LPS were significantly decreased by PFC treatment in vivo. Our results indicate that intravenous infusion of PFC inhibits the infiltration of PMNs into lung tissue, which has been shown as the core pathogenesis of ALI/ARDS. Thus, our study provides a theoretical foundation for using intravenous infusion of PFC to prevent and treat ALI/ARDS in clinical practice.

  4. Lung function and risk of fatal and non-fatal stroke. The Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Truelsen, T; Prescott, E; Lange, P;

    2001-01-01

    adjustment for potential confounders: sex, age, smoking, inhalation, body mass index, systolic blood pressure, triglycerides, physical activity in leisure time, education, diabetes mellitus, and antihypertensive treatment. RESULTS: We found an inverse association between FEV1 and risk of first-time stroke....... For each 10% decrease in FEV1 in percentage of expected, the relative risk (RR) increased 1.05 (95% CI : 1.00-1.09, P = 0.03). This represents an approximately 30% higher risk of stroke in the group of people with the lowest lung function as compared to the group with the highest lung function...... function groups. CONCLUSIONS: This study shows that reduced lung function measured in percentage of predicted FEV1 is a predictor of first-time stroke and fatal stroke independent of smoking and inhalation. The high risk of fatal first-ever stroke in the group of people with low lung function may...

  5. Lung function status of workers exposed to wood dust in timber markets in Calabar, Nigeria.

    Science.gov (United States)

    Okwari, O O; Antai, A B; Owu, D U; Peters, E J; Osim, E E

    2005-06-01

    The effect of chronic exposure to dust from local woods such as ebony, achi, and iroko on lung function of timber market workers in Calabar - Nigeria, was studied. Forced vital capacity (FVC), Forced Expiratory Volume in one second, (FEV1), Forced Expiratory Volume as a percentage of forced vital capacity (FEV1 %), and Peak Expiratory Flow Rate (PEFR) were measured in 221 workers (aged 20-25 years) exposed to wood dust to assess their lung function and compared with 200 age- and sex- matched control subjects who were not exposed to any known air pollutant. The concentration of respirable dust was significantly higher in the test (Pwood dust had restrictive pattern of ventilatory function impairment. The lung function indices of the timber workers decreased with their length of service. Chronic exposure to wood dust impairs lung function.

  6. Molecular mechanisms underlying variations in lung function: a systems genetics analysis

    Science.gov (United States)

    Obeidat, Ma’en; Hao, Ke; Bossé, Yohan; Nickle, David C; Nie, Yunlong; Postma, Dirkje S; Laviolette, Michel; Sandford, Andrew J; Daley, Denise D; Hogg, James C; Elliott, W Mark; Fishbane, Nick; Timens, Wim; Hysi, Pirro G; Kaprio, Jaakko; Wilson, James F; Hui, Jennie; Rawal, Rajesh; Schulz, Holger; Stubbe, Beate; Hayward, Caroline; Polasek, Ozren; Järvelin, Marjo-Riitta; Zhao, Jing Hua; Jarvis, Deborah; Kähönen, Mika; Franceschini, Nora; North, Kari E; Loth, Daan W; Brusselle, Guy G; Smith, Albert Vernon; Gudnason, Vilmundur; Bartz, Traci M; Wilk, Jemma B; O’Connor, George T; Cassano, Patricia A; Tang, Wenbo; Wain, Louise V; Artigas, María Soler; Gharib, Sina A; Strachan, David P; Sin, Don D; Tobin, Martin D; London, Stephanie J; Hall, Ian P; Paré, Peter D

    2016-01-01

    Summary Background Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC) in the general population. The lung expression quantitative trait loci (eQTLs) study mapped the genetic architecture of gene expression in lung tissue from 1111 individuals. We used a systems genetics approach to identify single nucleotide polymorphisms (SNPs) associated with lung function that act as eQTLs and change the level of expression of their target genes in lung tissue; termed eSNPs. Methods The SpiroMeta-CHARGE GWAS results were integrated with lung eQTLs to map eSNPs and the genes and pathways underlying the associations in lung tissue. For comparison, a similar analysis was done in peripheral blood. The lung mRNA expression levels of the eSNP-regulated genes were tested for associations with lung function measures in 727 individuals. Additional analyses identified the pleiotropic effects of eSNPs from the published GWAS catalogue, and mapped enrichment in regulatory regions from the ENCODE project. Finally, the Connectivity Map database was used to identify potential therapeutics in silico that could reverse the COPD lung tissue gene signature. Findings SNPs associated with lung function measures were more likely to be eQTLs and vice versa. The integration mapped the specific genes underlying the GWAS signals in lung tissue. The eSNP-regulated genes were enriched for developmental and inflammatory pathways; by comparison, SNPs associated with lung function that were eQTLs in blood, but not in lung, were only involved in inflammatory pathways. Lung function eSNPs were enriched for regulatory elements and were over-represented among genes showing differential expression during

  7. The correlation between lung sound distribution and pulmonary function in COPD patients.

    Directory of Open Access Journals (Sweden)

    Masamichi Mineshita

    Full Text Available BACKGROUND: Regional lung sound intensity in chronic obstructive pulmonary disease (COPD patients is influenced by the severity and distribution of emphysema, obstructed peripheral airways, and altered ribcage and diaphragm configurations and movements due to hyperinflation. Changes in the lung sound distribution accompanied by pulmonary function improvements in COPD patients were observed after bronchodilator inhalation. We investigated the association of lung sound distribution with pulmonary functions, and the effects of emphysematous lesions on this association. These studies were designed to acquire the basic knowledge necessary for the application of lung sound analysis in the physiological evaluation of COPD patients. METHODS: Pulmonary function tests and the percentage of upper- and lower-lung sound intensity (quantitative lung data [QLD] were evaluated in 47 stable male COPD patients (54 - 82 years of age. In 39 patients, computed tomography taken within 6 months of the study was available and analyzed. RESULTS: The ratio of lower QLD to upper QLD showed significant positive correlations with FEV1 %predicted (%FEV1; ρ=0.45, p40%, n=20 and were stronger in less emphysematous patients (n=19, %FEV1; ρ=0.64, p<0.005, %MEF50; ρ=0.71, p<0.001. CONCLUSIONS: In COPD patients, the ratio of lower- to upper-lung sound intensities decreased according to the severity of obstructive changes, although emphysematous lesions considerably affected lung sound distribution.

  8. 丙酮酸乙酯联合乌司他丁对大鼠重症急性胰腺炎肺损伤的保护作用%Potective function of ethyl pyruvate combined with ulinastain on lung injury associated with severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    仲晨; 向俊峰; 刘帅; 杨恒; 苏龙丰; 周蒙滔; 朱耶凡; 曾其强; 张启瑜

    2011-01-01

    目的 观察丙酮酸乙酯联合乌司他丁对大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)肺损伤的保护作用.方法 50只雄性Sprague-Dawley(SD)大鼠随机分为五组:假手术(sham-operated,S)组、SAP组、丙酮酸乙酯(ethyl pyruvate,EP)组、乌司他T(ulinastain,U)组和丙酮酸乙酯联合乌司他T(EP+U)组.除S组外,其余各组均通过逆行性胰胆管注射5%牛磺胆酸钠诱导重症急性胰腺炎模型,关腹6 h及12 h后分别处死两时间点的大鼠,酶法检测血清淀粉酶(amylase,AMY)水平,计算肺脏的湿干比重,ELISA法检测肺脏中的高迁移率蛋白-1(high mobility group Box1,HMGB-1)、肿瘤坏死因子-α(tumor necrosis factor α,TNF-α),观察胰腺和肺脏组织的形态学改变.结果 (1)SAP组大鼠肺脏表现典型的病理变化,包括肺组织间质水肿,肺泡壁增厚,肺大泡或形成局灶性肺不张.EP、U单用或联合均可减轻SAP肺的炎症反应;(2)SAP组血清AMY、肺湿干比均高于相同时间点其他各组水平(P<0.05);(3)SAP组,6 h肺组织TNF-α水平较12 h高,12 h HMGB-1水平较6 h高;(4)EP+U组肺组织HMGB-1水平均较相同时间点EP及U组低(P<0.05).结论 (1)TNF-α仅及HMGB-1均参与大鼠重症急性胰腺炎肺损伤的过程;(2)丙酮酸乙酯、乌司他丁都能减轻SAP肺损伤,联合用药作用更好.%Objective To observe protective of ethyl pyruvate combined with ulinastain on lung injury associated with severe acute pancreatitis (SAP). Methods Fifty male Sprague-Dawley rats were randomly divided into five groups: sham-operated (S) group, SAP group, ethyl pyruvate (EP) group, ulinastain (U) group and ethyl pyruvate+ulinastain (EP+U) group. The SAP rat model was induced by retrograde injection of 5% sodium taurocholate into pancreatic bile duct except for group S. Samples of blood and tissues were collected 6 h and 12 h after the operation. The serum amylase was measured with enzymatic method, lung wet-to-dry-weight (W/ D) ratios was

  9. Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury in Mouse Model.

    Directory of Open Access Journals (Sweden)

    Xing Chen

    Full Text Available To investigate the protective role of the sonic hedgehog (SHH signaling associated with a lipopolysaccharide (LPS-induced acute lung injury (ALI in a mouse model.Male BALB/c mice were randomly divided into four groups: control, LPS, LPS-cyclopamine group and cyclopamine group. ALI was induced by LPS ip injection (5 mg/kg. The sonic hedgehog inhibitor cyclopamine (50 mg/kg was given to the LPS-cyclopamine group at 30 min after LPS injection as well as normal mice as control. Lung injury was observed histologically in hematoxylin and eosin (HE stained tissue sections, semi-quantified by lung tissue injury score, and the lung tissue mass alteration was measured by wet to dry weight ratio (W/D. mRNA expression levels of TNF-α, SHH, Patched (PTC and GLI1 in lung tissue were studied with real time quantitative PCR (RT-PCR, while the protein expression of SHH and GLI1 was determined by western blot analysis.Lung tissue injury score, thickness of alveolar septa, W/D, and TNF-α mRNA expression levels were significantly higher in the ALI mice than the normal mice (P<0.05. The mRNA expression levels of SHH, PTC, and GLI1 in the ALI mice were significantly higher at 12h and 24h after LPS injection, but not at the 6h time point. Protein production of SHH and GLI1 at 6h, 12h, and 24h in the lungs of ALI mice significantly increased, in a time-dependent manner, compared with that in normal mice. Cyclopamine alone has no effect on pathological changes in normal mice. Intervention with cyclopamine in ALI mice led to a reduction in mRNA levels of SHH, PTC, and GLI1 as well as SHH and GLI1 protein levels; meanwhile, the pathological injury scores of lung tissues, thickness of alveolar septa, W/D, and mRNA expression levels of TNF-α increased compared with mice receiving LPS only.The SHH signaling pathway was activated in response to LPS-induced ALI, and up-regulation of SHH expression could alleviate lung injury and be involved in the repair of injured lung

  10. Functional rehabilitation of patients with acute Achilles tendon rupture

    DEFF Research Database (Denmark)

    Mark-Christensen, Troels; Troelsen, Anders; Kallemose, Thomas

    2014-01-01

    . RESULTS: Re-rupture rate, other complications, strength, range of motion, duration of sick leave, return to sport and patient satisfaction were examined. There were no statistically significant differences between groups. A trend favoring functional rehabilitation was seen regarding the examined outcomes....... CONCLUSION: Functional rehabilitation after acute Achilles tendon rupture does not increase the rate of re-rupture or other complications. A trend toward earlier return to work and sport, and increased patient satisfaction was found when functional rehabilitation was used. The present literature is of low...

  11. Video-Assisted versus Open Lobectomy in Patients with Compromised Lung Function: A Literature Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Ruoyu Zhang

    Full Text Available It has been suggested that video-assisted (VATS lobectomy is safer than open lobectomy in patients with compromised lung function, but data regarding this are limited. We assessed acute outcomes of VATS compared to open lobectomy in these high-risk patients using a systematic literature review and meta-analysis of data.The databases PubMed and Scopus were searched for studies published between 2000 and 2013 that reported mortality and morbidity of VATS in high-risk lung cancer patients defined as having compromised pulmonary or cardiopulmonary function. Study selection, data collection and critical assessment of the included studies were performed according to the recommendations of the Cochrane Collaboration.Three case-control studies and three case series that included 330 VATS and 257 open patients were identified for inclusion. Operative mortality, overall morbidity and pulmonary morbidity were 2.5%, 39.3%, 26.2% in VATS patients and 7.8%, 57.5%, 45.5% in open lobectomy group, respectively. VATS lobectomy patients experienced significantly lower pulmonary morbidity (RR = 0.45; 95% CI, 0.30 to 0.67; p = 0.0001, somewhat reduced operative mortality (RR = 0.51; 95% CI, 0.24 to 1.06; p = 0.07, but no significant difference in overall morbidity (RR = 0.68; 95% CI, 0.41 to 1.14; p = 0.14.The existing data suggest that VATS lobectomy is associated with lower risk for pulmonary morbidity compared with open lobectomy in lung cancer patients with compromised lung function.

  12. PAMAM Nanoparticles Promote Acute Lung Injury by Inducing Autophagic Cell Death through the Akt-TSC2-mTOR Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    Chenggang Li; Haolin Liu; Yang Sun; Hongliang Wang; Feng Guo; Shuan Rao; Jiejie Deng; Yanli Zhang; Yufa Miao; Chenying Guo; Jie Meng; Xiping Chen; Limin Li; Dangsheng Li; Haiyan Xu; Heng Wang; Bo Li; Chengyu Jiang

    2009-01-01

    Nanotechnology is an important and emerging industry with a projected annual market of around one trillion US dollars by 2011–2015. Concerns about the toxicity of nanomaterials in humans, however, have recently been raised. Although studies of nanoparticle toxicity have focused on lung disease the molecular link between nanoparticle exposure and lung injury remained unclear. In this report, we show that cationic Starburst polyamidoamine dendrimer (PAMAM), a class of nanomaterials that are being widely developed for clinical applications can induce acute lung injury in vivo. PAMAM triggers autophagic cell death by deregulating the Akt-TSC2-mTOR signaling pathway. The autophagy inhibitor 3-methyladenine rescued PAMAM dendrimer-induced cell death and ameliorated acute lung injury caused by PAMAM in mice. Our data provide a molecular explanation for nanoparticle-induced lung injury, and suggest potential remedies to address the growing concerns of nanotechnology safety.

  13. Surfactant nebulisation : lung function, surfactant distribution and pulmonary blood flow distribution in lung lavaged rabbits

    NARCIS (Netherlands)

    Dijk, Peter H.; Heikamp, A; Bambang Oetomo, Sidarto

    1997-01-01

    Objective: Surfactant nebulisation is a promising alternative to surfactant instillation in newborns with the respiratory distress syndrome. Although less surfactant is deposited in the lung, it improves gas exchange, probably due to a superior distribution. We hypothesize that a more uniform distri

  14. Role of tachykinins in ozone-induced acute lung injury in guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Tepper, J.S.; Costa, D.L.; Fitzgerald, S.; Doerfler, D.L.; Bromberg, P.A. (ManTech Environmental Technology, Inc., Research Triangle Park, NC (United States))

    1993-09-01

    To examine the hypothesis that the acute reversible changes caused by ozone (O3) exposure are mediated by tachykinin release, guinea pigs were depleted of tachykinins by use of repeated capsaicin (CAP) injections before O3 exposure in an attempt to prevent O3-induced functional changes. Unexpectedly, CAP pretreatment caused divergent results in the functional responses to O3. Ventilatory measurements obtained from CAP-pretreated O3-exposed (CAP-O3) animals were exacerbated rather than diminished compared with the effects of O3 alone. Similarly, lavage fluid protein accumulation was enhanced in the CAP-O3 group compared with the O3-exposed group. In better agreement with our initial hypothesis, the CAP-O3 group was less responsive than the O3-exposed animals to histamine aerosol challenge. Additionally, Evans blue dye accumulation, a hallmark of tachykinin release, was increased in O3-exposed animals and was partially blocked in the CAP-O3 group. These data suggest that tachykinin-containing sensory fibers are unlikely to mediate the acute effects of O3 exposure on tidal breathing and lavage fluid protein accumulation but may play a role in causing post-O3 airway hyperreactivity and protein extravasation into the trachea.

  15. Assessment of early acute lung injury in rats exposed to aerosols of consumer products: attempt to disentangle the "Magic Nano" conundrum.

    Science.gov (United States)

    Pauluhn, Jürgen; Hahn, Axel; Spielmann, Horst

    2008-11-01

    In Germany in 2006 a series of rapidly developing and sometimes severe cases of pulmonary health impairment were observed after normal use of the "Magic Nano Glass & Ceramic" spray and "Magic Nano Bath" spray. In contrast, the previously marketed "Magic Nano" pump spray product (handheld trigger device without propellants) was unobtrusive. Analysis of particles discharged from these products did not reveal stable (solid) nano-sized particles. The precipitous increase of pulmonary health impairment in hu