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Sample records for acute lung damage

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

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    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.

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

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    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.

  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.

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    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. Cyclophosphamide in diffuse lung damage.

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    Musiatowicz, B; Sulkowska, M; Sulik, M; Famulski, W; Dziecioł, J; Sobaniec-Lotowska, M; Baltaziak, M; Arciuch, L; Rółkowski, R; Jabłońska, E

    1997-01-01

    Some cyclophosphamide toxic effects on lung tissue are presented. Cyclophosphamide metabolism, pathogenesis of lung damage and morphological lung tissue changes caused by that agent were characterized. Attention was focused on BAL evaluation as a useful method in the monitoring of lung tissue damage degree.

  5. Spores of Aspergillus versicolor isolated from indoor air of a moisture-damaged building provoke acute inflammation in mouse lungs.

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    Jussila, Juha; Komulainen, Hannu; Kosma, Veli-Matti; Nevalainen, Aino; Pelkonen, Jukka; Hirvonen, Maija-Riitta

    2002-12-01

    Microbial growth in moisture-damaged buildings has been associated with respiratory health effects, and the spores of the mycotoxin producing fungus Aspergillus versicolor are frequently present in the indoor air. To characterize the potential of these spores to cause harmful respiratory effects, mice were exposed via intratracheal instillation to a single dose of the spores of A. versicolor (1 x 10(5), 1 x 10(6), 5 x 10(6), 1 x 10(7), or 1 x 10(8) spores), isolated from the indoor air of a moisture-damaged building. Inflammation and toxicity in lungs were evaluated 24 h later by assessment of biochemical markers and histopathology. The time course of the effects was investigated with the dose of 5 x 10(6) spores for up to 28 days. The exposure to the spores increased transiently proinflammatory cytokine levels (tumor necrosis factor [TNF] alpha and interleukin [IL]-6) in bronchoalveolar lavage fluid (BALF). The cytokine responses were dose and time dependent. The highest cytokine concentrations were measured at 6 h after the dose, and they returned to the control level by 3 days. Moreover, the spores of A. versicolor recruited inflammatory cells into airways: Neutrophils peaked transiently at 24 h, macrophages at 3 days, and lymphocytes at 7 days after the dosing. The inflammatory cell response did not completely disappear during the subsequent 28 days, though no histopathological changes were seen at that time point. The spores did not induce expression of inducible nitric oxide synthase in lavaged cells. Only the highest spore dose (1 x 10(8)) markedly increased serum IL-6, increased vascular leakage, and caused cytotoxicity (i.e., increased levels of albumin, total protein, lactate dehydrogenase [LDH], and hemoglobin in BALF) in the airways. In summary, the spores of A. versicolor caused acute inflammation in mouse lungs. This indicates that they have potential to provoke adverse health effects in the occupants of moisture-damaged buildings.

  6. Therapeutic blockade of CD54 attenuates pulmonary barrier damage in T cell-induced acute lung injury.

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    Svedova, Julia; Ménoret, Antoine; Mittal, Payal; Ryan, Joseph M; Buturla, James A; Vella, Anthony T

    2017-07-01

    Acute respiratory distress syndrome (ARDS) is a serious, often fatal condition without available pharmacotherapy. Although the role of innate cells in ARDS has been studied extensively, emerging evidence suggests that T cells may be involved in disease etiology. Staphylococcus aureus enterotoxins are potent T-cell mitogens capable of triggering life-threatening shock. We demonstrate that 2 days after inhalation of S. aureus enterotoxin A, mice developed T cell-mediated increases in vascular permeability, as well as expression of injury markers and caspases in the lung. Pulmonary endothelial cells underwent sequential phenotypic changes marked by rapid activation coinciding with inflammatory events secondary to T-cell priming, followed by reductions in endothelial cell number juxtaposing simultaneous T-cell expansion and cytotoxic differentiation. Although initial T-cell activation influenced the extent of lung injury, CD54 (ICAM-1) blocking antibody administered well after enterotoxin exposure substantially attenuated pulmonary barrier damage. Thus CD54-targeted therapy may be a promising candidate for further exploration into its potential utility in treating ARDS patients. Copyright © 2017 the American Physiological Society.

  7. "Cromoglycate: A healing agent in acute Chlorine-induced lung damage "

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    "Pipelzadeh MH

    2002-09-01

    Full Text Available In the present study the effectiveness of sodium cromoglycate in treatment of alveolar damage induced by chlorine gas in rats was investigated. Chlorine was generated by chemical interaction between potassium permanganate and concentrated hydrochloric acid. The rats were exposed to sublethal dose of chlorine gas. Treatment with 2.5 mg of 1 ml nebulized sodium cromoglycate solution over 5 minutes was initiated 30 minutes after exposure followed by twice daily treatment for 21 days. Results of this study show that cromoglycate reduced alveolar thickness, septal rupture, hemorrhage and detachment of the epithelial lining of the bronchioles induced by chlorine gas.

  8. Contribution of neutrophils to acute lung injury.

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    Grommes, Jochen; Soehnlein, Oliver

    2011-01-01

    Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

  9. Lung Oxidative Damage by Hypoxia

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    O. F. Araneda

    2012-01-01

    Full Text Available One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described.

  10. Lung Oxidative Damage by Hypoxia

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    Araneda, O. F.; Tuesta, M.

    2012-01-01

    One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described. PMID:22966417

  11. Biomarkers in acute lung injury.

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    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.

  12. Acute exacerbations of fibrotic interstitial lung disease.

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    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.

  13. A novel Respiratory Health Score (RHS supports a role of acute lung damage and pig breed in the course of an Actinobacillus pleuropneumoniae infection

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    Gerlach Gerald F

    2009-04-01

    Full Text Available Abstract Background Bacterial lung infections are a major cause of economic losses in the pig industry; they are responsible for approximately 50% of the antibiotics used in pigs and, therefore, also present an increasing concern to consumer protection agencies. In response to this changing market we investigated the feasibility of an old approach aimed at the breeding selection of more resistant pigs. As a first step in this direction we applied a new respiratory health score system to study the susceptibility of four different pig breeding lines (German Landrace, Piétrain, Hampshire, Large White towards the respiratory tract pathogen Actinobacillus (A. pleuropneumoniae. Results A controlled experimental aerosol infection with an A. pleuropneumoniae serotype 7 isolate was performed using 106 weaning pigs of defined breeding lines from the breeds German Landrace, Piétrain, Hamphire, and Large White. Pigs were clinically assessed on days 4 and 20 post infection following a novel scoring system, the Respiratory Health Score (RHS, which combines clinical, sonographic and radiographic examination results. The ranking on day 4 was significantly correlated with the ranking based on the pathomorphological Lung Lesion Score (LLS; Spearman Rank Correlation Coefficient of 0.86 [p Conclusion These results demonstrate that the RHS obtained from live pigs shows a highly significant correlation to the lung lesion score considered as a "gold standard". The correlation of the ranking at days 4 and 20 post infection implies that the course of disease is highly dependent on the acute lung damage. The different severity of signs among the tested pig breeding lines clearly suggests a genetic difference in the susceptibility of pigs to A. pleuropneumoniae infection.

  14. Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers

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    Jensen, Jens Ulrik Stæhr; Itenov, Theis Skovsgaard; Thormar, Katrin M

    2016-01-01

    damage in intubated patients can be identified by SPD blood measurement at intensive care admission, and high SPD level is a strong independent predictor that the patient suffers from ARDS and will not recover independent respiratory function within one month. This knowledge can be used to improve...

  15. Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders

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    Riitta Kaarteenaho

    2011-01-01

    Full Text Available It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD. The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP and acute exacerbations of idiopathic pulmonary fibrosis (IPF. Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs, and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal.

  16. Irradiation damage to the lung

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    Fennessy, J.J.

    1987-07-01

    While some degree of injury to normal, non-tumor-bearing, intrathoracic structures always occurs following irradiation for cure or palliation of neoplastic disease, clinical expression of this injury is uncommon. However, under certain circumstances, clinical manifestations may be severe and life threatening. Acute radiographic manifestations of pulmonary injury usually appear either synchronous with or, more typically, seven to ten days after the onset of the clinical syndrome. The acute signs of edema and slight volume loss within the irradiated zone are nonspecific except for their temporal and spatial relationship to the irradiation of the patient. Resolution of the acute changes is followed by pulmonary cicatrization, which is almost always stable within one year after completion of therapy. Change in postirradiation scarring following stabilization of the reaction must always be assumed to be due to some other process. While the radiograph primarily reveals pulmonary injury, all tissues, including the heart and major vessels, are susceptible, and the radiologist must recognize that any change within the thorax of a patient who has undergone thoracic irradiation may be a complication of that treatment. Differentiation of irradiation injury from residual or recurrent tumor, drug reaction, or opportunistic infection may be difficult and at times impossible.

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

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    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...

  18. 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.

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

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    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.

  20. Transfusion-related acute lung injury.

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    Jawa, Randeep S; Anillo, Sergio; Kulaylat, Mahmoud N

    2008-01-01

    Transfusion-related acute lung injury (TRALI) refers to a clinical syndrome of acute lung injury that occurs in a temporal relationship with the transfusion of blood products. Because of the difficulty in making its diagnosis, TRALI is often underreported. Three not necessarily mutually exclusive hypotheses have been described to explain its etiogenesis: antibody mediated, non-antibody mediated, and two hit mechanisms. Treatment is primarily supportive and includes supplemental oxygen. Diuretics are generally not indicated, as hypovolemia should be avoided. Compared with many other forms of acute lung injury, including the acute respiratory distress syndrome, TRALI is generally transient, reverses spontaneously, and carries a better prognosis. A variety of prevention strategies have been proposed, ranging from restrictive transfusion strategies to using plasma derived only from males.

  1. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

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    Mukhopadhyay, Sanjay; Parambil, Joseph G

    2012-10-01

    Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF).

  2. Acute lung injury induces cardiovascular dysfunction

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    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...

  3. Target organ damage in acute heart failure.

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    Casado Cerrada, J; Zabaleta Camino, J P; Fontecha Ortega, M

    2016-03-01

    Acute heart failure is a prognostic factor due to its high mortality during the acute phase and the increased frequency of medium to long-term adverse events. The pathophysiological mechanisms triggered during these exacerbations can persist after reaching clinical stability, remaining even after the acute episode has ended. A certain degree of neurohormonal activation, oxidative stress, apoptosis and inflammation (among other conditions) can therefore persist, resulting in organ damage, not just of the myocardium but likely the entire cardiovascular apparatus. This new insight into the persistence of harmful mechanisms that last beyond the exacerbations could be the start of a change in perspective for developing new therapeutic strategies that seek an overall control of hemodynamic and congestive changes that occur during acute decompensated heart failure and changes that remain after achieving clinical stability. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

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

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    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.

  5. Role of Nrf2 and Autophagy in Acute Lung Injury

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    de la Vega, Montserrat Rojo; Dodson, Matthew; Gross, Christine; Manzour, Heidi; Lantz, R. Clark; Chapman, Eli; Wang, Ting; Black, Stephen M.; Garcia, Joe G.N.; Zhang, Donna D.

    2016-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. Characterized by severe inflammation and compromised lung function, ALI/ARDS result in very high mortality of affected individuals. Currently, there are no effective treatments for ALI/ARDS, and ironically, therapies intended to aid patients (specifically mechanical ventilation, MV) may aggravate the symptoms. Key events contributing to the development of ALI/ARDS are: increased oxidative and proteotoxic stresses, unresolved inflammation, and compromised alveolar-capillary barrier function. Since the airways and lung tissues are constantly exposed to gaseous oxygen and airborne toxicants, the bronchial and alveolar epithelial cells are under higher oxidative stress than other tissues. Cellular protection against oxidative stress and xenobiotics is mainly conferred by Nrf2, a transcription factor that promotes the expression of genes that regulate oxidative stress, xenobiotic metabolism and excretion, inflammation, apoptosis, autophagy, and cellular bioenergetics. Numerous studies have demonstrated the importance of Nrf2 activation in the protection against ALI/ARDS, as pharmacological activation of Nrf2 prevents the occurrence or mitigates the severity of ALI/ARDS. Another promising new therapeutic strategy in the prevention and treatment of ALI/ARDS is the activation of autophagy, a bulk protein and organelle degradation pathway. In this review, we will discuss the strategy of concerted activation of Nrf2 and autophagy as a preventive and therapeutic intervention to ameliorate ALI/ARDS. PMID:27313980

  6. Surfactant for pediatric acute lung injury.

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    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.

  7. Bleomycin and radiation-induced lung damage in mice

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    Collis, C.H.; Down, J.D.; Pearson, A.E.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1983-01-01

    Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction.

  8. [Definition and biomarkers of acute renal damage: new perspectives].

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    Seijas, M; Baccino, C; Nin, N; Lorente, J A

    2014-01-01

    The RIFLE and AKIN criteria have definitely help out to draw attention to the relationship between a deterioration of renal function that produces a small increase in serum creatinine and a worse outcome. However, the specific clinical utility of using these criteria remains to be well-defined. It is believed that the main use of these criteria is for the design of epidemiological studies and clinical trials to define inclusion criteria and objectives of an intervention. AKI adopting term, re-summoning former ARF terminology, it is appropriate to describe the clinical condition characterized by damage to kidney, in the same way as the term is used to describe acute lung damage where the lung injury situation still has not increased to a situation of organ failure (dysfunction). The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use are not sensitive or specific for detecting kidney damage, limiting treatment options and potentially compromising the outcome. New biomarkers are being studied in order to diagnose an earlier and more specific AKI, with the potential to change the definition criteria of AKI with different stages, currently based in diuresis and serum creatinine. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  9. Human models of acute lung injury

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    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.

  10. QUANTIFYING LOCAL RADIATION-INDUCED LUNG DAMAGE FROM COMPUTED TOMOGRAPHY

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    Ghobadi, Ghazaleh; Hogeweg, Laurens E.; Faber, Hette; Tukker, Wim G. J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Coppes, Robert P.; van Luijk, Peter

    2010-01-01

    Purpose: Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage re

  11. [Acute damage to the myocardium and left lung is a complication of high-frequency percutaneous thermoablation of solitary metastasis of renal cancer into the liver (a clinical observation)].

    Science.gov (United States)

    Tipisev, D A; Gorobets, E S; Agapov, A A; Zotov, A V; Kosyrev, V Iu

    2005-01-01

    The paper describes a case of severe complication of radio-frequency percutaneous thermoablation of renal metastasis into the liver, which occurred in a young woman with the intact cardiovascular system and manifested itself in the development of alveolar edema of the lung and acute dilation of the stomach. Pulmonary edema resulted from left ventricular myocardial and pulmonary parenchymal lesions and acute mitral valvular insufficiency. The authors' considerations as to the possible cause and mechanisms of development of this life-threatening complication first described in the literature are also given.

  12. Kinetic model for the pathogenesis of radiation lung damage

    Energy Technology Data Exchange (ETDEWEB)

    Collis, C.H. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1982-09-01

    The development of radiation-induced lung damage can be explained by a kinetic model, based on the assumption that this damage becomes manifest only when a critical proportion (K) of essential cells have ceased to function, and that the rate of loss of these cells following irradiation is linear and dose-dependent. The kinetic model relates the surviving fraction to the time to manifestation of radiation-induced lung damage and to constants, K and the cell cycle time, T. Predictions made from the model about the nature of the response to irradiation are, for the most part, fulfilled. The model can also be used to interpret the response to combined treatment with irradiation and cytotoxic drugs, including the much earlier manifestation of lung damage sometimes seen with such treatment.

  13. 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.

  14. The mean lung dose (MLD). Predictive criterion for lung damage

    Energy Technology Data Exchange (ETDEWEB)

    Geyer, Peter; Appold, Steffen [Dresden University of Technology (TU Dresden), Clinic and Polyclinic for Radiotherapy and Radiation Oncology, Carl Gustav Carus Medical Faculty, Dresden (Germany); Herrmann, Thomas

    2015-07-15

    The purpose of this work was to prove the validity of the mean lung dose (MLD), widely used in clinical practice to estimate the lung toxicity of a treatment plan, by reevaluating experimental data from mini pigs. A total of 43 mini pigs were irradiated in one of four dose groups (25, 29, 33, and 37 Gy). Two regimens were applied: homogeneous irradiation of the right lung or partial irradiation of both lungs - including parts with lower dose - but with similar mean lung doses. The animals were treated with five fractions with a linear accelerator applying a CT-based treatment plan. The clinical lung reaction (breathing frequency) and morphological changes in CT scans were examined frequently during the 48 weeks after irradiation. A clear dose-effect relationship was found for both regimens of the trial. However, a straightforward relationship between the MLD and the relative number of responders with respect to different grades of increased breathing frequency for both regimens was not found. A morphologically based parameter NTCP{sub lung} was found to be more suitable for this purpose. The dependence of this parameter on the MLD is markedly different for the two regimens. In clinical practice, the MLD can be used to predict lung toxicity of a treatment plan, except for dose values that could lead to severe side effects. In the latter mentioned case, limitations to the predictive value of the MLD are possible. Such severe developments of a radiation-induced pneumopathy are better predicted by the NTCP{sub lung} formalism. The predictive advantage of this parameter compared to the MLD seems to remain in the evaluation and comparison of widely differing dose distributions, like in the investigated trial. (orig.) [German] Es soll unter Reevaluation von Tierversuchsdaten am Minischwein geprueft werden, ob die in der klinischen Praxis zur Beurteilung der Lungentoxizitaet eines Bestrahlungsregims regelhaft verwendete mittlere Lungendosis (MLD) eine zuverlaessige

  15. Acute lung injury, overhydration or both?

    Science.gov (United States)

    Groeneveld, A B Johan; Polderman, Kees H

    2005-04-01

    Acute lung injury or acute respiratory distress syndrome (ALI/ARDS) in the course of sepsis is thought to result from increased pulmonary capillary permeability and resultant edema. However, when the edema is assessed at the bedside by measuring the extravascular thermal volume by transpulmonary dilution, some ALI/ARDS patients with sepsis may have normal extravascular lung water (EVLW). Conversely, a raised EVLW may be present even when criteria for ALI/ARDS are not met, according to GS Martin and colleagues in this issue of Critical Care. This commentary puts the findings into a broader perspective and focuses on the difficulty, at the bedside, in recognizing and separating various types of pulmonary edema. Some of these forms of edema, classically differentiated on the basis of increased permeability and cardiogenic/hydrostatic factors, may overlap, whereas the criteria for ALI/ARDS may be loose, poorly reproducible, relatively insensitive and nonspecific, and highly therapy-dependent. Overhydration is particularly difficult to recognize. Additional diagnostics may be required to improve the delineation of pulmonary edema so as to redirect or redefine treatment and improve patient morbidity and, perhaps, mortality. Monitoring EVLW by single transpulmonary thermal dilution, for instance, might have a future role in this process.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis.

    Science.gov (United States)

    Rahman, Milladur; Gustafsson, David; Wang, Yongzhi; Thorlacius, Henrik; Braun, Oscar Ö

    2014-01-01

    Abstract Platelets play an important role in abdominal sepsis and P2Y12 receptor antagonists have been reported to exert anti-inflammatory effects. Herein, we assessed the impact of platelet inhibition with the P2Y12 receptor antagonist ticagrelor on pulmonary neutrophil recruitment and tissue damage in a model of abdominal sepsis. Wild-type C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Animals were treated with ticagrelor (100 mg/kg) or vehicle prior to CLP induction. Edema formation and bronchoalveolar neutrophils as well as lung damage were quantified. Flow cytometry was used to determine expression of platelet-neutrophil aggregates, neutrophil activation and CD40L expression on platelets. CLP-induced pulmonary infiltration of neutrophils at 24 hours was reduced by 50% in ticagrelor-treated animals. Moreover, ticagrelor abolished CLP-provoked lung edema and decreased lung damage score by 41%. Notably, ticagrelor completely inhibited formation of platelet-neutrophil aggregates and markedly reduced thrombocytopenia in CLP animals. In addition, ticagrelor reduced platelet shedding of CD40L in septic mice. Our data indicate that ticagrelor can reduce CLP-induced pulmonary neutrophil recruitment and lung damage suggesting a potential role for platelet antagonists, such as ticagrelor, in the management of patients with abdominal sepsis.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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....

  6. THE 5-LIPOXYGENASE PATHWAY IS REQUIRED FOR ACUTE LUNG INJURY FOLLOWING HEMORRHAGIC SHOCK

    Science.gov (United States)

    Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijón, Miguel A.; Murphy, Robert C.

    2012-01-01

    The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury. PMID:22392149

  7. DIETARY FLAXSEED PREVENTS RADIATION-INDUCED OXIDATIVE LUNG DAMAGE, INFLAMMATION AND FIBROSIS IN A MOUSE MODEL OF THORACIC RADIATION INJURY

    Science.gov (United States)

    Lee, James C.; Krochak, Ryan; Blouin, Aaron; Kanterakis, Stathis; Chatterjee, Shampa; Arguiri, Evguenia; Vachani, Anil; Solomides, Charalambos C.; Cengel, Keith A.; Christofidou-Solomidou, Melpo

    2009-01-01

    Flaxseed (FS) has high contents of omega-3 fatty acids and lignans with antioxidant properties. Its use in preventing thoracic X-ray radiation therapy (XRT)-induced pneumonopathy has never been evaluated. We evaluated FS supplementation given to mice given before and post-XRT. FS-derived lignans, known for their direct antioxidant properties, were evaluated in abrogating ROS generation in cultured endothelial cells following gamma radiation exposure. Mice were fed 10% FS or isocaloric control diet for three weeks and given 13.5 Gy thoracic XRT. Lungs were evaluated at 24 hours for markers of radiation-induced injury, three weeks for acute lung damage (lipid peroxidation, lung edema and inflammation), and at four months for late lung damage (inflammation and fibrosis). FS-Lignans blunted ROS generation in vitro, resulting from radiation in a dose-dependent manner. FS-fed mice had reduced expression of lung injury biomarkers (Bax, p21, and TGF-beta1) at 24 hours following XRT and reduced oxidative lung damage as measured by malondialdehyde (MDA) levels at 3 weeks following XRT. In addition, FS-fed mice had decreased lung fibrosis as determined by hydroxyproline content and decreased inflammatory cell influx into lungs at 4 months post XRT. Importantly, when Lewis Lung carcinoma cells were injected systemically in mice, FS dietary supplementation did not appear to protect lung tumors from responding to thoracic XRT. Dietary FS is protective against pulmonary fibrosis, inflammation and oxidative lung damage in a murine model. Moreover, in this model, tumor radioprotection was not observed. FS lignans exhibited potent radiation-induced ROS scavenging action. Taken together, these data suggest that dietary flaxseed may be clinically useful as an agent to increase the therapeutic index of thoracic XRT by increasing the radiation tolerance of lung tissues. PMID:18981722

  8. 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

  9. 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

  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. 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

  12. 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.

  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. Diagnosis of Lung Cancer by Fractal Analysis of Damaged DNA

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2015-01-01

    Full Text Available Cancer starts when cells in a part of the body start to grow out of control. In fact cells become cancer cells because of DNA damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to study the cancer genes, DNA walk plots of genomes of patients with lung cancer were generated using a program written in MATLAB language. The data so obtained was checked for fractal property by computing the fractal dimension using a program written in MATLAB. Also, the correlation of damaged DNA was studied using the Hurst exponent measure. We have found that the damaged DNA sequences are exhibiting higher degree of fractality and less correlation compared with normal DNA sequences. So we confirmed this method can be used for early detection of lung cancer. The method introduced in this research not only is useful for diagnosis of lung cancer but also can be applied for detection and growth analysis of different types of cancers.

  16. 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.

  17. Lung tissue remodeling in the acute respiratory distress syndrome

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    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.

  18. 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

  19. 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

  20. 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.

  1. Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

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    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.

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

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    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.

  3. Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling

    Science.gov (United States)

    Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

    2015-01-01

    Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells. PMID:26396176

  4. RAGE/NF-κB signaling mediates lipopolysaccharide induced acute lung injury in neonate rat model.

    Science.gov (United States)

    Li, Yuhong; Wu, Rong; Tian, Yian; Yu, Min; Tang, Yun; Cheng, Huaipin; Tian, Zhaofang

    2015-01-01

    Lipopolysaccharide (LPS) is known to induce acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Accumulating data suggest the crucial role of RAGE in the pathogenesis of ALI/ARDS. However, the mechanism by which RAGE mediates inflammatory lung injury in the neonates remains elusive. In this study we established LPS-induced ALI model in neonate rats, and investigated the role of RAGE/NF-κB signaling in mediating ALI. We found that RAGE antibody or bortezomib reduced LPS-induced histopathological abnormalities in the lung and lung damage score. RAGE antibody or bortezomib also reduced TNF-α level in both serum and BALF of the rats. Furthermore, RAGE antibody or bortezomib significantly reduced LPS-induced upregulation of RAGE and NF-κB expression in the lung. In conclusion, we established ALI model in neonate rats to demonstrate that LPS induced inflammatory lung injury via RAGE/NF-κB signaling. Interference with RAGE/NF-κB signaling is a potential approach to prevent and treat sepsis-related ALI/ARDS.

  5. 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.

  6. 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.

  7. Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    Science.gov (United States)

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-08-01

    Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese

  8. Endotoxin-induced lung alveolar cell injury causes brain cell damage

    Science.gov (United States)

    Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia RM; Pelosi, Paolo

    2015-01-01

    Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. PMID:25135986

  9. 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.

  10. 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.

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

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    REYHANEH SEPEHR

    2013-07-01

    Full Text Available 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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....

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

    Directory of Open Access Journals (Sweden)

    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

  17. Cardiotrophin-1 attenuates endotoxin-induced acute lung injury.

    Science.gov (United States)

    Pulido, E J; Shames, B D; Pennica, D; O'leary, R M; Bensard, D D; Cain, B S; McIntyre, R C

    1999-06-15

    Cardiotrophin-1 (CT-1) is a recently discovered member of the gp130 cytokine family, which includes IL-6, IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Recent evidence suggests that, like other members of this family, CT-1 may possess anti-inflammatory properties. We hypothesized that in vivo CT-1 administration would attenuate endotoxin (ETX)-induced acute lung injury. We studied the effects of CT-1 (100 microgram/kg ip, 10 min prior to ETX) in a rat model of ETX-induced acute lung injury (Salmonella typhimurium lipopolysaccharide, 20 mg/kg ip). Six hours after ETX, lungs were harvested for determination of neutrophil accumulation (myeloperoxidase, MPO, assay) and lung edema (wet-to-dry weight ratio). Mechanisms of pulmonary vasorelaxation were examined in isolated pulmonary artery rings at 6 h by interrogating endothelium-dependent (response to acetylcholine) and endothelium-independent (response to sodium nitroprusside) relaxation following alpha-adrenergic (phenylephrine)-stimulated preconstriction. CT-1 abrogated the endotoxin-induced lung neutrophil accumulation: 2.3 +/- 0.2 units MPO/g wet lung (gwl) vs 6. 3 +/- 0.3 units MPO/gwl in the ETX group (P 0.05 vs control). Similarly, CT-1 prevented ETX-induced lung edema: wet-to-dry-weight ratio, 4.473 +/- 0.039 vs 4.747 +/- 0.039 in the ETX group (P 0.05 vs control). Endotoxin caused significant impairment of both endothelium-dependent and -independent pulmonary vasorelaxation, and CT-1 attenuated this injury. Thus, cardiotrophin-1 possesses significant anti-inflammatory properties in a model of endotoxin-induced acute lung injury. Copyright 1999 Academic Press.

  18. 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

  19. 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

  20. 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,

  1. 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

  2. Sox9 Activation is Essential for the Recovery of Lung Function after Acute Lung Injury

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    Lei Li

    2015-09-01

    Full Text Available Background/Aims: Acute lung injury (ALI often predisposes acute respiratory distress syndrome (ARDS in humans, and is featured with neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Although the pathogenesis of ALI is relatively well studied, the knowledge on the molecular regulation of the post-ALI lung recovery are poorly understood. Methods: Here, we used a widely applied bleomycin-induced ALI model to study the molecular mechanisms that underlie the post-ALI lung recovery in mice. We analyzed Sox9 expression in mouse lung by RT-qPCR, Western blot and immunohistochemistry. We analyzed miR-101 levels in mouse lung by RT-qPCR. We inhibited Sox9 in mouse lung by expressing either shRNA for Sox9 or miR-101, and analyzed the effects of Sox9 suppression on lung recovery. Results: We detected a significant increase in Sox9 protein but not mRNA, and a signifcant decrease in miR-101 levels in the mouse lung after ALI. MiR-101 was found to target 3'-UTR of Sox9 mRNA to inhibit its expression. Sox9 inhibition by either shRNA for Sox9 or by miR-101 further impaired the functional recovery of the lung after ALI. Conclusion: Our data suggest that Sox9 activation is essential for the recovery of lung function after ALI, which highlights a previously unappreciated mechanism that controls the post-ALI lung recovery.

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

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    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.

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

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    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

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

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    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

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

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    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.

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

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    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.

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

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    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

  9. RAGE inhibition reduces acute lung injury in mice.

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    Blondonnet, Raiko; Audard, Jules; Belville, Corinne; Clairefond, Gael; Lutz, Jean; Bouvier, Damien; Roszyk, Laurence; Gross, Christelle; Lavergne, Marilyne; Fournet, Marianne; Blanchon, Loic; Vachias, Caroline; Damon-Soubeyrand, Christelle; Sapin, Vincent; Constantin, Jean-Michel; Jabaudon, Matthieu

    2017-08-03

    The receptor for advanced glycation end-products (RAGE) is involved in inflammatory response during acute respiratory distress syndrome (ARDS). Growing body of evidence support strategies of RAGE inhibition in experimental lung injury, but its modalities and effects remain underinvestigated. Anesthetised C57BL/6JRj mice were divided in four groups; three of them underwent orotracheal instillation of acid and were treated with anti-RAGE monoclonal antibody (mAb) or recombinant soluble RAGE (sRAGE), acting as a decoy receptor. The fourth group served as a control. Lung injury was assessed by the analysis of blood gases, alveolar permeability, histology, AFC, and cytokines. Lung expression and distribution epithelial channels ENaC, Na,K-ATPase, and aquaporin (AQP)-5 were assessed. Treatment with either anti-RAGE mAb or sRAGE improved lung injury, arterial oxygenation and decreased alveolar inflammation in acid-injured animals. Anti-RAGE therapies were associated with restored AFC and increased lung expression of AQP-5 in alveolar cell. Blocking RAGE had potential therapeutic effects in a translational mouse model of ARDS, possibly through a decrease in alveolar type 1 epithelial cell injury as shown by restored AFC and lung AQP-5 expression. Further mechanistic studies are warranted to describe intracellular pathways that may control such effects of RAGE on lung epithelial injury and repair.

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

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    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.

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

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    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.

  12. RESPIRATORY VIRAL-INFECTIONS AGGRAVATE AIRWAY DAMAGE CAUSED BY CHRONIC REJECTION IN RAT LUNG ALLOGRAFTS

    NARCIS (Netherlands)

    WINTER, JB; GOUW, ASH; GROEN, M; WILDEVUUR, C; PROP, J

    1994-01-01

    Airway damage resulting in bronchiolitis obliterans occurs frequently in patients after heart-lung and lung transplantation. Generally, chronic rejection is assumed to be the most important cause of bronchiolitis obliterans. However, viral infections might also be potential causes of airway damage a

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

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    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.

  14. [Protective effect of synthetic salidroside on acute lung injury in rats].

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    Huang, Qian; Cai, Yan-Chun; Wei, Xiao-Li; Wu, Jin-Long; Mei, Ru-Huan; Hu, Xiao-Lan

    2017-06-25

    To study the protective effect and mechanism of synthetic salidroside on acute lung injury (ALI) induced by lipopolysaccharide (LPS), male Sprague-Dawley (SD) rats were randomly divided into saline control group, 3 mg/kg LPS model group, different doses of salidroside groups (5, 20 and 80 mg/kg), and 5 mg/kg dexamethasone group. Intratracheal LPS instillation was used to establish the ALI model 0.5 h after intraperitoneal injection of salidroside or dexamethasone, and the rats were sacrificed 6 h later. Lung wet/dry weight ratio (W/D) was calculated. Lung tissue pathology and lung injury score (LIS) were observed and evaluated through hematoxylin and eosin (HE) staining. The centrifugal sediment of bronchoalveolar lavage fluid (BALF) was used to count the polymorphonuclear leukocyte (PMN) number by Wright's staining, and the centrifugal supernatant of BALF was used to determine the contents of protein and inflammatory factors (TNF-α, IL-1β and IL-6). The contents of myeloperoxidase (MPO) and malondialdehyde (MDA) in lung tissue were determined. Western blot was used to detect the expression levels of phosphorylated and total nuclear factor kappa B (NF-κB)/p65 protein in lung tissue. The results showed that, compared with LPS group, the intervention of synthetic salidroside alleviated the pathological damage in lung tissue, decreased the LIS and lung W/D ratio (P salidroside has a protective effect on ALI induced by LPS, and its mechanism is related to inhibiting the phosphorylation of NF-κB and reducing the aggregation of PMN in the lung.

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

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    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.

  16. Dose-dependence of the time of appearance of lung damage in mice given thoracic irradiation

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    Collis, C.H.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1982-09-01

    Male CBA mice were given X-radiation to the thorax in the range 7 to 23 Gy and their response was quantified by measuring ventilation rate and carbon monoxide uptake at intervals up to 2 years thereafter; their survival was also documented. The two functional end-points were similarly sensitive indicators of lung damage. Radiation damage was not observed below 10 Gy. As radiation dose was raised above this level there was a rapid shortening of the time to the appearance of damage and subsequent death. At a dose of 15 Gy the median survival time was 14 weeks but raising the dose above this level only slightly reduced the survival time. The way in which the time of survival after lung damage depends on dose is an important characteristic of the development of radiation-induced lung damage which should be considered when examining factors that may influence the development of radiation-induced lung damage.

  17. 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.

  18. 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.

  19. [Role of autophagy in ameliorating sepsis-induced acute lung injury by allicinin in mice].

    Science.gov (United States)

    Peng, Yue; Jiang, Yu; Ou, Hao; Xing, Wei; Yang, Mingshi; Gao, Min

    2017-08-28

    To investigate roles of autophagy in ameliorating sepsis-induced acute lung injury by allicinin in mice.
 Methods: A total of 152 male Balb/c mice (8-week old) were randomly divided into a sham group, a septic model group, an allicin treatment group, and an autophagy inhibition group. Septic mouse model was established by cecal ligation and puncture (CLP). Mice in the allicin treatment group were given allicin (30 mg/kg, intra-peritoneal injection) at 6 and 12 h, while those in the autophagy inhibition group were given autophagy inhibitor 3-MA (15 mg/kg, intra-peritoneal injection) at half an hour after allicin administration. Mice in the model and sham group were administered with the same amount of saline. Twenty mice in each group were randomly chosen to observe the 7 d survival rate. The other 12 mice were killed at 24 h, and the bronchoalveolar lavage fluid (BALF) (n=6) and lung tissues (n=6) were collected. ELISA was used to detect the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF. Hematoxylin-eosin staining was preformed to show the morphological changes in the lung tissues. Malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) in the lung tissues were examined. The expression of LC3B and Beclin-1 was determined by immunohistochemical analysis.
 Results: Compared with the sham group, the 7 d survival rate and lung SOD activity were decreased in the CLP group (P<0.05); the lung morphological damage score, the levels of TNF-α and IL-6 in the BALF, MDA content in the lung, and expression of LC3B and Beclin-1 were increased greatly in the CLP group (P<0.05). Compared with the CLP group, the 7 d survival rate, lung SOD activity and the expressions of LC3B and Beclin-1 were increased significantly in the allicin treatment group (P<0.05); the lung morphological damage scores, the levels of TNF-α and IL-6 in the BALF and MDA content in the lung were decreased obviously in the allicin treatment group (P<0

  20. 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.

  1. Unilateral Hydronephrosis and Renal Damage after Acute Leukemia

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    Egle Simanauskiene

    2012-01-01

    Full Text Available A 14-year-old boy presented with asymptomatic right hydronephrosis detected on routine yearly ultrasound examination. Previously, he had at least two normal renal ultrasonograms, 4 years after remission of acute myeloblastic leukemia, treated by AML-BFM-93 protocol. A function of the right kidney and no damage on the left was confirmed by a DMSA scan. Right retroperitoneoscopic nephrectomy revealed 3 renal arteries with the lower pole artery lying on the pelviureteric junction. Histologically chronic tubulointerstitial nephritis was detected. In the pathogenesis of this severe unilateral renal damage, we suspect the exacerbation of deleterious effects of cytostatic therapy on kidneys with intermittent hydronephrosis.

  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. Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS production.

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    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.

  4. Peptide nanomedicines for treatment of acute lung injury.

    Science.gov (United States)

    Sadikot, Ruxana T

    2012-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients. Despite the increased understanding of the molecular pathogenesis of ARDS, the mortality remains unacceptably high, ranging from 34% to 64%. Hence, ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Several promising targets that have been identified as potential therapies for ARDS have been limited because of difficulty with delivery. In particular, delivery of peptides and proteins to the lung is an ongoing challenge. Nanobiotechnology and nanoscience are the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmakodynamics of agents allowing an increase in the biodistribution of therapeutic agents to target organs, resulting in improved efficacy with reduction in drug toxicity. These systems are exploited for therapeutic purpose to carry the drug in the body in a controlled manner from the site of administration to the therapeutic target. Hence, it is an attractive strategy to test potential targets for ALI/ARDS using nanotechnology. To this end, we have identified several potential targets and proposed the delivery of these agents using nanomicelles to improve the drug delivery. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Oxidative Damage to Lung Tissue and Peripheral Blood in Endotracheal PM2.5-treated Rats

    Institute of Scientific and Technical Information of China (English)

    ZHI-QING LIN; ZHU-GE XI; DAN-FENG YANG; FU-HUAN CHAO; HUA-SHAN ZHANG; WEI ZHANG; HUANG-LIANG LIU; ZAI-MING YANG; RU-BAO SUN

    2009-01-01

    Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats.Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter.Treated samples were endotracheally instilled into rats.Activity of reduced glutathione peroxidase (GSH-Px) and concentration of malondialdehyde (MDA) were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method.DNA migration length (μm) and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days.In peripheral blood,the concentration of MDA decreased,but the activity of GSH-Px increased 7 and 14 days after experiments.The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood.The DNA migration length (μm) and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5.The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood.The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5.The DNA migration length (μm) and rate of tail are simple and valuable biomarkers of PM2.5-induced DNA damage in lung tissues and peripheral blood.The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

  6. 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

  7. 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

  8. Interleukin-19 mediates tissue damage in murine ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Yu-Hsiang Hsu

    Full Text Available Inflammation and renal tubular injury are major features of acute kidney injury (AKI. Many cytokines and chemokines are released from injured tubular cells and acts as proinflammatory mediators. However, the role of IL-19 in the pathogenesis of AKI is not defined yet. In bilateral renal ischemia/reperfusion injury (IRI-induced and HgCl2-induced AKI animal models, real-time quantitative (RTQ-PCR showed that the kidneys, livers, and lungs of AKI mice expressed significantly higher IL-19 and its receptors than did sham control mice. Immunohistochemical staining showed that IL-19 and its receptors were strongly stained in the kidney, liver, and lung tissue of AKI mice. In vitro, IL-19 upregulated MCP-1, TGF-β1, and IL-19, and induced mitochondria-dependent apoptosis in murine renal tubular epithelial M-1 cells. IL-19 upregulated TNF-α and IL-10 in cultured HepG2 cells, and it increased IL-1β and TNF-α expression in cultured A549 cells. In vivo, after renal IRI or a nephrotoxic dose of HgCl2 treatment, IL-20R1-deficient mice (the deficiency blocks IL-19 signaling showed lower levels of blood urea nitrogen (BUN in serum and less tubular damage than did wild-type mice. Therefore, we conclude that IL-19 mediates kidney, liver, and lung tissue damage in murine AKI and that blocking IL-19 signaling may provide a potent therapeutic strategy for treating AKI.

  9. Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs.

    Science.gov (United States)

    Lin, Chia-Chih; Hsieh, Nan-Kuang; Liou, Huey Ling; Chen, Hsing I

    2012-03-01

    Phorbol myristate acetate (PMA) is a strong neutrophil activator and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC) on the PMA-induced ALI and associated changes. The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 μg/g), PMA 4 μg/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc) were determined in isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS). The neutrophil-derived mediators in lung perfusate were determined. PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental role in the PMA-induced lung injury. ATP is beneficial

  10. Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs

    Directory of Open Access Journals (Sweden)

    Lin Chia-Chih

    2012-03-01

    Full Text Available Abstract Background Phorbol myristate acetate (PMA is a strong neutrophil activator and has been used to induce acute lung injury (ALI. Niacinamide (NAC is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC on the PMA-induced ALI and associated changes. Methods The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 μg/g, PMA 4 μg/g (lung weight, cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight. There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc were determined in isolated lungs. ATP (adenotriphosphate and PARP [poly(adenosine diphophate-ribose polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS. The neutrophil-derived mediators in lung perfusate were determined. Results PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. Conclusions Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental

  11. Altered mucosal immune response after acute lung injury in a murine model of Ataxia Telangiectasia.

    Science.gov (United States)

    Eickmeier, Olaf; Kim, Su Youn; Herrmann, Eva; Döring, Constanze; Duecker, Ruth; Voss, Sandra; Wehner, Sibylle; Hölscher, Christoph; Pietzner, Julia; Zielen, Stefan; Schubert, Ralf

    2014-05-29

    Ataxia telangiectasia (A-T) is a rare but devastating and progressive disorder characterized by cerebellar dysfunction, lymphoreticular malignancies and recurrent sinopulmonary infections. In A-T, disease of the respiratory system causes significant morbidity and is a frequent cause of death. We used a self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)- deficient mice (Atm(-/-)). ATM deficiency increased peak lung inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL-6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm(-/-) mice. ATM deficiency increased airway resistance and tissue compliance before ALI was performed. Together, these findings indicate that ATM plays a key role in inflammatory response after airway mucosal injury.

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

    Science.gov (United States)

    Kus, Tulay; Aktas, Gokmen; Sevinc, Alper; Kalender, Mehmet Emin; Camci, Celaletdin

    2015-01-01

    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. PMID:26150726

  13. Smoking-promoted oxidative DNA damage response is highly correlated to lung carcinogenesis.

    Science.gov (United States)

    Cao, Chao; Lai, Tianwen; Li, Miao; Zhou, Hongbin; Lv, Dan; Deng, Zaichun; Ying, Songmin; Chen, Zhihua; Li, Wen; Shen, Huahao

    2016-04-05

    Oxidative stress induced by tobacco smoking is one of the main causes of DNA damage and is known to be involved in various cancers. Smoking is the leading cause of lung cancer, while the role of cigarette smoke-induced oxidative DNA damage response during lung carcinogenesis is largely unknown. In this study, we investigated oxidative DNA damage response levels in smoking and nonsmoking patients with lung cancer, and evaluated the potential diagnostic value of 8-OHdG for lung cancer. We observed a higher level of 8-OHdG expression and secretion in airways of lung cancer patients than that of noncancer controls. 8-OHdG expression was associated with the TNM stages. Additionally, cigarette smoke-induced oxidative DNA damage response was observed in bronchial epithelial cells in vitro and in vivo. A statistical significance correlation was found between the levels of 8-OHdG and smoking index. With a cut-off value of 2.86 ng/ml, 8-OHdG showed a sensitivity and specificity of 70.0% and 73.7%, respectively, to identify a patient with lung cancer. These findings not only underscore the importance of smoking in oxidative DNA damage response of lung cancer patients, but also suggest 8-OHdG as a potential diagnostic biomarker for lung cancer.

  14. 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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. 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.

  16. 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.)

  17. DNA damage in lung after oral exposure to diesel exhaust particles in Big Blue (R) rats

    DEFF Research Database (Denmark)

    Müller, Anne Kirstine; Farombi, E.O.; Møller, P.

    2004-01-01

    . Lung tissue is a target organ for DEP induced cancer following inhalation. Recent studies have provided evidence that the lung is also a target organ for DNA damage and cancer after oral exposure to other complex mixtures of PAHs. The genotoxic effect of oral administration of DEP was investigated...

  18. A new CT-based method to quantify radiation-induced lung damage in patients.

    Science.gov (United States)

    Ghobadi, Ghazaleh; Wiegman, Erwin M; Langendijk, Johannes A; Widder, Joachim; Coppes, Robert P; van Luijk, Peter

    2015-10-01

    A new method to assess radiation-induced lung toxicity (RILT) using CT-scans was developed. It is more sensitive in detecting damage and corresponds better to physician-rated radiation pneumonitis than routinely-used methods. Use of this method may improve lung toxicity assessment and thereby facilitate development of more accurate predictive models for RILT.

  19. Black tea prevents cigarette smoke-induced apoptosis and lung damage

    Directory of Open Access Journals (Sweden)

    Chattopadhyay Dhrubajyoti

    2007-02-01

    Full Text Available Abstract Background Cigarette smoking is a major cause of lung damage. One prominent deleterious effect of cigarette smoke is oxidative stress. Oxidative stress may lead to apoptosis and lung injury. Since black tea has antioxidant property, we examined the preventive effect of black tea on cigarette smoke-induced oxidative damage, apoptosis and lung injury in a guinea pig model. Methods Guinea pigs were subjected to cigarette smoke exposure from five cigarettes (two puffs/cigarette per guinea pig/day for seven days and given water or black tea to drink. Sham control guinea pigs were exposed to air instead of cigarette smoke. Lung damage, as evidenced by inflammation and increased air space, was assessed by histology and morphometric analysis. Protein oxidation was measured through oxyblot analysis of dinitrophenylhydrazone derivatives of the protein carbonyls of the oxidized proteins. Apoptosis was evidenced by the fragmentation of DNA using TUNEL assay, activation of caspase 3, phosphorylation of p53 as well as over-expression of Bax by immunoblot analyses. Results Cigarette smoke exposure to a guinea pig model caused lung damage. It appeared that oxidative stress was the initial event, which was followed by inflammation, apoptosis and lung injury. All these pathophysiological events were prevented when the cigarette smoke-exposed guinea pigs were given black tea infusion as the drink instead of water. Conclusion Cigarette smoke exposure to a guinea pig model causes oxidative damage, inflammation, apoptosis and lung injury that are prevented by supplementation of black tea.

  20. 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.

  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. Acute lung injury after instillation of human breast milk or infant formula into rabbits' lungs.

    Science.gov (United States)

    O'Hare, B; Lerman, J; Endo, J; Cutz, E

    1996-06-01

    Recent interest in shortening the fasting interval after ingestion of milk products demonstrated large volumes of breast milk in the stomach 2 h after breastfeeding. Although aspiration is a rare event, if it were to occur with human breast milk, it is important to understand the extent of the lung injury that might occur. Therefore, the response to instillation of acidified breast milk and infant formula in the lungs of adult rabbits was studied. In 18 anesthetized adult rabbits, 1 of 3 fluids (in a volume of 0.8 ml.kg-1 and pH level of 1.8, acidified with hydrochloric acid); saline, breast milk, or infant formula (SMA, Wyeth, Windsor, Ontario), was instilled into the lungs via a tracheotomy. The lungs were ventilated for 4 h after instillation. Alveolar-to-arterial oxygen gradient and dynamic compliance were measured before and at hourly intervals after instillation. After 4 h, the rabbits were killed and the lungs were excised. Neutrophil infiltration was quantitated by a pathologist blinded to the instilled fluid. A histologic control group of four rabbits was ventilated under study conditions without any intratracheal fluid instillation. Alveolar-to-arterial oxygen gradient increased and dynamic compliance decreased significantly during the 4 h after instillation of both breast milk and infant formula compared with baseline measurements and with saline controls (P formula rabbits were significantly greater than those in the control group. Instillation of acidified breast milk or infant formula (in a volume of 0.8 ml.kg-1 and pH level of 1.8) into rabbits' lungs induces acute lung injury of similar intensity that lasts at least 4 h.

  3. [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.

  4. 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) ha...

  5. 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.

  6. 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

  7. 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.

  8. VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

    Science.gov (United States)

    Carapau, Daniel; Pena, Ana C.; Ataíde, Ricardo; Monteiro, Carla A. A.; Félix, Nuno; Costa-Silva, Artur; Marinho, Claudio R. F.; Dias, Sérgio; Mota, Maria M.

    2010-01-01

    The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies. PMID:20502682

  9. Hepatic damage during acute pancreatitis in the rat

    Directory of Open Access Journals (Sweden)

    A.M.M. Coelho

    1997-08-01

    Full Text Available We studied the alterations in the metabolism of liver mitochondria in rats with acute pancreatitis. Male Wistar rats were allocated to a control group (group I and to five other groups corresponding to 2, 4, 12, 24 and 48 h after the induction of acute pancreatitis by the injection of 5% sodium taurocholate into the pancreatic duct. Sham-operated animals were submitted to the same surgical steps except for the induction of acute pancreatitis. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption without ADP (basal respiration, state 4 and in the presence of ADP (activated respiration, state 3. Serum amylase, transaminases (ALT and AST and protein were also determined. Ascitic fluid, contents of amylase, trypsin and total protein were also determined and arterial blood pressure was measured in all groups. In ascitic fluid, trypsin and amylase increased reaching a maximum at 2 and 4 h, respectively. Serum amylase increased at 2 h reaching a maximum at 4 h. Serum transaminase levels increased at 12 and 24 h. After 2 h (and also 4 h there was an increase in state 4 respiration (45.65 ± 1.79 vs 28.96 ± 1.50 and a decrease in respiration control rate (3.53 ± 0.09 vs 4.45 ± 0.08 and in the ADP/O ratio (1.77 ± 0.02 vs 1.91 ± 0.01 compared to controls (P<0.05. These results indicate a disruption of mitochondrial function, which recovered after 12 h. In the 48-h groups there was mitochondrial damage similar to that occurring in ischemic lesion. Beat-to-beat analysis (30 min showed that arterial blood pressure remained normal up to 24 h (111 ± 3 mmHg while a significant decrease occurred in the 48-h group (91 ± 4 mmHg. These data suggest biphasic damage in mitochondrial function in acute pancreatitis: an initial uncoupled phase, possibly secondary to enzyme activity, followed by a temporary recovery and then a late and final dysfunction, associated with arterial hypotension, possibly related

  10. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China); Qiao, Juan, E-mail: qjuan@tsinghua.edu.cn [Department of Chemistry, Tsinghua University, Beijing 100084 (China); Lu, Yun, E-mail: luyun@tsinghua.edu.cn [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China)

    2016-02-13

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  11. 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.

  12. Vascular pharmacology of acute lung injury and acute respiratory distress syndrome.

    Science.gov (United States)

    Groeneveld, A B Johan

    2002-11-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) following sepsis, major trauma and surgery are leading causes of respiratory insufficiency, warranting artificial ventilation in the intensive care unit. It is caused by an inflammatory reaction in the lung upon exogenous or endogenous etiologies eliciting proinflammatory factors, and results in increased alveolocapillary permeability and protein-rich alveolar edema. The interstitial and alveolar inflammation and edema alter ventilation perfusion matching, gas exchange and mechanical properties of the lung. The current therapy of the condition is supportive, paying careful attention to fluid balance, relieving the increased work of breathing and improving gas exchange by mechanical ventilation, but in vitro, animal and some clinical research is done to evaluate the value of anti-inflammatory therapies on morbidity and outcome, including inflammatory cell-stabilizing corticosteroids, xanthine derivates, prostanoids and inhibitors, O(2) radical scavenging factors such as N-acetylcysteine, surfactant replacement, vasodilators including inhaled nitric oxide, vasoconstrictors such as almitrine, and others. None of these compounds has been proven to benefit survival in patients, however, even though carrying a physiologic benefit, except perhaps for steroids that may improve outcome in the later stage of ARDS. This partly relates to the difficulty to assess the lung injury at the bedside, to the multifactorial pathogenesis and the severity of comorbidity, adversely affecting survival.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. Endothelial glycocalyx damage is associated with leptospirosis acute kidney injury.

    Science.gov (United States)

    Libório, Alexandre Braga; Braz, Marcelo Boecker Munoz; Seguro, Antonio Carlos; Meneses, Gdayllon C; Neves, Fernanda Macedo de Oliveira; Pedrosa, Danielle Carvalho; Cavalcanti, Luciano Pamplona de Góes; Martins, Alice Maria Costa; Daher, Elizabeth de Francesco

    2015-03-01

    Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage.

  16. [Expression of various matrix metalloproteinases in mice with hyperoxia-induced acute lung injury].

    Science.gov (United States)

    Zhang, Xiang-feng; Ding, Shao-fang; Gao, Yuan-ming; Liang, Ying; Foda, Hussein D

    2006-08-01

    To investigate the role of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducer (EMMPRIN) in the pathogenesis of acute lung injury induced by hyperoxia. Fifty four mice were exposed in sealed cages to >98% oxygen (for 24-72 hours), and another 18 mice to room air. The severity of lung injury was assessed, and the expression of mRNA and protein of MMP-2, MMP-9 and EMMPRIN in lung tissue, after exposure for 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Hyperoxia caused acute lung injury; this was accompanied by increased expression of an upregulation of MMP-2, MMP-9 and EMMPRIN mRNA and protein in lung tissues. Hyperoxia causes acute lung injury in mice; increases in MMP-2, MMP-9 and EMMPRIN may play an important role in the development of hyperoxia induced lung injury in mice.

  17. 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.

  18. Surfactant protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage

    DEFF Research Database (Denmark)

    Johansson, Sofie L.; Tan, Qihua; Holst, René;

    2014-01-01

    Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The associat......Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage...... or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 second and forced vital capacity in the presence of current tobacco smoking but not in non...... with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive...

  19. Treadmill Exercise Preconditioning Attenuates Lung Damage Caused by Systemic Endotoxemia in Type 1 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Ching-Hsia Hung

    2013-01-01

    Full Text Available Endotoxemia induces a series of inflammatory responses that may result in lung injury. However, heat shock protein72 (HSP72 has the potential to protect the lungs from damage. The objective of this study was to determine whether prior exercise conditioning could increase the expression of HSP72 in the lungs and attenuate lung damage in diabetic rats receiving lipopolysaccharide (LPS. Streptozotocin was used to induce diabetes in adult male Wistar rats. Rats were randomly assigned to sedentary or exercise groups. Rats in the exercise condition ran on a treadmill 5 days/week, 30–60 min/day, with an intensity of 1.0 mile/hour over a 3-week period. Rats received an intravenous infusion of LPS after 24 hrs from the last training session. Elevated lavage tumor necrosis factor-alpha (TNF-α level in response to LPS was more marked in diabetic rats. HSP72 expression in lungs was significantly increased after exercise conditioning, but less pronounced in diabetic rats. After administration of LPS, exercised rats displayed higher survival rate as well as decreased lavage TNF-α level and lung edema in comparison to sedentary rats. Our findings suggest that exercise conditioning could attenuate the occurrence of inflammatory responses and lung damage, thereby reducing mortality rate in diabetic rats during endotoxemia.

  20. [Pulmonary apoptosis and necrosis in hyperoxia-induced acute mouse lung injury].

    Science.gov (United States)

    Zhang, Xiang-feng; Foda, Hussein D

    2004-07-01

    To investigate the pathways to cell death in hyperoxia-induced lung injury and the functional significance of apoptosis in vivo in response to hyperoxia. Seventy-two mice were exposed in sealed cages > 98% oxygen (for 24 - 72 h) or room air, and the severity of lung injury and epithelium sloughing was evaluated. The extent and location of apoptosis in injured lung tissues were studied by terminal transferase dUTP end labeling assay (TUNEL), reverse transcript-polymerase chain reaction (RT-PCR) and immunohistochemistry. Hyperoxia caused acute lung injury; the hyperoxic stress resulted in marked epithelium sloughing. TUNEL assay exhibited increased apoptosis index both in alveolar epithelial cells and bronchial epithelial cells in sections from mice after 48 h hyperoxia compared with their control group (0.51 +/- 0.10, 0.46 +/- 0.08 verse 0.04 +/- 0.02, 0.02 +/- 0.01). This was accompanied by increased expression of caspase-3 mRNA in lung tissues after 48 h hyperoxia compared with their control group (0.53 +/- 0.09 verse 0.34 +/- 0.07), the expression was higher at 72 h of hyperoxia (0.60 +/- 0.08). Immunohistochemistry study showed caspase-3 protein was located in cytoplasm and nuclei of airway epithelial cells, alveolar epithelial cells and macrophage in hyperoxia mice. The expression of caspase-3 protein in airway epithelium significantly increased at 24 h of hyperoxia compared with their control group (41.62 +/- 3.46 verse 15.86 +/- 1.84), the expression level was highest at 72 h of hyperoxia (55.24 +/- 6.80). Both apoptosis and necrosis contribute to cell death during hyperoxia. Apoptosis plays an important role in alveolar damage and cell death from hyperoxia.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Lung surfactant protein D (SP-D) response and regulation during acute and chronic lung injury.

    Science.gov (United States)

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F; Atochina-Vasserman, Elena N; Hansen, Soren

    2013-06-01

    Surfactant protein D (SP-D) is a collection that plays important roles in modulating host defense functions and maintaining phospholipid homeostasis in the lung. The aim of current study was to characterize comparatively the SP-D response in bronchoalveolar lavage (BAL) and serum in three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. In lipopolysaccharide-challenged mice, the level of SP-D in BAL increased within 6 h, peaked at 51 h (4,518 ng/ml), and returned to base level at 99 h (612 ng/ml). Serum levels of SP-D increased immediately (8.6 ng/ml), peaked at 51 h (16 ng/ml), and returned to base levels at 99 h (3.8 ng/ml). In a subacute bleomycin inflammation model, SP-D levels were 4,625 and 367 ng/ml in BAL and serum, respectively, 8 days after exposure. In a chronic Pc inflammation model, the highest level of SP-D was observed 6 weeks after inoculation, with BAL and serum levels of 1,868 and 335 ng/ml, respectively. We conclude that serum levels of SP-D increase during lung injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized systemically. The study also confirms the concept of using increased SP-D serum levels as a biomarker of especially chronic airway inflammation.

  6. 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

  7. [Organ damage and cardiorenal syndrome in acute heart failure].

    Science.gov (United States)

    Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

    2014-03-01

    Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  8. Association of Body Mass Index with Chromosome Damage Levels and Lung Cancer Risk among Males

    Science.gov (United States)

    Li, Xiaoliang; Bai, Yansen; Wang, Suhan; Nyamathira, Samuel Mwangi; Zhang, Xiao; Zhang, Wangzhen; Wang, Tian; Deng, Qifei; He, Meian; Zhang, Xiaomin; Wu, Tangchun; Guo, Huan

    2015-01-01

    Epidemiological studies have shown an etiological link between body mass index (BMI) and cancer risk, but evidence supporting these observations is limited. This study aimed to investigate potential associations of BMI with chromosome damage levels and lung cancer risk. First, we recruited 1333 male workers from a coke-oven plant to examine their chromosome damage levels; and then, a cohort study of 12 052 males was used to investigate the association of BMI with lung cancer incidence. We further carried out a meta-analysis for BMI and male lung cancer risk based on cohort studies. We found that men workers with excess body weight (BMI ≥ 25 kg/m2) had lower levels of MN frequencies than men with normal-weight (BMI: 18.5–24.9). Our cohort study indicated that, the relative risk (RR) for men with BMI ≥ 25 to develop lung cancer was 35% lower than RR for normal-weight men. Further meta-analysis showed that, compared to normal-weight men, men with BMI ≥ 25 had decreased risk of lung cancer among both the East-Asians and others populations. These results indicate that men with excess body weight had significant decreased chromosome damage levels and lower risk of lung cancer than those with normal-weight. However, further biological researches were needed to validate these associations. PMID:25820198

  9. 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.

  10. 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

  11. Allograft inflammatory factor-1 in the pathogenesis of bleomycin-induced acute lung injury.

    Science.gov (United States)

    Nagahara, Hidetake; Yamamoto, Aihiro; Seno, Takahiro; Obayashi, Hiroshi; Kida, Takashi; Nakabayashi, Amane; Kukida, Yuji; Fujioka, Kazuki; Fujii, Wataru; Murakami, Ken; Kohno, Masataka; Kawahito, Yutaka

    2016-02-01

    Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries of rats with an ectopic cardiac allograft. Some studies have shown that expression of AIF-1 increased in a mouse model of trinitrobenzene sulfonic acid-induced acute colitis and in acute cellular rejection of human cardiac allografts. These results suggest that AIF-1 is related to acute inflammation. The current study used bleomycin-induced acute lung injury to analyze the expression of AIF-1 and to examine its function in acute lung injury. Results showed that AIF-1 was significantly expressed in lung macrophages and increased in bronchoalveolar lavage fluid from mice with bleomycin-induced acute lung injury in comparison to control mice. Recombinant AIF-1 increased the production of IL-6 and TNF-α from RAW264.7 (a mouse macrophage cell line) and primary lung fibroblasts, and it also increased the production of KC (CXCL1) from lung fibroblasts. These results suggest that AIF-1 plays an important role in the mechanism underlying acute lung injury.

  12. 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

  13. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Science.gov (United States)

    Colombo, N.B.R.; Rangel, M.P.; Martins, V.; Hage, M.; Gelain, D.P.; Barbeiro, D.F.; Grisolia, C.K.; Parra, E.R.; Capelozzi, V.L.

    2015-01-01

    The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress. PMID:26200231

  14. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    N.B.R. Colombo

    2015-01-01

    Full Text Available The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

  15. Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury.

    Science.gov (United States)

    Aggarwal, Saurabh; Lam, Adam; Bolisetty, Subhashini; Carlisle, Matthew A; Traylor, Amie; Agarwal, Anupam; Matalon, Sadis

    2016-01-10

    Exposure to irritant gases, such as bromine (Br2), poses an environmental and occupational hazard that results in severe lung and systemic injury. However, the mechanism(s) of Br2 toxicity and the therapeutic responses required to mitigate lung damage are not known. Previously, it was demonstrated that Br2 upregulates the heme degrading enzyme, heme oxygenase-1 (HO-1). Since heme is a major inducer of HO-1, we determined whether an increase in heme and heme-dependent oxidative injury underlies the pathogenesis of Br2 toxicity. C57BL/6 mice were exposed to Br2 gas (600 ppm, 30 min) and returned to room air. Thirty minutes postexposure, mice were injected intraperitoneally with a single dose of the heme scavenging protein, hemopexin (Hx) (3 μg/gm body weight), or saline. Twenty-four hours postexposure, saline-treated mice had elevated total heme in bronchoalveolar lavage fluid (BALF) and plasma and acute lung injury (ALI) culminating in 80% mortality after 10 days. Hx treatment significantly lowered heme, decreased evidence of ALI (lower protein and inflammatory cells in BALF, lower lung wet-to-dry weight ratios, and decreased airway hyperreactivity to methacholine), and reduced mortality. In addition, Br2 caused more severe ALI and mortality in mice with HO-1 gene deletion (HO-1-/-) compared to wild-type controls, while transgenic mice overexpressing the human HO-1 gene (hHO-1) showed significant protection. This is the first study delineating the role of heme in ALI caused by Br2. The data suggest that attenuating heme may prove to be a useful adjuvant therapy to treat patients with ALI.

  16. DNA Damage of Lung Cells from Immature Cadmium-Ingested Mice

    Directory of Open Access Journals (Sweden)

    Xue-feng Yang

    2014-01-01

    Full Text Available The objective of this study was to investigate the effects of cadmium on DNA damage of lung cells in immature animals. Seventy-two immature mice were randomly divided into twelve cadmium-ingested groups including low dose (1/100 LD50, 1.87 mg/kg BW, middle dose (1/50 LD50, 3.74 mg/kg BW, high dose (1/25 LD50, 7.48 mg/kg BW and control group, and exposed to cadmium chloride for 10, 20 and 30 days, respectively. Mice were sacrificed after cadmium exposure for different time, and lung cells were collected to investigate DNA damage by comet assay. The results showed that comet tailing ratio, tail length, comet length, tail moment, Olive tail moment and damaged grade of lung cells from immature mice increased along with increasing of cadmium exposure dose and time. In low dose group treated for 30 days, there was significance (P<0.05 in comet length or high significance (P<0.01 in other parameters compared with control group or low dose group treated for 10 days. When mice were exposed to cadmium at high dose for 30 days, DNA of lung cells was damaged most seriously. Our results indicate that cadmium can induce DNA damage of lung cells from immature mice in dose- dependent and time-dependent manners, and DNA will be damaged when immature mice exposed to cadmium for long time even at low dose. Meanwhile, comet assay can be considered as a powerful and sensitive biomarker assay in risk assessment of immature animals exposed to cadmium.

  17. 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

  18. 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

  19. Effect of Contraction Velocity on Selected Muscle Damage Indices Following Acute Eccentric Exercise-Induced Muscle Damage: A Review

    Directory of Open Access Journals (Sweden)

    Farzaneh Movaseghi

    2016-12-01

    Full Text Available Background & Objective: Eccentric muscle action is mechanically more efficient but employs a unique activation strategy which predisposes the muscle to damage. Type II muscle fibers are more susceptible than type I fibers to muscle damage; hence, velocity probably interferes with mechanical stress and thus may modulate muscle damage. The purpose of this review study was to investigate the effect of contraction velocity on selected muscle damage indices following acute eccentric exercise-induced muscle damage. Material & Method: Looking up related articles published in valid scientific databases such as PubMed, Springer, Elsevier, Science Direct, and SID with standard keywords and according to the research criteria, 16 studies (1980 to 2015 were selected. Results: Ten studies showed that high velocity eccentric exercise induced greater muscle damage. Five studies showed no differences between velocities, and a single study indicated a greater magnitude of muscle damage following slow eccentric exercise. Conclusion: Thus, greater magnitude of damage is induced by contractions performed at a higher velocity. However, considering differences during tension in the majority of studies, focusing on elbow flexor muscles and muscle damage profile variety in various muscle groups, and more animal and human studies in other muscular groups are necessary to confirm how the velocity of acute eccentric exercise would affect the muscle damage.

  20. 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...

  1. Atomization method for verifying size effects of inhalable particles on lung damage of mice.

    Science.gov (United States)

    Tao, Chen; Tang, Yue; Zhang, Lan; Tian, Yonggang; Zhang, Yingmei

    2017-02-01

    To explore the size effects of inhalable particles on lung damage, aqueous aerosol containing cadmium was studied as a model to design a new type of two-stage atomization device that was composed of two adjustable parts with electronic ultrasonic atomization and pneumatic atomization. The working parameters and effectiveness of this device were tested with H2O atomization and CdCl2 inhalation, respectively. By gravimetrically detecting the mass concentrations of PM2.5 and PM10 and analysing the particle size with a laser sensor, we confirmed the particle size distribution of the aqueous aerosol produced by the new device under different working conditions. Then, we conducted experiments in male Kunming mice that inhaled CdCl2 to determine the size effects of inhalable particles on lung damage and to confirm the effectiveness of the device. The new device could effectively control the particle size in the aqueous aerosol. The inhaled CdCl2 entered and injured the lungs of the mice by causing tissue damage, oxidative stress, increasing endoplasmic reticulum stress and triggering an inflammatory response, which might be related to where the particles deposited. The smaller particles in the aqueous aerosol atomized by the new two-stage atomization device deposited deeper into lung causing more damage. This device could provide a new method for animal experiments involving inhalation with water-soluble toxins.

  2. 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.

  3. KGFR promotes Na+ channel expression in a rat acute lung injury ...

    African Journals Online (AJOL)

    KGFR promotes Na+ channel expression in a rat acute lung injury model. Binjian Liu1※ ... Recombinant adenovirus (AdEasy-KGFR) was injected via the tail vein. Expression of the ..... alternative for many protein replacement therapies, and.

  4. KGFR promotes Na+ channel expression in a rat acute lung injury ...

    African Journals Online (AJOL)

    KGFR promotes Na+ channel expression in a rat acute lung injury model. ... Recombinant adenovirus (AdEasy-KGFR) was injected via the tail vein. ... the three other groups; expression of these two genes in the injury adenovirus transduced ...

  5. 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.

  6. Damage of the auditory system associated with acute blast trauma.

    Science.gov (United States)

    Roberto, M; Hamernik, R P; Turrentine, G A

    1989-05-01

    This paper reviews the results of several studies on the effects of blast wave exposure on the auditory system of the chinchilla, the pig, and the sheep. The chinchillas were exposed at peak sound pressure levels of approximately 160 dB under well-controlled laboratory conditions. A modified shock tube was used to generate the blast waves. The pigs and sheep were exposed under field conditions in an instrumented hard-walled enclosure. Blast trauma was induced by the impact of a single explosive projectile. The peak sound pressure levels varied between 178 and 209 dB. All animals were killed immediately following exposure, and their temporal bones were removed for fixation and histologic analysis using light microscopy and scanning electron microscopy. Middle ears were examined visually for damage to the conductive system. There were well-defined differences in susceptibility to acoustic trauma among species. However, common findings in each species were the acute mechanical fracture and separation of the organ of Corti from the basilar membrane, and tympanic membrane and ossicular failure.

  7. 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.

  8. Effect of corticosteroid treatment on cell recovery by lung lavage in acute radiation-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Wesselius, L.J.; Floreani, A.A.; Kimler, B.F.; Papasian, C.J.; Dixon, A.Y. (Kansas City Veterans Administration Medical Center, MO (USA))

    1989-11-01

    The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.

  9. Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, T.P.; Heuser, V.D.; Tavares, P.; Leffa, D.D.; da Silva, G.A.; Citadini-Zanette, V.; Romao, P.R.T.; Pinho, R.A.; Streck, E.L.; Andrade,V.M. [University of Extremo Catarinense, Criciuma, SC (Brazil)

    2009-06-15

    We report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

  10. 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)

  11. 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...

  12. 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...

  13. Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles

    Directory of Open Access Journals (Sweden)

    Nemmar A

    2016-03-01

    Full Text Available Abderrahim Nemmar,1 Priya Yuvaraju,1 Sumaya Beegam,1 Javed Yasin,2 Elsadig E Kazzam,2 Badreldin H Ali3 1Department of Physiology, 2Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE; 3Department of Pharmacology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Al-Khoudh, Sultanate of Oman Abstract: The use of amorphous silica (SiO2 in biopharmaceutical and industrial fields can lead to human exposure by injection, skin penetration, ingestion, or inhalation. However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs on multiple organs and the mechanisms underlying these effects are not well understood. Presently, we investigated the acute (24 hours effects of intraperitoneally administered 50 nm SiNPs (0.25 mg/kg on systemic toxicity, oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney, and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the lung, liver, kidney, and brain, but was not changed in the heart. Similarly, superoxide dismutase and catalase activities were significantly affected by SiNPs in all organs studied. While the concentration of tumor necrosis factor α was insignificantly increased in the liver and brain, its increase was statistically significant in the lung, heart, and kidney. SiNPs induced a significant elevation in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver, and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed by comet assay, in all the organs studied. SiNPs caused leukocytosis and increased the plasma activities of lactate dehydrogenase, creatine kinase, alanine aminotranferase, and aspartate aminotransferase. These results indicate that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs, and highlight the need for thorough evaluation

  14. Lung damage and pulmonary uptake of serotonin in intact dogs

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.; Linehan, J.H.; Johnston, M.R.

    1985-06-01

    The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of (/sup 3/H)serotonin and the extravascular volume accessible to (/sup 14/C)antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.

  15. Suppression of lung inflammation in an LPS-induced acute lung injury model by the fruit hull of Gleditsia sinensis.

    Science.gov (United States)

    Kim, Kyun Ha; Kwun, Min Jung; Han, Chang Woo; Ha, Ki-Tae; Choi, Jun-Yong; Joo, Myungsoo

    2014-10-15

    The fruit hull of Gleditsia sinensis (FGS) used in traditional Asian medicine was reported to have a preventive effect on lung inflammation in an acute lung injury (ALI) mouse model. Here, we explored FGS as a possible therapeutics against inflammatory lung diseases including ALI, and examined an underlying mechanism for the effect of FGS. The decoction of FGS in water was prepared and fingerprinted. Mice received an intra-tracheal (i.t.) FGS 2 h after an intra-peritoneal (i.p.) injection of lipopolysaccharide (LPS). The effect of FGS on lung inflammation was determined by chest imaging of NF-κB reporter mice, counting inflammatory cells in bronchoalveolar lavage fluid, analyzing lung histology, and performing semi-quantitative RT-PCR analysis of lung tissue. Impact of Nrf2 on FGS effect was assessed by comparing Nrf2 knockout (KO) and wild type (WT) mice that were treated similarly. Bioluminescence from the chest of the reporter mice was progressively increased to a peak at 16 h after an i.p. LPS treatment. FGS treatment 2 h after LPS reduced the bioluminescence and the expression of pro-inflammatory cytokine genes in the lung. While suppressing the infiltration of inflammatory cells to the lungs of WT mice, FGS post-treatment failed to reduce lung inflammation in Nrf2 KO mice. FGS activated Nrf2 and induced Nrf2-dependent gene expression in mouse lung. FGS post-treatment suppressed lung inflammation in an LPS-induced ALI mouse model, which was mediated at least in part by Nrf2. Our results suggest a therapeutic potential of FGS on inflammatory lung diseases.

  16. 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

  17. Transfusion-related acute lung injury risk mitigation: an update.

    Science.gov (United States)

    Otrock, Z K; Liu, C; Grossman, B J

    2017-09-25

    Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion. Greater understanding of the pathophysiology of this syndrome has much improved during the last two decades. Plasma-containing components from female donors with leucocyte antibodies were responsible for the majority of TRALI fatalities before mitigation strategies were implemented. Over the past 15 years, measures to mitigate risk for TRALI have been implemented worldwide and they continued to evolve with time. The AABB requires that all plasma containing components and whole blood for transfusion must be collected from men, women who have not been pregnant, or women who have tested negative for human leucocyte antigen antibodies. Although the incidence of TRALI has decreased following the institution of TRALI mitigation strategies, TRALI is still the most common cause of transfusion-associated death in the United States. In this review, we focus on TRALI risk mitigation strategies. We describe the measures taken by blood collection facilities to reduce the risk of TRALI in the United States, Canada and European countries. We also review the literature for the effectiveness of these measures. © 2017 International Society of Blood Transfusion.

  18. 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.

  19. 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

  20. Transcriptional alterations of ET-1 axis and DNA damage in lung tissue of a rat obesity model.

    Science.gov (United States)

    Del Ry, Silvia; Cabiati, Manuela; Salvadori, Costanza; Guiducci, Letizia; Caselli, Chiara; Prescimone, Tommaso; Facioni, Maria Sole; Azzarà, Alessia; Chiaramonte, Anna; Mazzoni, Stefano; Bruschi, Fabrizio; Giannessi, Daniela; Scarpato, Roberto

    2015-03-01

    Obesity has been implicated in the development of many cancers. This can lead to genome damage, especially in the form of double-strand break, the presence of which is now easily detected through nuclear phosphorylation of histone H2AX (γ-H2AX) focus assay. Recently, the endothelin (ET) axis has also been shown to have a role in the growth and progression of several tumors, including lung cancer. The aim of this study was to evaluate the ET-1 system transcriptional alterations and γ-H2AX in lung tissue of Zucker rats subdivided into obese (O, n=22) and controls (CO, n=18) rats: under either fasting conditions (CO(fc)-O(fc)) or acute hyperglycemia (CO(AH)-O(AH)). Significantly higher prepro-ET-1 (p=0.05) and ET-converting enzyme (ECE)-2 mRNA expression was observed in O with respect to CO. A significant positive association was observed between prepro-ET-1 and ET-A in the whole rat population (p=0.009) or in the obese group alone (p=0.007). The levels of γ-H2AX in O and in O(AH) rats were significantly higher (p=0.019) than in the corresponding CO and CO(AH) rats (p=0.038). The study shows an inappropriate secretion of ET-1 in O animals with a parallel DNA damage in their lungs, providing novel mechanisms by which ET receptor antagonist may exert organ protection.

  1. Experimental evaluation of a new system for laser tissue welding applied on damaged lungs.

    Science.gov (United States)

    Schiavon, Marco; Marulli, Giuseppe; Zuin, Andrea; Lunardi, Francesca; Villoresi, Paolo; Bonora, Stefano; Calabrese, Fiorella; Rea, Federico

    2013-05-01

    Alveolar air leaks represent a challenging problem in thoracic surgery, leading to increased patient morbidity and prolonged hospitalization. Several methods have been used, but no ideal technique exists yet. We investigated the lung-sealing capacity of an experimental kit for laser tissue welding. The kit is composed of a semiconductor laser system applied on a protein substrate associated with a chromophore that increases absorption. In vitro tests on porcine lung tissue were done to define ideal laser parameters (power 100 Å, frequency 50 Hz, pulse duration 400 µs) and protein substrate dilution (50%). For in vivo tests, through a left thoracotomy, 14 pigs received two different lung damages: a linear incision and a circular incision. Protein substrate applied on damaged areas was treated with laser to obtain a layer that reconstituted the integrity of the visceral pleura. Air leaks were intraoperatively evaluated by water submersion test with an airway pressure of 20 cmH2O. Animals were sacrificed at postoperative days 0 and 7 to study early and late pathological features. After applying laser treatment, no air leaks were seen in all proofs except in 2 cases in which a second application was required. At time 0, pathological damage mostly consisted of superficial alveolar necrotic tissue covered by protein membrane. At time 7, a complete recovery of lung lesions by fibrous scar with slight inflammatory reaction of adjacent lung tissue was seen. This experimental study demonstrated the effectiveness of laser tissue welding applied to seal air leaks after lung surgery. Further studies are needed to verify acceptability for human application.

  2. 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.

  3. 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.

  4. Oxidative DNA damage is involved in cigarette smoke-induced lung injury in rats.

    Science.gov (United States)

    Chen, Zhihai; Wang, Dapeng; Liu, Xing; Pei, Weiwei; Li, Jianxiang; Cao, Yi; Zhang, Jie; An, Yan; Nie, Jihua; Tong, Jian

    2015-09-01

    Reactive oxygen species (ROS) induced by exogenous toxicants are suggested to be involved in carcinogenesis by oxidative modification of DNA. 8-Hydroxyl-2-deoxyguanosine (8-OHdG) has been considered as a reliable biomarker for oxidative DNA damage both in vivo and in vitro studies. But the effect of smoking on oxidative damage has not yet been fully elucidated. Wistar rats were exposed to cigarette smoke at concentrations of 20 and 60 % for 30 min, twice/day for 45 weeks. Then the histopathology of lung tissues, levels of ROS, 8-OHdG, and total antioxidant (T-AOC), expression of DNA repair enzymes, e.g. 8-oxyguaine DNA glycosylase (OGG1), and MutThomolog 1 (Oxidized Purine Nucleoside Triphosphatase, MTH1) were determined in urine, peripheral blood lymphocytes, and lung tissue. The results showed that long-term cigarette smoke exposure can cause obvious damages of lung tissue in rats. In addition, a significant and cigarette smoke concentration-dependent increase in ROS and 8-OHdG were observed compared with the non-exposed control rats. In contrast, the expression of OGG1 and MTH1, and T-AOC levels were obviously decreased after long-term exposure to cigarette smoke. These findings indicate that long-term exposure to cigarette smoker increases ROS levels, decreases total antioxidant capacity, and interferes DNA repair capacity that eventually induces oxidative DNA damage, which appears to play an important role in cigarette smoke-induced lung injury in rats, and determination of 8-OHdG levels might be a useful method for monitoring oxidative damage in cigarette smokers.

  5. 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

  6. 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.

  7. The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model

    Directory of Open Access Journals (Sweden)

    Pirofski Liise-Anne

    2007-01-01

    Full Text Available Abstract Background Intranasal inoculation of Streptococcus pneumoniae D39 serotype 2 causes fatal pneumonia in mice. The cytotoxic and inflammatory properties of pneumolysin (PLY have been implicated in the pathogenesis of pneumococcal pneumonia. Methods To examine the role of PLY in this experimental model we performed ELISA assays for PLY quantification. The distribution patterns of PLY and apoptosis were established by immunohistochemical detection of PLY, caspase-9 activity and TUNEL assay on tissue sections from mice lungs at various times, and the results were quantified with image analysis. Inflammatory and apoptotic cells were also quantified on lung tissue sections from antibody treated mice. Results In bronchoalveolar lavages (BAL, total PLY was found at sublytic concentrations which were located in alveolar macrophages and leukocytes. The bronchoalveolar epithelium was PLY-positive, while the vascular endothelium was not PLY reactive. The pattern and extension of cellular apoptosis was similar. Anti-PLY antibody treatment decreased the lung damage and the number of apoptotic and inflammatory cells in lung tissues. Conclusion The data strongly suggest that in vivo lung injury could be due to the pro-apoptotic and pro-inflammatory activity of PLY, rather than its cytotoxic activity. PLY at sublytic concentrations induces lethal inflammation in lung tissues and is involved in host cell apoptosis, whose effects are important to pathogen survival.

  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. Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

    Science.gov (United States)

    Kip, Gülay; Çelik, Ali; Bilge, Mustafa; Alkan, Metin; Kiraz, Hasan Ali; Özer, Abdullah; Şıvgın, Volkan; Erdem, Özlem; Arslan, Mustafa; Kavutçu, Mustafa

    2015-01-01

    Objective Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R). Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods Diabetes was induced with streptozotocin (55 mg/kg) in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC), diabetes plus ischaemia-reperfusion (DIR), and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD)) after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg); the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group) in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT) and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA) levels were evaluated in the lung tissues of all rats. Results Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively). The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively). The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT activity

  12. Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

    Directory of Open Access Journals (Sweden)

    Gülay Kip

    2015-09-01

    Full Text Available Objective: Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R. Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods: Diabetes was induced with streptozotocin (55 mg/kg in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC, diabetes plus ischaemia-reperfusion (DIR, and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg; the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA levels were evaluated in the lung tissues of all rats. Results: Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively. The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively. The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT

  13. C-peptide attenuates acute lung inflammation in a murine model of hemorrhagic shock and resuscitation by reducing gut injury.

    Science.gov (United States)

    Kao, Raymond L C; Xu, Xuemei; Xenocostas, Anargyros; Parry, Neil; Mele, Tina; Martin, Claudio M; Rui, Tao

    2017-08-01

    The study aims to evaluate whether C-peptide can reduce gut injury during hemorrhagic shock (HS) and resuscitation (R) therefore attenuate shock-induced inflammation and subsequent acute lung injury. Twelve-week-old male mice (C57/BL6) were hemorrhaged (mean arterial blood pressure maintained at 35 mm Hg for 60 minutes) and then resuscitated with Ringer's lactate, followed by red blood cell transfusion with (HS/R) or without C-peptide (HS/R + C-peptide). Mouse gut permeability, bacterial translocation into the circulatory system and intestinal pathology, circulating HMGB1, and acute lung injury were assessed at different times after R. The mice in the control group underwent sham procedures without HS. Compared to the sham group, the mice in the HS/R group showed increased gut permeability (6.07 ± 3.41 μg of FD4/mL) and bacterial translocation into the circulatory system (10.05 ± 4.92, lipopolysaccharide [LPS] of pg/mL), and increased gut damage; conversely, mice in the HS/R + C-peptide group showed significantly reduced gut permeability (1.59 ± 1.39 μg of FD4/mL; p C-peptide group showed decreased HMGB1 (7.27 ± 1.93 ng/mL; p C-peptide exerts beneficial effects to attenuate gut injury and dysfunction, therefore diminishing lung inflammation and subsequent injury in mice with HS and R.

  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. The Effects of Quercetin on Acute Lung Injury and Biomarkers of Inflammation and Oxidative Stress in the Rat Model of Sepsis.

    Science.gov (United States)

    Gerin, Fethullah; Sener, Umit; Erman, Hayriye; Yilmaz, Ahsen; Aydin, Bayram; Armutcu, Ferah; Gurel, Ahmet

    2016-04-01

    Experimental studies indicate that sepsis causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative damage, and inflammation on lung injury, following sepsis model by cecal ligation and puncture, and the effects of quercetin, antioxidant, and anti-inflammatory flavonoid, in the lung tissue were investigated. In the present study, we found that administration of single-dose quercetin before cecal ligation and puncture procedure, while markedly diminishing the levels of YKL-40 and oxidant molecules (xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA)), increases the antioxidant enzymes levels. Quercetin is beneficial to acute lung injury by decreasing the levels of oxidative stress markers and increasing the antioxidant enzyme activities. Quercetin also causes a decrease in the serum levels of YKL-40 and periostin in the oxidative lung injury induced by the experimental sepsis model.

  16. Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin).

    Science.gov (United States)

    Pini, Alessandro; Boccalini, Giulia; Lucarini, Laura; Catarinicchia, Stefano; Guasti, Daniele; Masini, Emanuela; Bani, Daniele; Nistri, Silvia

    2016-06-01

    Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD), which is characterized by airway remodeling, lung inflammation and fibrosis, emphysema, and respiratory failure. The current therapies can improve COPD management but cannot arrest its progression and reduce mortality. Hence, there is a major interest in identifying molecules susceptible of development into new drugs to prevent or reduce CS-induced lung injury. Serelaxin (RLX), or recombinant human relaxin-2, is a promising candidate because of its anti-inflammatory and antifibrotic properties highlighted in lung disease models. Here, we used a guinea pig model of CS-induced lung inflammation, and remodeling reproducing some of the hallmarks of COPD. Animals exposed chronically to CS (8 weeks) were treated with vehicle or RLX, delivered by osmotic pumps (1 or 10 μg/day) or aerosol (10 μg/ml/day) during CS treatment. Controls were nonsmoking animals. RLX maintained airway compliance to a control-like pattern, likely because of its capability to counteract lung inflammation and bronchial remodeling. In fact, treatment of CS-exposed animals with RLX reduced the inflammatory recruitment of leukocytes, accompanied by a significant reduction of the release of proinflammatory cytokines (tumor necrosis factor α and interleukin-1β). Moreover, RLX was able to counteract the adverse bronchial remodeling and emphysema induced by CS exposure by reducing goblet cell hyperplasia, smooth muscle thickening, and fibrosis. Of note, RLX delivered by aerosol has shown a comparable efficacy to systemic administration in reducing CS-induced lung dysfunction and damage. In conclusion, RLX emerges as a new molecule to counteract CS-induced inflammatory lung diseases.

  17. Acute Respiratory Distress Syndrome Caused by Leukemic Infiltration of the Lung

    Directory of Open Access Journals (Sweden)

    Yao-Kuang Wu

    2008-05-01

    Full Text Available Respiratory distress syndrome resulting from leukemic pulmonary infiltrates is seldom diagnosed antemortem. Two 60- and 80-year-old women presented with general malaise, progressive shortness of breath, and hyperleukocytosis, which progressed to acute respiratory distress syndrome (ARDS after admission. Acute leukemia with pulmonary infection was initially diagnosed, but subsequent examinations including open lung biopsy revealed leukemic pulmonary infiltrates without infection. In one case, the clinical condition and chest radiography improved initially after combination therapy with chemotherapy for leukemia and aggressive pulmonary support. However, new pulmonary infiltration on chest radiography and hypoxemia recurred, which was consistent with acute lysis pneumopathy. Despite aggressive treatment, both patients died due to rapidly deteriorating condition. Leukemic pulmonary involvement should be considered in acute leukemia patients with non-infectious diffusive lung infiltration, especially in acute leukemia with a high blast count.

  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. Neutrophil elastase causes tissue damage that decreases host tolerance to lung infection with burkholderia species.

    Directory of Open Access Journals (Sweden)

    Manoranjan Sahoo

    2014-08-01

    Full Text Available Two distinct defense strategies can protect the host from infection: resistance is the ability to destroy the infectious agent, and tolerance is the ability to withstand infection by minimizing the negative impact it has on the host's health without directly affecting pathogen burden. Burkholderia pseudomallei is a Gram-negative bacterium that infects macrophages and causes melioidosis. We have recently shown that inflammasome-triggered pyroptosis and IL-18 are equally important for resistance to B. pseudomallei, whereas IL-1β is deleterious. Here we show that the detrimental role of IL-1β during infection with B. pseudomallei (and closely related B. thailandensis is due to excessive recruitment of neutrophils to the lung and consequent tissue damage. Mice deficient in the potentially damaging enzyme neutrophil elastase were less susceptible than the wild type C57BL/6J mice to infection, although the bacterial burdens in organs and the extent of inflammation were comparable between C57BL/6J and elastase-deficient mice. In contrast, lung tissue damage and vascular leakage were drastically reduced in elastase-deficient mice compared to controls. Bradykinin levels were higher in C57BL/6 than in elastase-deficient mice; administration of a bradykinin antagonist protected mice from infection, suggesting that increased vascular permeability mediated by bradykinin is one of the mechanisms through which elastase decreases host tolerance to melioidosis. Collectively, these results demonstrate that absence of neutrophil elastase increases host tolerance, rather than resistance, to infection by minimizing host tissue damage.

  20. Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine

    Science.gov (United States)

    2011-07-01

    Decay-Accelerating Factor Mitigates Controlled Hemorrhage- Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine Jurandir J. Dalle...DAF treatment improved hemorrhage- induced hyperkalemia . The protective effects of DAF appear to be related to its ability to reduce tissue complement...Decay-accelerating factor mitigates controlled hemorrhage-instigated intestinal and lung tissue damage and hyperkalemia in swine 5a. CONTRACT NUMBER

  1. 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.

  2. Corticosteroids prevent acute lung dysfunction caused by thoracic irradiation in unanesthetized sheep

    Energy Technology Data Exchange (ETDEWEB)

    Loyd, J.E.; Bolds, J.M.; Wickersham, N.; Malcolm, A.W.; Brigham, K.L.

    1988-11-01

    We sought to determine the effect of corticosteroid therapy in a new acute model of oxidant lung injury, thoracic irradiation in awake sheep. Sheep were irradiated with 1,500 rads to the whole chest except for blocking the heart and adjacent ventral lung. Seven experimental sheep were given methylprednisolone (1 g intravenously every 6 h for four doses) and thoracic irradiation; control sheep received only irradiation. In irradiated control sheep, lung lymph flow increased from baseline (7.6 ml/h) to peak at 3 h (13.2), and lung lymph protein clearance increased from 5.1 to 9.7 ml/h. Mean pulmonary artery pressure increased in the irradiated control sheep from 19 to 32.4 cm H/sub 2/O, whereas the lung lymph thromboxane concentration increased from 0.09 to 6.51 ng/ml at 3 h. Arterial oxygen tension in irradiated control sheep fell gradually from 86 mm Hg at baseline to 65 mm Hg at 8 h. Methylprednisolone administration significantly prevented the increase in lung lymph protein clearance, mean pulmonary artery pressure, and lung lymph thromboxane concentration. Methylprednisolone also prevented the fall in arterial oxygen tension after thoracic irradiation, but did not prevent a further decrease in lymphocytes in blood or lung lymph after radiation. We conclude that corticosteroid therapy prevents most of the acute physiologic changes caused by thoracic irradiation in awake sheep.

  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. 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

  6. Biomass burning in the Amazon region causes DNA damage and cell death in human lung cells.

    Science.gov (United States)

    de Oliveira Alves, Nilmara; Vessoni, Alexandre Teixeira; Quinet, Annabel; Fortunato, Rodrigo Soares; Kajitani, Gustavo Satoru; Peixoto, Milena Simões; Hacon, Sandra de Souza; Artaxo, Paulo; Saldiva, Paulo; Menck, Carlos Frederico Martins; Batistuzzo de Medeiros, Silvia Regina

    2017-09-07

    Most of the studies on air pollution focus on emissions from fossil fuel burning in urban centers. However, approximately half of the world's population is exposed to air pollution caused by biomass burning emissions. In the Brazilian Amazon population, over 10 million people are directly exposed to high levels of pollutants resulting from deforestation and agricultural fires. This work is the first study to present an integrated view of the effects of inhalable particles present in emissions of biomass burning. Exposing human lung cells to particulate matter smaller than 10 µm (PM10), significantly increased the level of reactive oxygen species (ROS), inflammatory cytokines, autophagy, and DNA damage. Continued PM10 exposure activated apoptosis and necrosis. Interestingly, retene, a polycyclic aromatic hydrocarbon present in PM10, is a potential compound for the effects of PM10, causing DNA damage and cell death. The PM10 concentrations observed during Amazon biomass burning were sufficient to induce severe adverse effects in human lung cells. Our study provides new data that will help elucidate the mechanism of PM10-mediated lung cancer development. In addition, the results of this study support the establishment of new guidelines for human health protection in regions strongly impacted by biomass burning.

  7. 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

  8. 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

  9. 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

  10. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

    Science.gov (United States)

    Jin, Shunying; Merchant, Michael L; Ritzenthaler, Jeffrey D; McLeish, Kenneth R; Lederer, Eleanor D; Torres-Gonzalez, Edilson; Fraig, Mostafa; Barati, Michelle T; Lentsch, Alex B; Roman, Jesse; Klein, Jon B; Rane, Madhavi J

    2015-01-01

    Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a

  11. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

    Directory of Open Access Journals (Sweden)

    Shunying Jin

    Full Text Available Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC deposition-induced acute lung injury (ALI. Components of gamma amino butyric acid (GABA signaling, including GABA B receptor 2 (GABABR2, GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP, in the bronchoalveolar lavage fluid (BALF. Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting

  12. Inhibition of the mitochondrial respiratory chain function abrogates quartz induced DNA damage in lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Li Hui [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Haberzettl, Petra [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Albrecht, Catrin [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Hoehr, Doris [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Knaapen, Ad M. [Department of Health Risk Analysis and Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), University of Maastricht (Netherlands); Borm, Paul J.A. [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Hogeschool Zuyd Heerlen (Netherlands); Schins, Roel P.F. [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany)]. E-mail: roel.schins@uni-duesseldorf.de

    2007-04-01

    Respirable quartz dust has been classified as a human carcinogen by the International Agency for Research on Cancer. The aim of our study was to investigate the mechanisms of DNA damage by DQ12 quartz in RLE-6TN rat lung epithelial type II cells (RLE). Transmission electron microscopy and flow-cytometry analysis showed a rapid particle uptake (30 min to 4 h) of quartz by the RLE cells, but particles were not found within the cell nuclei. This suggests that DNA strand breakage and induction of 8-hydroxydeoxyguanosine - as also observed in these cells during these treatment intervals - did not result from direct physical interactions between particles and DNA, or from short-lived particle surface-derived reactive oxygen species. DNA damage by quartz was significantly reduced in the presence of the mitochondrial inhibitors rotenone and antimycin-A. In the absence of quartz, these inhibitors did not affect DNA damage, but they reduced cellular oxygen consumption. No signs of apoptosis were observed by quartz. Flow-cytometry analysis indicated that the reduced DNA damage by rotenone was not due to a possible mitochondria-mediated reduction of particle uptake by the RLE cells. Further proof of concept for the role of mitochondria was shown by the failure of quartz to elicit DNA damage in mitochondria-depleted 143B (rho-0) osteosarcoma cells, at concentrations where it elicited DNA damage in the parental 143B cell line. In conclusion, our data show that respirable quartz particles can elicit oxidative DNA damage in vitro without entering the nuclei of type II cells, which are considered to be important target cells in quartz carcinogenesis. Furthermore, our observations indicate that such indirect DNA damage involves the mitochondrial electron transport chain function, by an as-yet-to-be elucidated mechanism.

  13. 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

  14. 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.

  15. Recovery rate and prognosis in older persons who develop acute lung injury and the acute respiratory distress syndrome.

    Science.gov (United States)

    Ely, E Wesley; Wheeler, Arthur P; Thompson, B Taylor; Ancukiewicz, Marek; Steinberg, Kenneth P; Bernard, Gordon R

    2002-01-01

    The incidence of acute respiratory failure requiring mechanical ventilation increases 10-fold from the ages of 55 to 85 years, yet the rate of recovery and outcomes in older persons who develop acute lung injury are poorly defined. To examine age as an independent risk factor in recovery and intensive care unit discharge after acute lung injury. Prospective cohort study. 10 U.S. university-based medical centers. 902 mechanically ventilated patients enrolled in randomized, controlled trials for the treatment of acute lung injury. All patients were managed according to a standardized protocol for ventilator management and weaning. Frequency and time to achieve well-defined recovery landmarks, duration of ventilation and intensive care unit stay, and survival. Median duration of mechanical ventilation was 19 days (interquartile range, 7 to >28 days) for patients 70 years of age or older (n = 173) compared with 10 days (interquartile range, 5 to 26 days) for patients younger than 70 years of age (n = 729) (P 28 days) and 16 days for the younger group (8 to >28 days) (P = 0.004). Survival rates decreased across increasing decades of age (P 0.2). After passing a spontaneous breathing trial, however, older patients required 1 more day than younger patients to achieve unassisted breathing (P = 0.002) and 3 more days to leave the intensive care unit (P = 0.005). In a multivariable Cox proportional hazards analysis, age of 70 years or older was a strong predictor of in-hospital death (hazard ratio, 2.5 [95% CI, 2.0 to 3.2]; P acute lung injury compared with their younger counterparts, even after adjustment for covariates. Older survivors recovered from respiratory failure and achieved spontaneous breathing at the same rate as younger patients but had greater difficulty achieving liberation from the ventilator and being discharged from the intensive care unit.

  16. The effects of anesthetics and misonidazole on the development of radiation-induced lung damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Down, J.D. (Inst. of Cancer Research, Surrey, England); Collis, C.H.; Jeffery, P.K.; Steel, G.G.

    1983-02-01

    The measurement of breathing frequency as a functional end-point of radiation-induced lung injury in mice allowed two phases of damage to be discerned; the first was manifest at 12-20 weeks after irradiation, the second beyond 28 weeks. Anesthesia by pentobarbitone sodium or steroids gave significant radioprotection of the lung during the early pneumonitic phase. Addition of the hypoxic cell sensitizer misonidazole removed the protective influence of the anesthetics but did not sensitize the lungs of unanesthetized mice. No anesthetic protection was detected for the late response, showing evidence for dissociation between early and late lung damage. The degree of epilation was measured on the dorsal thoracic region of the same mice. Protection by anesthetics and its reversal by misonidazole was also demonstrated. These results provide a warning of potential hazards in the laboratory evaluation of chemical radiosensitizers. The use of anesthetics at the time of irradiation could lead to an exaggerated enhancement of normal tissue damage.

  17. 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...

  18. 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

  19. GADD45a promoter regulation by a functional genetic variant associated with acute lung injury.

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    Sumegha Mitra

    Full Text Available RATIONALE: Growth arrest DNA damage inducible alpha (GADD45a is a stress-induced gene we have shown to participate in the pathophysiology of ventilator-induced lung injury (VILI via regulation of mechanical stress-induced Akt ubiquitination and phosphorylation. The regulation of GADD45a expression by mechanical stress and its relationship with acute lung injury (ALI susceptibility and severity, however, remains unknown. OBJECTIVES: We examined mechanical stress-dependent regulatory elements (MSRE in the GADD45a promoter and the contribution of promoter polymorphisms in GADD45a expression and ALI susceptibility. METHODS AND RESULTS: Initial studies in GADD45a knockout and heterozygous mice confirmed the relationship of GADD45a gene dose to VILI severity. Human lung endothelial cells (EC transfected with a luciferase vector containing the full length GADD45a promoter sequence (-771 to +223 demonstrated a >4 fold increase in GADD45a expression in response to 18% cyclic stretch (CS, 4 h compared to static controls while specific promoter regions harboring CS-dependent MSRE were identified using vectors containing serial deletion constructs of the GADD45a promoter. In silico analyses of GADD45a promoter region (-371 to -133 revealed a potential binding site for specificity protein 1 (SP1, a finding supported by confirmed SP1 binding with the GADD45a promoter and by the significant attenuation of CS-dependent GADD45a promoter activity in response to SP1 silencing. Separately, case-control association studies revealed a significant association of a GADD45a promoter SNP at -589 (rs581000, G>C with reduced ALI susceptibility. Subsequently, we found allelic variation of this SNP is associated with both differential GADD45a expression in mechanically stressed EC (18% CS, 4 h and differential binding site of interferon regulatory factor 7 (IRF7 at this site. CONCLUSION: These results strongly support a functional role for GADD45a in ALI/VILI and identify a

  20. 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. Copyright © 2016 the American Physiological Society.

  1. 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.

  2. Genetic Deletion and Pharmacological Inhibition of PI3Kγ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease

    Directory of Open Access Journals (Sweden)

    Maria Galluzzo

    2015-01-01

    Full Text Available Purpose. Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF. Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti-inflammatory drugs have shown several limits. PI3Kγ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kγ on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods. βENaC overexpressing mice (βENaC-Tg were backcrossed with PI3Kγ-deficient (PI3KγKO mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF. Furthermore, we assessed the effect of a specific PI3Kγ inhibitor (AS-605240 on inflammatory cell number in BALF. Results. Genetic deletion of PI3Kγ decreased neutrophil numbers in BALF of PI3KγKO/βENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3Kγ inhibitor AS-605240 decreased the number of neutrophils in BALF of βENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions. These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3Kγ in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo.

  3. A numerical model of the respiratory modulation of pulmonary shunt and PaO2 oscillations for acute lung injury.

    Science.gov (United States)

    Beda, Alessandro; Jandre, Frederico C; Giannella-Neto, Antonio

    2010-03-01

    It is an accepted hypothesis that the amplitude of the respiratory-related oscillations of arterial partial pressure of oxygen (DeltaPaO2) is primarily modulated by fluctuations of pulmonary shunt (Deltas), the latter generated mainly by cyclic alveolar collapse/reopening, when present. A better understanding of the relationship between DeltaPaO2, Deltas, and cyclic alveolar collapse/reopening can have clinical relevance for minimizing the severe lung damage that the latter can cause, for example during mechanical ventilation (MV) of patients with acute lung injury (ALI). To this aim, we numerically simulated the effect of such a relationship on an animal model of ALI under MV, using a combination of a model of lung gas exchange during tidal ventilation with a model of time dependence of shunt on alveolar collapse/opening. The results showed that: (a) the model could adequately replicate published experimental results regarding the complex dependence of DeltaPaO2 on respiratory frequency, driving pressure (DeltaP), and positive end-expiratory pressure (PEEP), while simpler models could not; (b) such a replication strongly depends on the value of the model parameters, especially of the speed of alveolar collapse/reopening; (c) the relationship between DeltaPaO2 and Deltas was overall markedly nonlinear, but approximately linear for PEEP>or=6 cmH2O, with very large DeltaPaO2 associated with relatively small Deltas.

  4. 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.

  5. Nicotine overrides DNA damage-induced G1/S restriction in lung cells.

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    Takashi Nishioka

    Full Text Available As an addictive substance, nicotine has been suggested to facilitate pro-survival activities (such as anchorage-independent growth or angiogenesis and the establishment of drug resistance to anticancer therapy. Tobacco smoking consists of a variety of carcinogens [such as benzopyrene (BP and nitrosamine derivatives] that are able to cause DNA double strand breaks. However, the effect of nicotine on DNA damage-induced checkpoint response induced by genotoxins remains unknown. In this study, we investigated the events occurred during G(1 arrest induced by γ-radiation or BP in nicotine-treated murine or human lung epithelial cells. DNA synthesis was rapidly inhibited after exposure to γ-radiation or BP treatment, accompanied with the activation of DNA damage checkpoint. When these cells were co-treated with nicotine, the growth restriction was compromised, manifested by upregulation of cyclin D and A, and attenuation of Chk2 phosphorylation. Knockdown of cyclin D or Chk2 by the siRNAs blocked nicotine-mediated effect on DNA damage checkpoint activation. However, nicotine treatment appeared to play no role in nocodazole-induced mitotic checkpoint activation. Overall, our study presented a novel observation, in which nicotine is able to override DNA damage checkpoint activated by tobacco-related carcinogen BP or γ-irradiation. The results not only indicates the potentially important role of nicotine in facilitating the establishment of genetic instability to promote lung tumorigenesis, but also warrants a dismal prognosis for cancer patients who are smokers, heavily exposed second-hand smokers or nicotine users.

  6. 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...

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome

    Science.gov (United States)

    Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F.; An, Gary

    2013-06-01

    Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

  13. Experimental Study on the Mechanism of Protective Effect of Free Fu on Gut-derived Endotoxin-Mediated Lung Damage

    Institute of Scientific and Technical Information of China (English)

    李道本; 杨胜兰; 陈瑞

    2004-01-01

    The effect of tumor necrosis factor-α (TNF-α) on endotoxin (ET)-mediated lung damage caused by incomplete ligation of large intestine and the influence of free Fu on the expression of TNF-α mRNA were explored. Forty SD rats were randomly divided into 4 groups: normal control group, model group, ligation group and treatment group (n=10 in each group). The models were made by the method of partly ligating the rectum outside the body. The plasma level of lipopolysaccaride was measured by dynamic nephelo metric method and the serum level of TNF-α was detected by the method of radioactive immunity. The expression of TNF-α mRNA in lung tissue was detected by RT-PCR method. The results were compared among the 4 groups. The results showed the plasma levels of ET and serum TNF-α in the model group and the expression of TNF-α mRNA in the lung tissues were remarkably higher than those in the normal control group (P<0.01). After the treatment of free Fu, all of the above indexes in the treatment group were all decreased as compared with model group (all P<0.01), and the damage to lung was alleviated. It was concluded that TNF-α might play a very important role in the ET-mediated lung damage caused by incomplete ligation of large intestine, free Fu could protect the lung from damage.

  14. 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.

  15. Video-Assisted Thoracoscopic Lung Biopsy as a Possible Cause of Acute Interstitial Pneumonia in a Patient with Nonspecific Interstitial Pneumonia

    Directory of Open Access Journals (Sweden)

    D Jeffrey Moore

    2004-01-01

    Full Text Available The present case report describes a 44-year-old woman who presented with dyspnea due to diffuse interstitial lung disease. High-resolution computed tomography showed features of usual interstitial pneumonia, but the lung biopsy obtained by video-assisted thoracoscopy was consistent with a histological pattern of nonspecific interstitial pneumonia. Following the procedure, the patient developed progressive respiratory distress and died on postoperative day 13 with a clinical picture of acute interstitial pneumonia. The autopsy showed evidence of diffuse alveolar damage superimposed on the background pattern of nonspecific interstitial pneumonia. The present case report supports the notion that patients with a variety of subtypes of idiopathic interstitial pneumonias may be at risk of exacerbation of their underlying disease following thoracic procedures, including video-assisted thoracoscopic lung biopsy.

  16. P21-PARP-1 Pathway Is Involved in Cigarette Smoke-Induced Lung DNA Damage and Cellular Senescence

    Science.gov (United States)

    Yao, Hongwei; Sundar, Isaac K.; Gorbunova, Vera; Rahman, Irfan

    2013-01-01

    Persistent DNA damage triggers cellular senescence, which may play an important role in the pathogenesis of cigarette smoke (CS)-induced lung diseases. Both p21CDKN1A (p21) and poly(ADP-ribose) polymerase-1 (PARP-1) are involved in DNA damage and repair. However, the role of p21-PARP-1 axis in regulating CS-induced lung DNA damage and cellular senescence remains unknown. We hypothesized that CS causes DNA damage and cellular senescence through a p21-PARP-1 axis. To test this hypothesis, we determined the levels of γH2AX (a marker for DNA double-strand breaks) as well as non-homologous end joining proteins (Ku70 and Ku80) in lungs of mice exposed to CS. We found that the level of γH2AX was increased, whereas the level of Ku70 was reduced in lungs of CS-exposed mice. Furthermore, p21 deletion reduced the level of γH2AX, but augmented the levels of Ku70, Ku80, and PAR in lungs by CS. Administration of PARP-1 inhibitor 3-aminobenzamide increased CS-induced DNA damage, but lowered the levels of Ku70 and Ku80, in lungs of p21 knockout mice. Moreover, 3-aminobenzamide increased senescence-associated β-galactosidase activity, but decreased the expression of proliferating cell nuclear antigen in mouse lungs in response to CS. Interestingly, 3-aminobenzamide treatment had no effect on neutrophil influx into bronchoalveolar lavage fluid by CS. These results demonstrate that the p21-PARP-1 pathway is involved in CS-induced DNA damage and cellular senescence. PMID:24244594

  17. P21-PARP-1 pathway is involved in cigarette smoke-induced lung DNA damage and cellular senescence.

    Directory of Open Access Journals (Sweden)

    Hongwei Yao

    Full Text Available Persistent DNA damage triggers cellular senescence, which may play an important role in the pathogenesis of cigarette smoke (CS-induced lung diseases. Both p21(CDKN1A (p21 and poly(ADP-ribose polymerase-1 (PARP-1 are involved in DNA damage and repair. However, the role of p21-PARP-1 axis in regulating CS-induced lung DNA damage and cellular senescence remains unknown. We hypothesized that CS causes DNA damage and cellular senescence through a p21-PARP-1 axis. To test this hypothesis, we determined the levels of γH2AX (a marker for DNA double-strand breaks as well as non-homologous end joining proteins (Ku70 and Ku80 in lungs of mice exposed to CS. We found that the level of γH2AX was increased, whereas the level of Ku70 was reduced in lungs of CS-exposed mice. Furthermore, p21 deletion reduced the level of γH2AX, but augmented the levels of Ku70, Ku80, and PAR in lungs by CS. Administration of PARP-1 inhibitor 3-aminobenzamide increased CS-induced DNA damage, but lowered the levels of Ku70 and Ku80, in lungs of p21 knockout mice. Moreover, 3-aminobenzamide increased senescence-associated β-galactosidase activity, but decreased the expression of proliferating cell nuclear antigen in mouse lungs in response to CS. Interestingly, 3-aminobenzamide treatment had no effect on neutrophil influx into bronchoalveolar lavage fluid by CS. These results demonstrate that the p21-PARP-1 pathway is involved in CS-induced DNA damage and cellular senescence.

  18. Flecainide Improve Sepsis Induced Acute Lung Injury by Controlling Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Jia Song

    2016-08-01

    Full Text Available Background: Flecainide is an antiarrhythmic agent that is used primarily in the treatment of cardiac arrhythmias. Some evidences also suggest that flecainide can participate in alveolar fluid clearance and inflammatory responses. This experiment was aimed to evaluate the effects of flecainide on sepsis induced acute lung injury in a rat model. Methods: Rats were treated with subcutaneous infusion of saline or flecainide (0.1 or 0.2 mg/kg/hr by a mini-osmotic pump. Subcutaneous infusion was started 3 hours before and continued until 8 hours after intraperitoneal injection of saline or endotoxin. Animals were sacrificed for analyses of severity of acute lung injury with wet to dry (W/D ratio and lung injury score (LIS in lung and inflammatory responses with level of leukocyte, polymorphonuclear neutrophils (PMNs and inteleukin-8 (IL-8 in bronchoalveolar lavages fluid (BALF. Results: Flecainide markedly improved dose dependently sepsis induced acute lung injury as analysed by W/D ratio (from 2.24 ± 0.11 to 1.76 ± 0.09, p < 0.05 and LIS (from 3 to 1, p < 0.05, and inflammatory response as determined by leukocyte (from 443 ± 127 to 229 ± 95, p < 0.05, PMNs (from 41.43 ± 17.63 to 2.43 ± 2.61, p < 0.05 and IL-8 (from 95.00 ± 15.28 to 40.00 ± 10.21, p < 0.05 in BALF. Conclusions: Flecanide improve sepsis induced acute lung injury in rats by controlling inflammatory responses.

  19. Inflammatory potential of the spores of Penicillium spinulosum isolated from indoor air of a moisture-damaged building in mouse lungs.

    Science.gov (United States)

    Jussila, Juha; Komulainen, Hannu; Kosma, Veli-Matti; Pelkonen, Jukka; Hirvonen, Maija-Riitta

    2002-10-01

    Excess moisture and microbial growth have been associated with adverse health effects, especially in the airways, of the inhabitants of moisture-damaged buildings. The spores of Penicillium spp. are commonly present in the indoor air, both in moisture-damaged and in reference buildings, though their numbers seem to be significantly higher in the damaged buildings. To assess the potential of Penicillium spinulosum to evoke harmful respiratory effects, mice were exposed via intratracheal instillation to a single dose of the spores of P. spinulosum, isolated from the indoor air of a moisture-damaged building (1×10(5), 1×10(6), 5×10(6), 1×10(7) or 5×10(7) spores). Inflammation and toxicity in lungs were evaluated 24 h later. The time-course of the effects was investigated with the dose of 5×10(6) spores for 28 days. The fungal spores caused mild transient inflammation. The spore exposure transiently increased proinflammatory cytokine (TNFα and IL-6) levels in bronchoalveolar lavage fluid (BALF) in a dose- and time-dependent manner. The highest concentrations of both cytokines were measured at 6 h after a single dosage. The spore exposure did not cause expression of inducible nitric oxide synthase in lavaged cells. Neutrophils were acutely recruited into airways, but the response leveled off in 3 days. Neither cytotoxicity nor major changes in vascular permeability (i.e. increases in albumin, total protein, lactate dehydrogenase or hemoglobin levels in BALF) were observed in the lungs. Considering the profile and magnitude of the changes and the dose of the spores, we conclude that P. spinulosum has a low potential to cause acute respiratory inflammation, nor does it cause direct cytotoxicity.

  20. Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose.

    Science.gov (United States)

    Collis, C. H.; Wilson, C. M.; Jones, J. M.

    1980-01-01

    Cycylphosphamide (Cy) produces an interstitial pneumonitis in CBA mice. The extent of the lung damage has been quantified by measuring the increase in ventilation rate over 6 weeks after an i.p. injection of Cy 200, 250 and 300 mg/kg. A dose-dependent response was found. When a preliminary ("priming") dose of Cy at 50 mg/kg was given 7, 9 or 14 days before a single large dose of 250 mg/kg, lung damage was reduced, as shown by a smaller increase in ventilation rate than in those receiving 250 mg/kg alone, and this difference was significant (P less than 0.01) in the Day-14-and highly significant (P<0.001) in the Day-7-"primed" groups. When primed less than 7 days before, there was a relative increase in ventilation rate, which was statistically significant (P less than 0.01) in the Day-1-primed group. Similar effects were also seen in the survival of the mice. PMID:7426315

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children.

    Science.gov (United States)

    López-Fernández, Yolanda; Azagra, Amelia Martínez-de; de la Oliva, Pedro; Modesto, Vicent; Sánchez, Juan I; Parrilla, Julio; Arroyo, María José; Reyes, Susana Beatriz; Pons-Ódena, Martí; López-Herce, Jesús; Fernández, Rosa Lidia; Kacmarek, Robert M; Villar, Jesús

    2012-12-01

    The incidence and outcome of the acute respiratory distress syndrome in children are not well-known, especially under current ventilatory practices. The goal of this study was to determine the incidence, etiology, and outcome of acute respiratory distress syndrome in the pediatric population in the setting of lung protective ventilation. A 1-yr, prospective, multicenter, observational study in 12 geographical areas of Spain (serving a population of 3.77 million ≤ 15 yrs of age) covered by 21 pediatric intensive care units. All consecutive pediatric patients receiving invasive mechanical ventilation and meeting American-European Consensus Criteria for acute respiratory distress syndrome. None. Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 146 mechanically ventilated patients fulfilled the acute respiratory distress syndrome definition, representing a incidence of 3.9/100,000 population ≤ 15 yrs of age/yr. Pneumonia and sepsis were the most common causes of acute respiratory distress syndrome. At the time of meeting acute respiratory distress syndrome criteria, mean PaO2/FIO2 was 99 mm Hg ± 41 mm Hg, mean tidal volume was 7.6 mL/kg ± 1.8 mL/kg predicted body weight, mean plateau pressure was 27 cm H2O ± 6 cm H2O, and mean positive end-expiratory pressure was 8.9 cm ± 2.9 cm H2O. Overall pediatric intensive care unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and 27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the assessment of oxygenation under standard ventilatory settings, 118 (80.8%) patients continued to meet acute respiratory distress syndrome criteria (PaO2/FIO2 104 mm Hg ± 36 mm Hg; pediatric intensive care units mortality 30.5%), whereas 28 patients (19.2%) had a PaO2/FIO2 >200 mm Hg (pediatric intensive care units mortality 7.1%) (p = .014). This is the largest study to estimate prospectively the pediatric population-based acute

  6. 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.

  7. Sympathoadrenal activation and endothelial damage in patients with varying degrees of acute infectious disease

    DEFF Research Database (Denmark)

    Ostrowski, Sisse Rye; Gaïni, Shahin; Pedersen, Court;

    2015-01-01

    PURPOSE: To investigate levels, associations between, and predictive value of plasma catecholamines and biomarkers of endothelial damage in patients with acute infectious illness stratified according to infection type and sepsis severity. MATERIAL AND METHODS: This is a post hoc study of plasma s...

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Protection of Total Flavonoid Fraction from Nervilia fordii on Lipopolysaccharide-induced Acute Lung Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    HUANG Ming-qing; XIE You-liang; LAI Xiao-ping; LIN Ling; XU Yin-ji; LU Jin-jian; CHEN Xiu-ping

    2012-01-01

    Objective To investigate the effects of total flavonoid fraction(TFF)from Nervilia fordii on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in rats,and to explore their protective mechanism.Methods LPS-induced ALI model was established by LPS(5 mg/kg)injection via left cervical vein.Blood samples were collected from the cervical artery of all rats at 5 and 6 h after LPS challenge for arterial blood gas test and cytokines measurements,and pulmonary microvascular permeability(PMP),lung wet/dry weight ratio(W/D),and pathological features were observed.Results Phytochemical study showed that the TFF contained 67.3% of flavonoids expressed in rutin and three flavone glycosides.The TFF pretreatment(6.24 and 12.48 mg/kg)attenuated the partial arterial pressure of oxygen decline in blood significantly,and decreased the PMP and lung W/D in ALI rats.In addition,the TFF(6.24 and 12.48 mg/kg)also ameliorated the LPS-induced lung damages including alveolar edema,neutrophils infiltration,alveolar hemorrhage,and thickening of the alveolar wall.Furthermore,the treatment with the TFF(6.24 and 12.48 mg/kg)also down-regulated the levels of pro-inflammatory cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and intercellular adhesion molecule-1(ICAM-1),and up-regulated the level of anti-inflammatory cytokine IL-10 in serum of ALI rats simultaneously.Conclusion These results suggest that the TFF could protect LPS-induced ALI in rats,which may be mediated,at least in part,by adjusting the production of inflammatory cytokines including TNF-α,IL-6,ICAM-1,and IL-10.

  13. A genetic mouse model to investigate hyperoxic acute lung injury survival.

    Science.gov (United States)

    Prows, Daniel R; Hafertepen, Amanda P; Gibbons, William J; Winterberg, Abby V; Nick, Todd G

    2007-08-20

    Acute lung injury (ALI) is a devastating disease that maintains a high mortality rate, despite decades of research. Hyperoxia, a universal treatment for ALI and other critically ill patients, can itself cause pulmonary damage, which drastically restricts its therapeutic potential. We stipulate that having the ability to use higher levels of supplemental O2 for longer periods would improve recovery rates. Toward this goal, a mouse model was sought to identify genes contributing to hyperoxic ALI (HALI) mortality. Eighteen inbred mouse strains were screened in continuous >95% O2. A significant survival difference was identified between sensitive C57BL/6J and resistant 129X1/SvJ strains. Although resistant, only one-fourth of 129X1/SvJ mice survived longer than any C57BL/6J mouse, demonstrating decreased penetrance of resistance. A survival time difference between reciprocal F1 mice implicated a parent-of-origin (imprinting) effect. To further evaluate imprinting and begin to delineate the genetic components of HALI survival, we generated and phenotyped offspring from all four possible intercrosses. Segregation analysis supported maternal inheritance of one or more genes but paternal inheritance of one or more contributor genes. A significant sex effect was demonstrated, with males more resistant than females for all F2 crosses. Survival time ranges and sensitive-to-resistant ratios of the different F2 crosses also supported imprinting and predicted that increased survival is due to dominant resistance alleles contributed by both the resistant and sensitive parental strains. HALI survival is multigenic with a complex mode of inheritance, which should be amenable to genetic dissection with this mouse model.

  14. 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.

  15. Propagation prevention: a complementary mechanism for "lung protective" ventilation in acute respiratory distress syndrome.

    Science.gov (United States)

    Marini, John J; Gattinoni, Luciano

    2008-12-01

    To describe the clinical implications of an often neglected mechanism through which localized acute lung injury may be propagated and intensified. Experimental and clinical evidence from the medical literature relevant to the airway propagation hypothesis and its consequences. The diffuse injury that characterizes acute respiratory distress syndrome is often considered a process that begins synchronously throughout the lung, mediated by inhaled or blood-borne noxious agents. Relatively little attention has been paid to possibility that inflammatory lung injury may also begin focally and propagate sequentially via the airway network, proceeding mouth-ward from distal to proximal. Were this true, modifications of ventilatory pattern and position aimed at geographic containment of the injury process could help prevent its generalization and limit disease severity. The purposes of this communication are to call attention to this seldom considered mechanism for extending lung injury that might further justify implementation of low tidal volume/high positive end-expiratory pressure ventilatory strategies for lung protection and to suggest additional therapeutic measures implied by this broadened conceptual paradigm.

  16. 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.

  17. 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.

  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. Application of the adductome approach to assess intertissue DNA damage variations in human lung and esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Kanaly, Robert A. [Department of Technology and Ecology, Graduate School of Global Environmental Studies, Kyoto University, Kyoto 606-8501 (Japan); Department of Environmental Biosciences, International Graduate School of Arts and Sciences, Yokohama City University, Yokohama 236-0027 (Japan); Matsui, Saburo [Department of Technology and Ecology, Graduate School of Global Environmental Studies, Kyoto University, Kyoto 606-8501 (Japan); Hanaoka, Tomoyuki [Epidemiology and Prevention Division, National Cancer Center Research Institute, Tokyo 104-0045 (Japan); Matsuda, Tomonari [Department of Technology and Ecology, Graduate School of Global Environmental Studies, Kyoto University, Kyoto 606-8501 (Japan)], E-mail: matsuda@z05.mbox.media.kyoto-u.ac.jp

    2007-12-01

    Methods for determining the differential susceptibility of human organs to DNA damage have not yet been explored to any large extent due to technical constraints. The development of comprehensive analytical approaches by which to detect intertissue variations in DNA damage susceptibility may advance our understanding of the roles of DNA adducts in cancer etiology and as exposure biomarkers at least. A strategy designed for the detection and comparison of multiple DNA adducts from different tissue samples was applied to assess esophageal and peripherally- and centrally-located lung tissue DNA obtained from the same person. This adductome approach utilized LC/ESI-MS/MS analysis methods designed to detect the neutral loss of 2'-deoxyribose from positively ionized 2'-deoxynucleoside adducts transmitting the [M+H]{sup +} > [M+H-116]{sup +} transition over 374 transitions. In the final analyses, adductome maps were produced which facilitated the visualization of putative DNA adducts and their relative levels of occurrence and allowed for comprehensive comparisons between samples, including a calf thymus DNA negative control. The largest putative adducts were distributed similarly across the samples, however, differences in the relative amounts of putative adducts in lung and esophagus tissue were also revealed. The largest-occurring lung tissue DNA putative adducts were 90% similar (n = 50), while putative adducts in esophagus tissue DNA were shown to be 80 and 84% similar to central and peripheral lung tissue DNA respectively. Seven DNA adducts, N{sup 2}-ethyl-2'-deoxyguanosine (N{sup 2}-ethyl-dG), 1,N{sup 6}-etheno-2'-deoxyadenosine ({epsilon}dA), {alpha}-S- and {alpha}-R-methyl-{gamma}-hydroxy-1,N{sup 2}-propano-2'-deoxyguanosine (1,N{sup 2}-PdG{sub 1}, 1,N{sup 2}-PdG{sub 2}), 3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro-8-hydroxy-pyrimido[1,2-a] purine-(3H)-one (8-OH-PdG) and the two stereoisomers of 3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro

  20. 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.

  1. [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.

  2. 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

  3. Differential evaluation of bronchoalveolar lavage cells and leukotrienes in unilateral acute lung injury and ARDS patients.

    Science.gov (United States)

    Antonelli, M; Lenti, L; Bufi, M; De Blasi, R A; Vivino, G; Conti, G; Pelaia, P; Zicari, A; Pontieri, G; Gasparetto, A

    1989-01-01

    Patients with unilateral acute lung injury (UALI; n = 6) and ARDS (n = 4) were evaluated by bronchoalveolar lavage, as controls we used 5 patients suffering from cerebral hemorrhage and without pulmonary, cardiac or infectious disease who were mechanically ventilated. For each group of patients two independent bronchoalveolar lavages (BAL) were performed. The BAL fluid recovered from the two lungs was immediately analyzed for leukotrienes (LTS) by means of RP-HPLC and stained for cell counts. The BAL from the control group did not show any LTS and the percentage of neutrophils was within the normal range: 1 +/- 0.2% right lung and 1.2 +/- 0.4% left lung. The BAL fluid from UALI patients showed two different patterns, the injured lung showed high levels of LTS (39.1 +/- 8 ng ml-1 LTB4; 25 +/- 6 ng ml-1 LTD4 and 27.8 +/- 8.2 ng ml-1 11-trans LTC4) and an increased percentage of neutrophils (74.2 +/- 7%) compared to controls. Only 2 out of the 6 patients from the UALI group showed small amounts of LTB4 (4 ng ml-1) and LTD4 (3.2 ng ml-1). The BAL obtained from the "healthy lung" in both cases showed values of LTS almost eight fold lower than those present in the injured lung. The percentage of neutrophils from the unaffected lungs (4.3 +/- 7%) was not significantly different from controls. Lavage fluid from ARDS patients showed a similar picture to that of the affected lung from UALI patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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    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

  5. Protective effect of N-acetylcysteine on lung dendritic cells against damage in multiple organ dysfunction syndrome model

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    Hong-wei WANG

    2012-10-01

    Full Text Available Objective To explore the protective effect of N-acetylcysteine (NAC on lung dendritic cells (DCs from damage in multiple organ dysfunction syndrome (MODS mouse model. Methods Animal model of MODS was established by injecting zymosan into the peritoneal cavity of BALB/c mice, and the mice were thereafter randomly divided into zymosan group, zymosan + NAC group and control group, 20 for each. MPO activity in lung tissue was measured by biochemical analysis 48 hours after modeling. Pathological changes of the lung were observed under light microscope. Lung DCs were separated by density gradient centrifugation and CD11c+ immunomagnetic beads. DCs' phenotypes of MHC-Ⅱ/ⅠAd and CD86 were analyzed by flow cytometry. Apoptosis of DCs was detected by flow cytometry with double labeling of Annexin V and 7-AAD. Results Compared with control group, the MPO activity in lung tissue remarkably increased in zymosan group (P lt; 0.05. Infiltration by a large number of neutrophilic granulocytes was found in lungs, suggesting serious injuries in lung. The expressions of MHC-Ⅱ/Ⅰ-Ad and CD86 on DC surface and the percentage of DC apoptosis increased dramatically (P lt; 0.05. Compared with zymosan group, the MPO activity remarkably declined and the lung injury was mitigatory (P lt; 0.05; the number of infiltrating neutrophilic granulocytes decreased greatly, and the expressions of MHC-Ⅱ/Ⅰ-Ad and CD86 on the DC surface and the percentage of DC apoptosis decreased dramatically (P lt; 0.05 in zymosan + NAC group. Conclusion NAC in vivo could inhibit DC activation-induced apoptosis and relieve lung injury, thus being of protective effect on lung DCs against damage in MODS model.

  6. 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

  7. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus L., protects rat tissues against oxidative damage after acute ethanol administration

    Directory of Open Access Journals (Sweden)

    Carmen Pinto

    2014-01-01

    Full Text Available Ethanol-mediated free radical generation is directly involved in alcoholic liver disease. In addition, chronic alcohol bingeing also induces pathological changes and dysfunction in multi-organs. In the present study, the protective effect of xanthohumol (XN on ethanol-induced damage was evaluated by determining antioxidative parameters and stress oxidative markers in liver, kidney, lung, heart and brain of rats. An acute treatment (4 g/kg b.w. of ethanol resulted in the depletion of superoxide dismutase, catalase and glutathione S-transferase activities and reduced glutathione content. This effect was accompanied by the increased activity of tissue damage marker enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase and a significant increase in lipid peroxidation and hydrogen peroxide concentrations. Pre-treatment with XN protected rat tissues from ethanol-induced oxidative imbalance and partially mitigated the levels to nearly normal levels in all tissues checked. This effect was dose dependent, suggesting that XN reduces stress oxidative and protects rat tissues from alcohol-induced injury.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Kai-Zong Li; Ke-Feng Dou

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor á (TNFα) antibody on pancreatic encephalopathy in rats.METHODS:One hundred and twenty SD rats were randomly divided into normal control group,acute necrotizing pancreatitis group and TNFα antibody treated group.Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct.Serum TNFα was detected and animals were killed 12 h after drug administration.Changes in content of brain water,MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.RESULTS:In TNFα antibody treated group,serum TNFálevel was decreased.Content of brain water,MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05).CONCLUSION:TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.

  13. Environmental Pollutant Ozone Causes Damage to Lung Surfactant Protein B (SP-B)

    Science.gov (United States)

    2015-01-01

    Lung surfactant protein B (SP-B) is an essential protein found in the surfactant fluid at the air–water interface of the lung. Exposure to the air pollutant ozone could potentially damage SP-B and lead to respiratory distress. We have studied two peptides, one consisting of the N-terminus of SP-B [SP-B(1–25)] and the other a construct of the N- and C-termini of SP-B [SP-B(1–25,63–78)], called SMB. Exposure to dilute levels of ozone (∼2 ppm) of monolayers of each peptide at the air–water interface leads to a rapid reaction, which is evident from an increase in the surface tension. Fluorescence experiments revealed that this increase in surface tension is accompanied by a loss of fluorescence from the tryptophan residue at the interface. Neutron and X-ray reflectivity experiments show that, in contrast to suggestions in the literature, the peptides are not solubilized upon oxidation but rather remain at the interface with little change in their hydration. Analysis of the product material reveals that no cleavage of the peptides occurs, but a more hydrophobic product is slowly formed together with an increased level of oligomerization. We attributed this to partial unfolding of the peptides. Experiments conducted in the presence of phospholipids reveal that the presence of the lipids does not prevent oxidation of the peptides. Our results strongly suggest that exposure to low levels of ozone gas will damage SP-B, leading to a change in its structure. The implication is that the oxidized protein will be impaired in its ability to interact at the air–water interface with negatively charged phosphoglycerol lipids, thus compromising what is thought to be its main biological function. PMID:26270023

  14. Quantification of radiation-induced lung damage with CT scans - The possible benefit for radiogenomics

    Energy Technology Data Exchange (ETDEWEB)

    De Ruysscher, Dirk [Radiation Oncology, Univ. Hospitals Leuven/KU Leuven, Leuven (Belgium); Dept. of Radiation Oncology (Maastro clinic), Maastricht Univ. Medical Center, Maastricht (Netherlands)], e-mail: dirk.deruysscher@uzleuven.be; Sharifi, Hoda [Dept. of Radiation Oncology (Maastro clinic), Maastricht Univ. Medical Center, Maastricht (Netherlands); Defraene, Gilles [Radiation Oncology, Univ. Hospitals Leuven/KU Leuven, Leuven (Belgium)] [and others

    2013-10-15

    Background: Radiation-induced lung damage (RILD) is an important problem. Although physical parameters such as the mean lung dose are used in clinical practice, they are not suited for individualised radiotherapy. Objective, quantitative measurements of RILD on a continuous instead of on an ordinal, semi-quantitative, semi-subjective scale, are needed. Methods: Hounsfield unit (HU) changes before versus three months post-radiotherapy were correlated per voxel with the radiotherapy dose in 95 lung cancer patients. Deformable registration was used to register pre- and post-CT scans and the density increase was quantified for various dose bins. The dose-response curve for increased HU was quantified using the slope of a linear regression (HU/Gy). The end-point for the toxicity analysis was dyspnoea = grade 2. Results: Radiation dose was linearly correlated with the change in HU (mean R2 = 0.74 {+-} 0.28). No differences in HU/Gy between groups treated with stereotactic radiotherapy, conventional radiotherapy alone, sequential or concurrent chemo-radiotherapy were observed. In the whole patient group, 33/95 (34.7%) had dyspnoea {>=} G2. Of the 48 patients with a HU/Gy below the median, 16 (33.3%) developed dyspnoea = G2, while in the 47 patients with a HU/Gy above the median, 17 (36.1%) had dyspnoea {>=}G2 (not significant). Individual patients showed a nearly 21-fold difference in radiosensitivity, with HU/Gy ranging from 0 to 10 HU/Gy. Conclusions: HU changes identify objectively the whole range of individual radiosensitivity on a continuous, quantitative scale. CT density changes may allow more robust and accurate radiogenomics studies.

  15. Quantification of Lung Damage in an Elastase-Induced Mouse Model of Emphysema

    Directory of Open Access Journals (Sweden)

    Arrate Muñoz-Barrutia

    2012-01-01

    Full Text Available Objective. To define the sensitivity of microcomputed tomography- (micro-CT- derived descriptors for the quantification of lung damage caused by elastase instillation. Materials and Methods. The lungs of 30 elastase treated and 30 control A/J mice were analyzed 1, 6, 12, and 24 hours and 7 and 17 days after elastase instillation using (i breath-hold-gated micro-CT, (ii pulmonary function tests (PFTs, (iii RT-PCR for RNA cytokine expression, and (iv histomorphometry. For the latter, an automatic, parallel software toolset was implemented that computes the airspace enlargement descriptors: mean linear intercept (Lm and weighted means of airspace diameters (D0, D1, and D2. A Support Vector Classifier was trained and tested based on three nonhistological descriptors using D2 as ground truth. Results. D2 detected statistically significant differences (P<0.01 between the groups at all time points. Furthermore, D2 at 1 hour (24 hours was significantly lower (P<0.01 than D2 at 24 hours (7 days. The classifier trained on the micro-CT-derived descriptors achieves an area under the curve (AUC of 0.95 well above the others (PFTS AUC = 0.71; cytokine AUC = 0.88. Conclusion. Micro-CT-derived descriptors are more sensitive than the other methods compared, to detect in vivo early signs of the disease.

  16. 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...

  17. [Diagnostic imaging in acute pulmonary embolism. The use of spiral computed tomography, lung scintigraphy and echocardiography].

    Science.gov (United States)

    Hess, Søren; Madsen, Poul Henning; Jørgensen, Henrik Boel; Høilund-Carlsen, Poul Flemming

    2005-10-10

    Acute pulmonary embolism is an underdiagnosed and potentially lethal condition. Treatment may be lifesaving but is associated with severe side effects. Thus, reliable diagnostic imaging is essential. We conducted a literature review on the use of spiral computed tomography, lung scintigraphy and echocardiography in acute pulmonary embolism and identified 562 articles, of which 16 original papers met our inclusion criteria. From these, we concluded that none of the modalities is applicable in every situation. Spiral computed tomography can confirm the diagnosis but cannot rule out subsegmental embolism. With lung scintigraphy, perfusion imaging alone is probably sufficient and suited to both confirming and ruling out the diagnosis. Echocardiography should be reserved for patients with an emergent need for treatment and cannot rule out the diagnosis.

  18. Cytoprotective roles of GSH, SOD and solcoseryl against ischemic damage and reperfusion injury to warm ischemic lung. Study of Canine warm ischemic lung.

    OpenAIRE

    Taniguchi, Hideki; Kawahara, Katsunobu; Nakasone, Tomonori; Ikari, Hideki; Honjoh, Seiji; Hisano, Hiroshi; Takahashi, Takao; Kusano, Hiroyuki; Ayabe, Hiroyoshi; Tomita, Masao

    1990-01-01

    This study was performed to clarify the roles of reduced glutathion (GSH), superoxide dismutase (SOD), and solcosaryl in ischemic damage and reperfusion injury to the warm ischemic lungs of experimental animals. Fifty-one warm ischemic canine lungs were made by hilar stripping and clamping of the left PA, PV and bronchus for 2-3 hours. In the Non-perfusion group, GSH (50mg/ kg, I. V.: Group II) and solcoseryl (50mg/kg, I. V.: Group III) were administered. In the perfusion group, Euro-Collins ...

  19. 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.

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

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    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.

  2. Potential role of Saudi red propolis in alleviating lung damage induced by methicillin resistant Staphylococcus aureus virulence in rats.

    Science.gov (United States)

    Saddiq, Amna Ali; Mohamed, Azza Mostafa

    2016-07-01

    The aim of this study was to explore the protective impact of aqueous extract of Saudi red propolis against rat lung damage induced by the pathogenic bacteria namely methicillin resistant Staphylococcus aureus (MRSA) ATCC 6538 strain. Infected rats were received a single intraperitoneal (i.p.) injection of bacterial suspension at a dose of 1 X 10(6) CFU / 100g body weight. Results showed that oral administration of an aqueous extract of propolis (50mg/100g body weight) daily for two weeks to infected rats simultaneously with bacterial infection, effectively ameliorated the alteration of oxidative stress biomarker, malondialdehyde (MDA), as well as the antioxidant markers, glutathione peroxidase (GPx) and superoxide dismutase (SOD), in lungs of infected rats compared with infected untreated ones. Also, the used propolis extract successfully modulated the alterations in proinflammatory mediators, tumor necrosis factor-α (TNF- α) and vascular endothelial growth factor (VEGF) in serum. In addition, the propolis extract successfully modulated the oxidative DNA damage and the apoptosis biomarker, caspase 3, in lungs of S aureus infected rats compared with infected untreated animals. The biochemical results were supported by histo-pathological observation of lung tissues. In conclusion, the beneficial prophylactic role of the aqueous extract of Saudi red propolis against lung damage induced by methicillin resistant S aureus may be related to the antioxidant, anti-inflammatory, immunomodulatory and antiapoptosis of its active constituents.

  3. 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.

  4. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Science.gov (United States)

    He, Xiaolin; Han, Bing; Mura, Marco; Li, Li; Cypel, Marcelo; Soderman, Avery; Picha, Kristen; Yang, Jing; Liu, Mingyao

    2008-01-30

    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. 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. 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.

  5. 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...

  6. 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

  7. DIVALENT METAL TRANSPORTER-1 REGULATION BY IRON AND VANADIUM MODULATES HYDROGEN PEROXIDE-INDUCED DNA DAMAGE IN LUNG CELLS

    Science.gov (United States)

    The divalent metal transporter-1 (DMT1) participates in the detoxification of metals that can damage lung epithelium. Elevated iron levels increase the expression of DMT1 in bronchial epithelial cells stimulating its uptake and storage in ferritin, thus making iron unavailable t...

  8. Lung damage in mice after inhalation of nanofilm spray products: the role of perfluorination and free hydroxyl groups

    DEFF Research Database (Denmark)

    Nørgaard, Asger W; Larsen, Søren T.; Hammer, Maria;

    2010-01-01

    Exposures to two commercial nanofilm spray products (NFPs), a floor sealant (NFP 1) and a coating product for tiles (NFP 2), were investigated for airway irritation, airway inflammation, and lung damage in a mouse inhalation model. The particle exposure was characterized by particle number, parti...... groups in the silanes/alkylsiloxanes was also critical for the toxicity....

  9. Dissociation of DNA damage and mitochondrial injury caused by hydrogen peroxide in SV-40 transformed lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Adcock Ian M

    2002-11-01

    Full Text Available Abstract Background Since lung epithelial cells are constantly being exposed to reactive oxygen intermediates (ROIs, the alveolar surface is a major site of oxidative stress, and each cell type may respond differently to oxidative stress. We compared the extent of oxidative DNA damage with that of mitochondrial injury in lung epithelial cells at the single cell level. Result DNA damage and mitochondrial injury were measured after oxidative stress in the SV-40 transformed lung epithelial cell line challenged with hydrogen peroxide (H2O2. Single cell analysis of DNA damage was determined by assessing the number of 8-oxo-2-deoxyguanosine (8-oxo-dG positive cells, a marker of DNA modification, and the length of a comet tail. Mitochondrial membrane potential, ΔΨm, was determined using JC-1. A 1 h pulse of H2O2 induced small amounts of apoptosis (3%. 8-oxo-dG-positive cells and the length of the comet tail increased within 1 h of exposure to H2O2. The number of cells with reduced ΔΨm increased after the addition of H2O2 in a concentration-dependent manner. In spite of a continual loss of ΔΨm, DNA fragmentation was reduced 2 h after exposure to H2O2. Conclusion The data suggest that SV-40 transformed lung epithelial cells are resistant to oxidative stress, showing that DNA damage can be dissociated from mitochondrial injury.

  10. 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.

  11. 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.

  12. 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.

  13. Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage.

    Science.gov (United States)

    García-Beccaria, María; Martínez, Paula; Méndez-Pertuz, Marinela; Martínez, Sonia; Blanco-Aparicio, Carmen; Cañamero, Marta; Mulero, Francisca; Ambrogio, Chiara; Flores, Juana M; Megias, Diego; Barbacid, Mariano; Pastor, Joaquín; Blasco, Maria A

    2015-07-01

    Telomeres are considered anti-cancer targets, as telomere maintenance above a minimum length is necessary for cancer growth. Telomerase abrogation in cancer-prone mouse models, however, only decreased tumor growth after several mouse generations when telomeres reach a critically short length, and this effect was lost upon p53 mutation. Here, we address whether induction of telomere uncapping by inhibition of the TRF1 shelterin protein can effectively block cancer growth independently of telomere length. We show that genetic Trf1 ablation impairs the growth of p53-null K-Ras(G12V)-induced lung carcinomas and increases mouse survival independently of telomere length. This is accompanied by induction of telomeric DNA damage, apoptosis, decreased proliferation, and G2 arrest. Long-term whole-body Trf1 deletion in adult mice did not impact on mouse survival and viability, although some mice showed a moderately decreased cellularity in bone marrow and blood. Importantly, inhibition of TRF1 binding to telomeres by small molecules blocks the growth of already established lung carcinomas without affecting mouse survival or tissue function. Thus, induction of acute telomere uncapping emerges as a potential new therapeutic target for lung cancer.

  14. 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

  15. 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.

  16. Ukrain (NSC 631570) ameliorates intestinal ischemia-reperfusion-induced acute lung injury by reducing oxidative stress

    Science.gov (United States)

    Kocak, Cengiz; Kocak, Fatma Emel; Akcilar, Raziye; Akcilar, Aydin; Savran, Bircan; Zeren, Sezgin; Bayhan, Zulfu; Bayat, Zeynep

    2016-01-01

    Intestinal ischemia-reperfusion (I/R) causes severe destruction in remote organs. Lung damage is a frequently seen complication after intestinal I/R. Ukrain (NSC 631570) is a synthetic thiophosphate derivative of alkaloids from the extract of the celandine (Chelidonium majus L.) plant. We investigated the effect of Ukrain in animals with lung injury induced by intestinal I/R. Adult male Spraque-Dawley rats were randomly divided into four groups: control, Ukrain, I/R, I/R with Ukrain. Before intestinal I/R was induced, Ukrain was administered intraperitoneally at a dose of 7.0 mg/body weight. After 1 h ischemia and 2 h reperfusion period, lung tissues were excised. Tissue levels of total oxidative status (TOS), total antioxidant status (TAS) were measured and oxidative stress indices (OSI) were calculated. Lung tissues were also examined histopathologically. TOS and OSI levels markedly increased and TAS levels decreased in the I/R group compared to the control group (P < 0.05). TOS and OSI levels markedly decreased and TAS levels increased in the I/R with Ukrain group compared with the group subjected to IR only (P < 0.05). Severe hemorrhage, alveolar septal thickening, and leukocyte infiltration were observed in the I/R group. In the I/R with Ukrain group, morphologic changes occurring as a result of lung damage attenuated and histopathological scores reduced compared to the I/R group (P < 0.05). Our results suggest that Ukrain pretreatment could reduce lung injury induced by intestinal I/R induced via anti-inflammatory and antioxidant effects. PMID:26773189

  17. Ukrain (NSC 631570 ameliorates intestinal ischemia-reperfusion-induced acute lung injury by reducing oxidative stress

    Directory of Open Access Journals (Sweden)

    Cengiz Kocak

    2016-01-01

    Full Text Available Intestinal ischemia-reperfusion (I/R causes severe destruction in remote organs. Lung damage is a frequently seen complication after intestinal I/R. Ukrain (NSC 631570 is a synthetic thiophosphate derivative of alkaloids from the extract of the celandine (Chelidonium majus L. plant. We investigated the effect of Ukrain in animals with lung injury induced by intestinal I/R. Adult male Spraque-Dawley rats were randomly divided into four groups: control, Ukrain, I/R, I/R with Ukrain. Before intestinal I/R was induced, Ukrain was administered intraperitoneally at a dose of 7.0 mg/body weight. After 1 h ischemia and 2 h reperfusion period, lung tissues were excised. Tissue levels of total oxidative status (TOS, total antioxidant status (TAS were measured and oxidative stress indices (OSI were calculated. Lung tissues were also examined histopathologically. TOS and OSI levels markedly increased and TAS levels decreased in the I/R group compared to the control group (P < 0.05. TOS and OSI levels markedly decreased and TAS levels increased in the I/R with Ukrain group compared with the group subjected to IR only (P < 0.05. Severe hemorrhage, alveolar septal thickening, and leukocyte infiltration were observed  in the I/R group. In the I/R with Ukrain group, morphologic changes occurring as a result of lung damage attenuated and histopathological scores reduced compared to the I/R group (P < 0.05. Our results suggest that Ukrain pretreatment could reduce lung injury induced by intestinal I/R induced via anti-inflammatory and antioxidant effects. 

  18. 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.

  19. 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.

    2014-01-01

    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. PMID:24958709

  20. Systemic complement activation, lung injury, and products of lipid peroxidation.

    OpenAIRE

    Ward, P. A.; Till, G O; Hatherill, J. R.; Annesley, T M; Kunkel, R G

    1985-01-01

    Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxid...

  1. 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.

  2. RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury.

    Science.gov (United States)

    Zhang, Zhuo; Zhou, Jie; Liao, Changli; Li, Xiaobing; Liu, Minghua; Song, Daqiang; Jiang, Xian

    2017-04-01

    Lidocaine (Lido) is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of cecal ligation and puncture (CLP)-induced acute lung injury (ALI). The receptor for advanced glycation end product (RAGE) exerts pro-inflammatory effects by enhancing pro-inflammatory cytokine production. However, the precise mechanism by which Lido confers protection against ALI is not clear. ALI was induced in RAGE WT and RAGE knockout (KO) rats using cecal ligation and puncture (CLP) operations for 24 h. The results showed that Lido significantly inhibited CLP-induced lung inflammation and histopathological lung injury. Furthermore, Lido significantly reduced CLP-induced upregulation of HMGB1 and RAGE expression and activation of the NF-κB and MAPK signaling pathways. With the use of RAGE KO rats, we demonstrate here that RAGE deficiency attenuates the protective effect of Lido against CLP-induced lung inflammatory cell infiltration and histopathological lung injury. These results suggest that RAGE deficiency attenuates the protective effect of Lido against CLP-induced ALI by attenuating the pro-inflammatory cytokines production.

  3. 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.

  4. 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.  

  5. [The study of using cordyceps-astragalus-salvia miltiorrhiza to treat acute lung injury induced by paraquat poisoning in rats].

    Science.gov (United States)

    Li, Q L; Liu, J L; Wang, J R; Jian, X D; Kan, B T; Zhang, Z C

    2017-04-20

    Objective: To study the therapy of cordyceps-astragalus-salvia miltiorrhiza in treating acute lung injury and pulmonary interstitial fibrosis induced by paraquat poisoning. Methods: All 120 adult Wister male rats were randomly assigned to three groups, the paraquat poisoning group (rats were intragastric administration paraquat 50 mg/kg body weight once at the beginning) , the cordyceps-astragalus-salvia miltiorrhiza therapy group (rats were given cordyceps-astragalus-salvia miltiorrhiza 90 mg/kg body weight intragastric administration half an hour after paraquat was given, then the same dose was given once a day) ; control group (rats were intragastric administration with physiological saline) . At 7th, 14th, 21st, and 28th day rats were sacrificed postanesthetic respectively after paraquat exposure, sample of lung tissue, bronchoalveolar lavage (BAL) , and venous blood were collected. GSH, SOD, TNF-α, TGF-β1, and HYP in plasma, bronchoalveolar lavage (BAL) , and the lung homogenates were determined. Optical microscope was performed to examine pathological changes in lung. Results: Each experimental time point paraquat group and the treatment group rats serum SOD content significantly lower than the control group (P<0.05) . Each experimental time point the treatment group rats serum SOD levels increased significantly than that of paraquat group (P<0.05) . Each experimental time point paraquat group rats serum GSH content significantly lower than that of the control group (P<0.05) . Treatment group rats 7 days time GSH content significantly lower than that of the control group (P<0.05) . Treatment group 21 days, 28 days GSH content was increased significantly than that of the paraquat group (P<0.05) . Each experimental time point paraquat group rats alveolar lavage SOD content was significantly lower than that of the control group (P<0.05) . Treatment group 7 days, 14 days time SOD content was significantly lower than that of the control group (P<0

  6. Effect of captopril on serum TNF-α level in acute lung injury rats induced by HCL

    Institute of Scientific and Technical Information of China (English)

    Hong-Mei Liu; Yu-Na Guo

    2014-01-01

    Objective:To observe the effect of captopril on the tumor necrosis factor-α (TNF-α) level and arterial blood gases in acute lung injury (ALI) induced by HCL in rats, and to analyze its protective mechanism. Methods:Fifty Wistar rats were selected and randomly divided into three groups, with 20 rats in GroupⅠandⅡ, respectively and 10 animals in GroupⅢ. ALI model was constructed by intratracheal injection of diluted hydrochloric acid (pH=1.25, 1.2 mL/kg). Group I rats received not any treatment after construction of ALI model. GroupⅡrats were treated with captopril (5 mg/kg, i.p.) 5 min after induction of ALI. GroupⅢserved as normal control without any treatment. Ninety minutes after construction of ALI model, all the rats were sacrificed. Blood was withdrawn for detection of TNF-αlevel and arterial blood gases index. And lung tissue slices of the three groups were prepared for observation of pathologic histology changes. Results:TNF-αlevel in serum of GroupⅠand Ⅱrats was significantly higher than that in GroupⅢ(P<0.05), while TNF-αlevel in serum of GroupⅡwas significantly lower in Group I (P<0.05). PaCO2 level was significantly higher (P<0.05), while PaO2 was significantly lower (P<0.05) in Group I andⅡrats than those in GroupⅢ. PaCO2 was significantly lower (P<0.05) and PaO2 was significantly higher (P<0.05) in GroupⅡthan those in Group I. Histological observation showed diffuse congestion and severe edema of lung tissue, obvious thickening and structure damage of alveolar walls and a large amount of neutrophil infiltration in Group I rats. GroupⅡrats showed mild edema of lung tissue;only a small portion of alveolar walls showed thickening and only a few of neutrophil infiltration could be observed. The degree of injury was remarkably slighter than that of Group I rats. GroupⅢrats showed clear lung tissue structure and normal morphology;alveolar walls were uniform and the margin was smooth and few neutrophil could be observed

  7. Acute inflammation decreases the expression of connexin 40 in mouse lung.

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    Rignault, Stéphanie; Haefliger, Jacques-Antoine; Waeber, Bernard; Liaudet, Lucas; Feihl, François

    2007-07-01

    Transmigration of neutrophil polymorphonuclear leukocytes through the microvascular endothelium is a cardinal event of acute inflammation. In vitro, this process can be restricted by gap junctional intercellular communication, but whether it also occurs in vivo is unknown. Connexin 40 (Cx40) is a gap junctional protein abundantly present in the lung, notably in vascular endothelium. We hypothesized that acute lung inflammation would be aggravated in knockout mice genetically deficient in Cx40. This hypothesis was tested in two different models: 1) intranasal instillation of LPS at either supramaximal (50 microg/mouse) or inframaximal dose (0.01 microg/mouse) and 2) pulmonary inflammation as a distant consequence of an abdominal infection caused by cecal ligation and perforation. Pulmonary transmigration of neutrophils was assessed by counting these cells in bronchoalveolar lavage fluid (LPS model) or with the myeloperoxidase assay in homogenates of blood-free tissue (cecal ligation and perforation model). Pulmonary content in Cx40 and Cx43 was evaluated with immunoblots. In wild-type mice, there was a time-dependent decrease of Cx40 expression in both models. The time points for studies with the knockout mice were chosen in such a manner that inflammation was clearly present and Cx40 still largely expressed in wild-type animals. In either model, the development of lung inflammation did not differ between wild-type and Cx40-deficient mice. In conclusion, the pulmonary expression of the Cx40 protein is progressively and markedly decreased in two different murine models of acute lung inflammation, but there is no causal relationship between this process and the pulmonary transmigration of neutrophils.

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

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    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.

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

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    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.

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

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    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.

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

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    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.

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

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    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.

  13. 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.

  14. Circulating miRNAs as Biomarkers of Acute Muscle Damage in Rats.

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    Siracusa, Julien; Koulmann, Nathalie; Bourdon, Stéphanie; Goriot, Marie-Emmanuelle; Banzet, Sébastien

    2016-05-01

    Skeletal muscle damage is an often-occurring event. Diagnosis using the classic blood marker creatine kinase sometimes yields unsatisfactory results due to great interindividual variability. Therefore, the identification of reliable biomarkers is important. Our aim was to detect and characterize circulating miRNAs in plasma in response to acute notexin-induced muscle damage in rats. Real-time quantitative RT-PCR profiling led to the identification of miRNAs that were highly increased in plasma in response to notexin injection into several muscles, namely miR-1-3p, -133a-3p, -133b-3p, -206-3p, -208b-3p, and -499-5p, as well as miR-378a-3p and miR-434-3p. Peak values of miRNAs appeared 12 hours after injury, and were contained both in the vesicular and nonvesicular fractions of plasma. Receiver operating characteristic curve analysis showed that circulating miRNAs could accurately discriminate between damaged and nondamaged tissues. Furthermore, we tested the robustness of expression profiles in slow- and fast-type fibers. Upon inducing damage in slow- or fast-type muscle, we found that the damaged-muscle phenotype had a very limited impact on the miRNA response. Similarly, the circulating miRNAs selected were not affected by hemolysis or platelets, two pre-analytical factors known to affect plasma miRNA profiles. Taken together, our results show that circulating muscle-specific miRNAs, miR-378a-3p and miR-434-3p, are robust and promising biomarkers of acute muscle damage in rats.

  15. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

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    la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

    2013-01-01

    OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

  16. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

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    Francisco Javier Guzmán-de la Garza

    2013-07-01

    Full Text Available OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student’s t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion.

  17. Bisdemethoxycurcumin induces DNA damage and inhibits DNA repair associated protein expressions in NCI-H460 human lung cancer cells.

    Science.gov (United States)

    Yu, Chien-Chih; Yang, Su-Tso; Huang, Wen-Wen; Peng, Shu-Fen; Huang, An-Cheng; Tang, Nou-Ying; Liu, Hsin-Chung; Yang, Mei-Due; Lai, Kuang-Chi; Chung, Jing-Gung

    2016-12-01

    Nonsmall cell lung carcinoma (NSCLC) is a devastating primary lung tumor resistant to conventional therapies. Bisdemethoxycurcumin (BDMC) is one of curcumin derivate from Turmeric and has been shown to induce NSCLC cell death. Although there is one report to show BDMC induced DNA double strand breaks, however, no available information to show BDMC induced DNA damage action with inhibited DNA repair protein in lung cancer cells in detail. In this study, we tested BDMC-induced DNA damage and condensation in NCI-H460 cells by using Comet assay and DAPI staining examinations, respectively and we found BDMC induced DNA damage and condension. Western blotting was used to examine the effects of BDMC on protein expression associated with DNA damage and repair and results indicated that BDMC suppressed the protein levels associated with DNA damage and repair, such as 14-3-3σ (an important checkpoint keeper of DDR), O6-methylguanine-DNA methyltransferase, DNA repair proteins breast cancer 1, early onset, mediator of DNA damage checkpoint 1 but activate phosphorylated p53 and p-H2A.X (phospho Ser140) in NCI-H460 cells. Confocal laser systems microscopy was used for examining the protein translocation and results show that BDMC increased the translocation of p-p53 and p-H2A.X (phospho Ser140) from cytosol to nuclei in NCI-H460 cells. In conclusion, BDMC induced DNA damage and condension and affect DNA repair proteins in NCI-H460 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1859-1868, 2016. © 2015 Wiley Periodicals, Inc.

  18. Post-irradiation dietary vitamin E does not affect the development of radiation-induced lung damage in rats.

    Science.gov (United States)

    Wiegman, Erwin M; van Gameren, Mieke M; Kampinga, Harm H; Szabó, Ben G; Coppes, Rob P

    2004-07-01

    The purpose of this study was to investigate whether application of post-irradiation vitamin E, an anti-oxidant, could prevent the development of radiation induced lung damage. Wistar rats were given vitamin E enriched or vitamin E deprived food starting from 4 weeks after 18Gy single dose irradiation of the right thorax. Neither breathing frequencies nor CT density measurements revealed differences between the groups. It is concluded that post-irradiation vitamin E does not influence radiation-induced fibrosis to the lung.

  19. Lung damage following bone marrow transplantation. II. The contribution of cyclophosphamide

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    Varekamp, A.E.; de Vries, A.J.; Zurcher, C.; Hagenbeek, A.

    1987-10-01

    The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose rate (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy.

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

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    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

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

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    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

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

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    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.

  3. 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.

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

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    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. EFFECT OF HELICOBACTER PYLORI INFECTION ON ACUTE STRESS-RELATED GASTRIC MUCOSAL DAMAGE OF SERIOUSLY ILL PATIENTS

    Institute of Scientific and Technical Information of China (English)

    赵超; 肖文; 叶光福; 周建平; 周其璋

    2002-01-01

    Emergency endoscopy studies have shown that the most of seriously ill patients develop acute stress-related mucosal damage and ulceration within 24 hours of admission, which manifest the upper gastrointestinal tract

  6. Toxin-induced necroptosis is a major mechanism of Staphylococcus aureus lung damage.

    Science.gov (United States)

    Kitur, Kipyegon; Parker, Dane; Nieto, Pamela; Ahn, Danielle S; Cohen, Taylor S; Chung, Samuel; Wachtel, Sarah; Bueno, Susan; Prince, Alice

    2015-04-01

    Staphylococcus aureus USA300 strains cause a highly inflammatory necrotizing pneumonia. The virulence of this strain has been attributed to its expression of multiple toxins that have diverse targets including ADAM10, NLRP3 and CD11b. We demonstrate that induction of necroptosis through RIP1/RIP3/MLKL signaling is a major consequence of S. aureus toxin production. Cytotoxicity could be prevented by inhibiting either RIP1 or MLKL signaling and S. aureus mutants lacking agr, hla or Hla pore formation, lukAB or psms were deficient in inducing cell death in human and murine immune cells. Toxin-associated pore formation was essential, as cell death was blocked by exogenous K+ or dextran. MLKL inhibition also blocked caspase-1 and IL-1β production, suggesting a link to the inflammasome. Rip3(-/-) mice exhibited significantly improved staphylococcal clearance and retained an alveolar macrophage population with CD200R and CD206 markers in the setting of acute infection, suggesting increased susceptibility of these leukocytes to necroptosis. The importance of this anti-inflammatory signaling was indicated by the correlation between improved outcome and significantly decreased expression of KC, IL-6, TNF, IL-1α and IL-1β in infected mice. These findings indicate that toxin-induced necroptosis is a major cause of lung pathology in S. aureus pneumonia and suggest the possibility of targeting components of this signaling pathway as a therapeutic strategy.

  7. Toxin-induced necroptosis is a major mechanism of Staphylococcus aureus lung damage.

    Directory of Open Access Journals (Sweden)

    Kipyegon Kitur

    2015-04-01

    Full Text Available Staphylococcus aureus USA300 strains cause a highly inflammatory necrotizing pneumonia. The virulence of this strain has been attributed to its expression of multiple toxins that have diverse targets including ADAM10, NLRP3 and CD11b. We demonstrate that induction of necroptosis through RIP1/RIP3/MLKL signaling is a major consequence of S. aureus toxin production. Cytotoxicity could be prevented by inhibiting either RIP1 or MLKL signaling and S. aureus mutants lacking agr, hla or Hla pore formation, lukAB or psms were deficient in inducing cell death in human and murine immune cells. Toxin-associated pore formation was essential, as cell death was blocked by exogenous K+ or dextran. MLKL inhibition also blocked caspase-1 and IL-1β production, suggesting a link to the inflammasome. Rip3(-/- mice exhibited significantly improved staphylococcal clearance and retained an alveolar macrophage population with CD200R and CD206 markers in the setting of acute infection, suggesting increased susceptibility of these leukocytes to necroptosis. The importance of this anti-inflammatory signaling was indicated by the correlation between improved outcome and significantly decreased expression of KC, IL-6, TNF, IL-1α and IL-1β in infected mice. These findings indicate that toxin-induced necroptosis is a major cause of lung pathology in S. aureus pneumonia and suggest the possibility of targeting components of this signaling pathway as a therapeutic strategy.

  8. Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

    Energy Technology Data Exchange (ETDEWEB)

    Magnani, Natalia D.; Marchini, Timoteo; Vanasco, Virginia [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Tasat, Deborah R. [CESyMA, Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires (Argentina); Alvarez, Silvia [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Evelson, Pablo, E-mail: pevelson@ffyb.uba.ar [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina)

    2013-07-01

    Reactive O{sub 2} species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O{sub 2} species involved in lung O{sub 2} metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O{sub 2} consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H{sub 2}O{sub 2} and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O{sub 2} consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O{sub 2} consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H{sub 2}O{sub 2} production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O{sub 2} consumption may account for an augmented Nox activity, causing an increased O{sub 2}{sup ·−} production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O{sub 2} species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O{sub 2} consumption. • Exposure to ROFA

  9. 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.

  10. 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.

  11. 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.

  12. Inflammation in lung after acute myocardial infarction is induced by dendritic cell-mediated immune response.

    Science.gov (United States)

    Hu, L J; Ren, W Y; Shen, Q J; Ji, H Y; Zhu, L

    2017-01-01

    The present study was performed to describe the changes of lung tissues in mice with acute myocardial infarction (AMI) and also explain the cell mechanism involved in inflammation in lung. AMI was established by left coronary ligation in mice. Then mice were divided into three groups: control group, MW1 group (sampling after surgery for one week) and MW2 group (sampling after surgery for two weeks). Afterwards, measurement of lung weight and lung histology, cell sorting in bronchoalveolar lavage (BAL) fluid and detection of several adhesive molecules, inflammatory molecules as well as enzyme associated with inflammation were performed. Moreover, dendritic cells (DCs) were isolated from bone marrow of C57B/L6 mice. After incubating with necrotic myocardium, the expression of antigen presenting molecules, co-stimulatory molecules and inflammatory molecules were detected by flow cytometry or immunohistochemistry in DCs. We also detected T-cell proliferation after incubating with necrotic myocardium-treated DCs. AMI induced pathological changes of lung tissue and increased inflammatory cell amount in BAL fluid. AMI also increased the expression of several inflammatory factors, adhesive molecules and enzymes associated with inflammation. CD11c and TLR9, which are DC surface markers, showed a significantly increased expression in mice with AMI. Additionally, necrotic myocardium significantly increased the expression of co-stimulatory factors including CD83 and CD80, inflammatory cytokines including TNF-α, IFN-γ and NF-κB in DCs. Furthermore, DCs treated with necrotic myocardium also significantly promoted T-cell proliferation. AMI induced inflammation in lung and these pathological changes were mediated by DC-associated immune response.

  13. 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.

  14. DNA damage response (DDR) pathway engagement in cisplatin radiosensitization of non-small cell lung cancer.

    Science.gov (United States)

    Sears, Catherine R; Cooney, Sean A; Chin-Sinex, Helen; Mendonca, Marc S; Turchi, John J

    2016-04-01

    Non-small cell lung cancers (NSCLC) are commonly treated with a platinum-based chemotherapy such as cisplatin (CDDP) in combination with ionizing radiation (IR). Although clinical trials have demonstrated that the combination of CDDP and IR appear to be synergistic in terms of therapeutic efficacy, the mechanism of synergism remains largely uncharacterized. We investigated the role of the DNA damage response (DDR) in CDDP radiosensitization using two NSCLC cell lines. Using clonogenic survival assays, we determined that the cooperative cytotoxicity of CDDP and IR treatment is sequence dependent, requiring administration of CDDP prior to IR (CDDP-IR). We identified and interrogated the unique time and agent-dependent activation of the DDR in NSCLC cells treated with cisplatin-IR combination therapy. Compared to treatment with CDDP or IR alone, CDDP-IR combination treatment led to persistence of γH2Ax foci, a marker of DNA double-strand breaks (DSB), for up to 24h after treatment. Interestingly, pharmacologic inhibition of DDR sensor kinases revealed the persistence of γ-H2Ax foci in CDDP-IR treated cells is independent of kinase activation. Taken together, our data suggest that delayed repair of DSBs in NSCLC cells treated with CDDP-IR contributes to CDDP radiosensitization and that alterations of the DDR pathways by inhibition of specific DDR kinases can augment CDDP-IR cytotoxicity by a complementary mechanism.

  15. DNA damage response signaling in lung adenocarcinoma A549 cells following gamma and carbon beam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Somnath [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Narang, Himanshi, E-mail: himinarang@gmail.com [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Sarma, Asitikantha [Radiation Biology Laboratory, Inter University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110 067 (India); Krishna, Malini [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2011-11-01

    Carbon beams (5.16 MeV/u, LET = 290 keV/{mu}m) are high linear energy transfer (LET) radiation characterized by higher relative biological effectiveness than low LET radiation. The aim of the current study was to determine the signaling differences between {gamma}-rays and carbon ion-irradiation. A549 cells were irradiated with 1 Gy carbon or {gamma}-rays. Carbon beam was found to be three times more cytotoxic than {gamma}-rays despite the fact that the numbers of {gamma}-H2AX foci were same. Percentage of cells showing ATM/ATR foci were more with {gamma}-rays however number of foci per cell were more in case of carbon irradiation. Large BRCA1 foci were found in all carbon irradiated cells unlike {gamma}-rays irradiated cells and prosurvival ERK pathway was activated after {gamma}-rays irradiation but not carbon. The noteworthy finding of this study is the early phase apoptosis induction by carbon ions. In the present study in A549 lung adenocarcinoma, authors conclude that despite activation of same repair molecules such as ATM and BRCA1, differences in low and high LET damage responses might be due to their distinct macromolecular complexes rather than their individual activation and the activation of cytoplasmic pathways such as ERK, whether it applies to all the cell lines need to be further explored.

  16. Effects of methylene blue in acute lung injury induced by oleic acid in rats

    Science.gov (United States)

    Cassiano Silveira, Ana Paula; Vento, Daniella Alves; Albuquerque, Agnes Afrodite Sumarelli; Celotto, Andrea Carla; Tefé-Silva, Cristiane; Ramos, Simone Gusmão; Rubens de Nadai, Tales; Rodrigues, Alfredo José; Poli-Neto, Omero Benedicto

    2016-01-01

    Background In acute lung injury (ALI), rupture of the alveolar-capillary barrier determines the protein-rich fluid influx into alveolar spaces. Previous studies have reported that methylene blue (MB) attenuates such injuries. This investigation was carried out to study the MB effects in pulmonary capillary permeability. Methods Wistar rats were divided into five groups: (I) Sham: saline bolus; (II) MB, MB infusion for 2 h; (III) oleic acid (OA), OA bolus; (IV) MB/OA, MB infusion for 2 h, and at 5 min after from the beginning, concurrently with an OA bolus; and (V) OA/MB, OA bolus, and after 2 h, MB infusion for 2 h. After 4 h, blood, bronchoalveolar lavage (BAL), and lung tissue were collected from all groups for analysis of plasma and tissue nitric oxide, calculation of the wet weight to dry weight ratio (WW/DW), and histological examination of lung tissue. Statistical analysis was performed using nonparametric test. Results Although favourable trends have been observed for permeability improvement parameters (WW/WD and protein), the results were not statistically significant. However, histological analysis of lung tissue showed reduced lesion areas in both pre- and post-treatment groups. Conclusions The data collected using this experimental model was favourable only through macroscopic and histological analysis. These observations are valid for both MB infusions before or after induction of ALI. PMID:26855944

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. Effects ofSalmonella infection on hepatic damage following acute liver injury in rats

    Institute of Scientific and Technical Information of China (English)

    Yong-Tao Li; Cheng-Bo Yu; Dong Yan; Jian-Rong Huang; Lan-Juan Li

    2016-01-01

    BACKGROUND: Acute liver injury is a common clinical disor-der associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The pur-pose of this study was to address this unanswered question using a rat model. METHODS: Oral supplementation withSalmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the con-centrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury. RESULTS: The levels of liver damage and endotoxin were sig-niifcantly increased in theSalmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury (P CONCLUSIONS: OralS. enteritidis administration exacer-bates acute liver injury, especially when injury was severe. Major factors of the exacerbation include inlfammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

  7. Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Wei-Ming Lin

    2014-01-01

    Full Text Available The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI. However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.

  8. 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.

  9. 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

  10. Protective effect of Eleteria cardamomum (L.) Maton against Pan masala induced damage in lung of male Swiss mice

    Institute of Scientific and Technical Information of China (English)

    Sweety Kumari; Abhijit Dutta

    2013-01-01

    Objective: To study the potential ameliorating properties of cardamom Elettaria cardamomum (E. cardamomum) L. Maton against pan masala induced damage in lung of male Swiss mice. Methods: The experimental animals were divided into 3 groups (control, pan masala treated group and pan masala with cardamom treated group) to evaluate pan masala toxicity. The observations were substantiated with profound changes in the lung tissue as revealed in the histologic and transmission electron microscopic examinations. Results: Lung of pan masala treated group showed adenocarcinoma, edema, and inflammation with increased activity of acid phosphatase, alkaline phosphatase, and lactate dehydrogenase. The deleterious effects were seen to be less in cardamom treated group and the enzymatic activity also decreased significantly (P<0.05) in the ameliorating group. Conclusions: Thus, the present experiment exciting results are observed when cardamom is supplemented with pan masala, or when given alone.

  11. Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits.

    Science.gov (United States)

    Diao, Mengyuan; Zhang, Sheng; Wu, Lifeng; Huan, Le; Huang, Fenglou; Cui, Yunliang; Lin, Zhaofen

    2016-12-01

    Seawater instillation-induced acute lung injury involves oxidative stress and apoptosis. Although hydrogen gas inhalation is reportedly protective in multiple types of lung injury, the effect of hydrogen gas inhalation on seawater instillation-induced acute lung injury remains unknown. This study investigated the effect of hydrogen gas on seawater instillation-induced acute lung injury and explored the mechanisms involved. Rabbits were randomly assigned to control, hydrogen (2 % hydrogen gas inhalation), seawater (3 mL/kg seawater instillation), and seawater + hydrogen (3 mL/kg seawater instillation + 2 % hydrogen gas inhalation) groups. Arterial partial oxygen pressure and lung wet/dry weight ratio were detected. Protein content in bronchoalveolar lavage fluid (BALF) and serum as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were determined. Hematoxylin-eosin staining was used to monitor changes in lung specimens, and malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were assayed. In addition, NF-E2-related factor (Nrf) 2 and heme oxygenase (HO)-1 mRNA and protein expression were measured, and apoptosis was assessed by measuring caspase-3 expression and using terminal deoxy-nucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Hydrogen gas inhalation markedly improved lung endothelial permeability and decreased both MDA content and MPO activity in lung tissue; these changes were associated with decreases in TNF-α, IL-1β, and IL-6 in BALF. Hydrogen gas also alleviated histopathological changes and cell apoptosis. Moreover, Nrf2 and HO-1 expressions were significantly activated and caspase-3 expression was inhibited. These results demonstrate that hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury in rabbits and that the protective effects observed may be related to the activation of the Nrf2 pathway.

  12. Oxidative damage and histopathological changes in lung of rat chronically exposed to nicotine alone or associated to ethanol.

    Science.gov (United States)

    Dhouib, H; Jallouli, M; Draief, M; Bouraoui, S; El-Fazâa, S

    2015-12-01

    Smoking is the most important preventable risk factor of chronic obstructive pulmonary disease and lung cancer. This study was designed to investigate oxidative damage and histopathological changes in lung tissue of rats chronically exposed to nicotine alone or supplemented with ethanol. Twenty-four male Wistar rats divided into three groups were used for the study. The nicotine group received nicotine (2.5mg/kg/day); the nicotine-ethanol group was given simultaneously same dose of nicotine plus ethanol (0.2g/kg/day), while the control group was administered only normal saline (1 ml/kg/day). The treatment was administered by subcutaneous injection once daily for a period of 18 weeks. Chronic nicotine administration alone or combined to ethanol caused a significant increase in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and catalase (CAT) activity in lung tissue compared to control rats suggesting an oxidative damage. However, these increases were mostly prominent in nicotine group. The histopathological examination of lung tissue of rats in both treated groups revealed many alterations in the pulmonary structures such as emphysema change (disappearance of the alveolar septa, increased irregularity and size of air sacs) and marked lymphocytic infiltration in perivascular and interstitial areas. However, the changes characterized in the nicotine group (pulmonary congestion, hemorrhage into alveoli and interstitial areas, edema) were more drastic than those observed in the nicotine-ethanol group, and they can be attributed to a significant degree of capillary endothelial permeability and microvascular leak. Conversely, the ethanol supplementation caused an appearance of fatty change and fibrosis in pulmonary tissue essentially due to a metabolism of ethanol. Finally, the lung damage illustrated in nicotine group was more severe than that observed in the nicotine-ethanol group. We conclude that the combined administration of nicotine and ethanol

  13. Targeting the Renin–Angiotensin System Combined With an Antioxidant Is Highly Effective in Mitigating Radiation-Induced Lung Damage

    Energy Technology Data Exchange (ETDEWEB)

    Mahmood, Javed [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Jelveh, Salomeh [Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Zaidi, Asif [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Doctrow, Susan R. [Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts (United States); Medhora, Meetha [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Hill, Richard P., E-mail: hill@uhnres.utoronto.ca [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2014-07-15

    Purpose: To investigate the outcome of suppression of the renin angiotensin system using captopril combined with an antioxidant (Eukarion [EUK]-207) for mitigation of radiation-induced lung damage in rats. Methods and Materials: The thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine transforming growth factor-β1 and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid peroxidation was measured by a T-BARS assay. Results: The increase in breathing rate in the irradiated rats was significantly reduced by the drug treatments. The drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy-2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages and the cytokine transforming growth factor-β1 at 32 weeks. Almost complete mitigation of these radiation effects was observed by combining captopril and EUK-207. Conclusion: Captopril and EUK-207 can provide mitigation of radiation-induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks PI. Overall the combination of captopril and EUK-207 was more effective than the individual drugs used alone.

  14. 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.

  15. 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.

  16. Lysine acetylsalicylate ameliorates lung injury in rats acutely exposed to paraquat

    Institute of Scientific and Technical Information of China (English)

    HUANG Wei-dong; WANG Jie-zan; LU Yuan-qiang; DI Ya-min; JIANG Jiu-kun; ZHANG Qin

    2011-01-01

    Background Paraquat (PQ), an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ mainly accumulates in the lung, and the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. The aim of this study was to evaluate whether lysine acetylsalicylate (LAS) could protect the lung from the damage of PQ poisoning and to study the mechanisms of protection.Methods A model of PQ poisoning was established in 75 Sprague-Dawley rats by intragastric administration of 50 mg/kg PQ, followed by treatment with 200 mg/kg of LAS. The rats were randomly divided into sham, PQ, and PQ+LAS groups, with 25 in each group. We assessed and compared the malonaldehyde (MDA) content, superoxide dismutase activity (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) in serum and lung and the hydroxyproline (HYP)content, pathological changes, apoptosis and expression of Bcl-2/Bax protein in lung of rats on days 1, 3, 7, 14 and 21after PQ poisoning and LAS treatment.Results Compared to the PQ group rats, early treatment with LAS reduced the MDA and HYP contents, and increased the SOD, GSH-Px, and CAT activities in the serum and lung on days 1, 3, 7, 14, and 21 after PQ poisoning (all P<0.05).After early LAS treatment, the apoptotic rate and Bax expression of lung decreased, the Bcl-2 expression increased, and the Bcl-2/Bax ratio increased, compared to the PQ group rats. Furthermore, the pathological results of lungs revealed that after LAS treatment, early manifestations of PQ poisoning, such as hemorrhage, edema and inflammatory-cell infiltration, were improved to some degree, and collagen fibers in the pulmonary interstitium were also obviously reduced.Conclusion In this rat model of PQ poisoning, LAS effectively ameliorated the lung

  17. Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

    DEFF Research Database (Denmark)

    Sørli, Jorid Birkelund; Huang, Yishi; Da Silva, Emilie

    2017-01-01

    numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21...... the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large...... impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if they inhibited LS function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e. the in vitro method predicted...

  18. 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.

  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. 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

  1. Metabolic fingerprinting to understand therapeutic effects and mechanisms of silybin on acute liver damage in rat

    Directory of Open Access Journals (Sweden)

    Qun Liang

    2015-01-01

    Full Text Available Background: Metabolic fingerprinting is a rapid and noninvasive analysis, representing a powerful approach for the characterization of phenotypes and the distinction of specific metabolic states due to environmental alterations. It has become a valuable analytical approach for the characterization of phenotypes and is the rapidly evolving field of the comprehensive measurement of ideally all endogenous metabolites in bio-samples. Silybin has displayed bright prospects in the prevention and therapy of liver injury, and we had conducted a preliminary exploration on the molecular mechanism of the hepatoprotective effects of silybin. Because the knowledge on the metabolic responses of an acute liver damage rat to the silybin is still scarce, metabolic fi ngerprinting can provide relevant information on the intrinsic metabolic adjustments. Materials and Methods: Here, the physiological and metabolic changes in the acute liver damage rat were investigated by performing a metabolic analysis. The phenotypic response was assessed by liquid chromatography/mass spectrometry (LC/MS combined with pattern recognition approaches such as principal components analysis and partial least squares projection to supervised latent structures and discriminant analysis. Multivariate analysis of the data showed trends in scores plots that were related to the concentration of the silybin. Results: Results indicate 10 ions (7 upregulated and 3 downregulated as differentiating metabolites. Key observations include perturbations of metabolic pathways linked to glutathione metabolism, tryptophan metabolism, cysteine and methionine metabolism, etc., Overall, this investigation illustrates the power of the LC/MS combined with the pattern recognition methods that can engender new insights into silybin affecting on metabolism pathways of an acute liver damage rat. Conclusion: The present study demonstrates that the combination of metabolic fi ngerprinting with appropriate

  2. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    Science.gov (United States)

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.

  3. Torsade de pointes indicates early neurologic damage in acute ischemic stroke.

    Science.gov (United States)

    Huang, Li-Yen; Lin, Wei-Shiang; Lin, Wen-Yu; Cheng, Cheng-Chung; Cheng, Shu-Meng; Tsai, Tsung-Neng

    2013-12-01

    Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia that is related to QT prolongation. Although QT prolongation is commonly seen in acute stroke, TdP is rare. We report the case of a 78-year-old woman with ischemic stroke who presented with TdP as the initial manifestation of early neurologic deterioration. We hypothesized that an increase in intracranial pressure may result in neurohormonal activation, QT prolongation, and then myocardial damage, leading to TdP. We highlight that new onset of TdP in a patient with stroke may reflect neurologic deterioration, requiring further evaluation and specific intervention.

  4. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Nakadate, Yusuke [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kodera, Yasuo; Kitamura, Yuka [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Tachibana, Taro [Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Tamura, Tomohide [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Koizumi, Fumiaki, E-mail: fkoizumi@ncc.go.jp [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  5. 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

  6. 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.

  7. Ketamine attenuates sepsis-induced acute lung injury via regulation of HMGB1-RAGE pathways.

    Science.gov (United States)

    Li, Kehan; Yang, Jianxue; Han, Xuechang

    2016-05-01

    High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play important roles in the development of sepsis-induced acute lung injury (ALI). Ketamine is considered to confer protective effects on ALI during sepsis. In this study, we investigated the effects of ketamine on HMGB1-RAGE activation in a rat model of sepsis-induced ALI. ALI was induced in wild type (WT) and RAGE deficient (RAGE(-/-)) rats by cecal ligation and puncture (CLP) or HMGB1 to mimic sepsis-induced ALI. Rats were randomly divided to six groups: sham-operation+normal saline (NS, 10 mL/kg), sham-operation+ketamine (10 mg/kg), CLP/HMGB1+NS (10 mL/kg), CLP/HMGB1+ketamine (5 mg/kg), CLP/HMGB1+ketamine (7.5 mg/kg), and CLP/HMGB1+ketamine (10 mg/kg) groups. NS and ketamine were administered at 3 and 12 h after CLP/HMGB1 via intraperitoneal injection. Pathological changes of lung, inflammatory cell counts, expression of HMGB1 and RAGE, and concentrations of various inflammatory mediators in bronchoalveolar lavage fluids (BALF) and lung tissue were then assessed. Nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in the lung were also evaluated. CLP/HMGB1 increased the wet to dry weight ratio and myeloperoxidase activity in lung, the number of total cells, neutrophils, and macrophages in the BALF, and inflammatory mediators in the BALF and lung tissues. Moreover, expression of HMGB1 and RAGE in lung tissues was increased after CLP. Ketamine inhibited all the above effects. It also inhibited the activation of IκB-α, NF-κB p65, and MAPK. Ketamine protects rats against HMGB1-RAGE activation in a rat model of sepsis-induced ALI. These effects may partially result from reductions in NF-κB and MAPK. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  8. Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure.

    Science.gov (United States)

    Porubsky, Stefan; Federico, Giuseppina; Müthing, Johannes; Jennemann, Richard; Gretz, Norbert; Büttner, Stefan; Obermüller, Nicholas; Jung, Oliver; Hauser, Ingeborg A; Gröne, Elisabeth; Geiger, Helmut; Gröne, Hermann-Josef; Betz, Christoph

    2014-09-01

    The pathogenesis and therapy of Shigatoxin 2 (Stx2)-mediated kidney failure remain controversial. Our aim was to test whether, during an infection with Stx2-producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium and thereby possibly contributes to acute renal failure. Mice represent a suitable model because they, like humans, express the Stx2-receptor Gb3 in the tubular epithelium but, in contrast to humans, not in glomerular endothelia, and are thus free of glomerular thrombotic microangiopathy (TMA). In wild-type mice, Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance, which was most likely the cause of death. Tubule-specific depletion of Gb3 protected the mice from acute renal failure. In vitro, Stx2 induced secretion of proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus implicating a direct effect of Stx2 on the tubular epithelium. To correlate these results to human disease, kidney biopsies and outcome were analysed in patients with Stx2-associated kidney failure (n = 11, aged 22-44 years). The majority of kidney biopsies showed different stages of an ongoing TMA; however, no glomerular complement activation could be demonstrated. All biopsies, including those without TMA, showed severe acute tubular damage. Due to these findings, patients were treated with supportive therapy without complement-inhibiting antibodies (eculizumab) or immunoadsorption. Despite the severity of the initial disease [creatinine 6.34 (1.31-17.60) mg/dl, lactate dehydrogenase 1944 (753-2792) U/l, platelets 33 (19-124)/nl and haemoglobin 6.2 (5.2-7.8) g/dl; median (range)], all patients were discharged after 33 (range 19-43) days with no neurological symptoms and no dialysis requirement [creatinine 1.39 (range 0.84-2.86) mg/dl]. The creatinine decreased further to 0.90 (range 0.66-1.27) mg/dl after 24 months. Based on these data, one may surmise that acute tubular damage represents a separate

  9. Bioactive Components from Qingwen Baidu Decoction against LPS-Induced Acute Lung Injury in Rats

    Directory of Open Access Journals (Sweden)

    Qi Zhang

    2017-04-01

    Full Text Available Qingwen Baidu Decoction (QBD is an extraordinarily “cold” formula. It was traditionally used to cure epidemic hemorrhagic fever, intestinal typhoid fever, influenza, sepsis and so on. The purpose of this study was to discover relationships between the change of the constituents in different extracts of QBD and the pharmacological effect in a rat model of acute lung injury (ALI induced by lipopolysaccharide (LPS. The study aimed to discover the changes in constituents of different QBD extracts and the pharmacological effects on acute lung injury (ALI induced by LPS. The results demonstrated that high dose and middle dose of QBD had significantly potent anti-inflammatory effects and reduced pulmonary edema caused by ALI in rats (p < 0.05. To explore the underlying constituents of QBD, we assessed its influence of six different QBD extracts on ALI and analyzed the different constituents in the corresponding HPLC chromatograms by a Principal Component Analysis (PCA method. The results showed that the pharmacological effect of QBD was related to the polarity of its extracts, and the medium polarity extracts E2 and E5 in particular displayed much better protective effects against ALI than other groups. Moreover, HPLC-DAD-ESI-MSn and PCA analysis showed that verbascoside and angoroside C played a key role in reducing pulmonary edema. In addition, the current study revealed that ethyl gallate, pentagalloylglucose, galloyl paeoniflorin, mudanpioside C and harpagoside can treat ALI mainly by reducing the total cells and infiltration of activated polymorphonuclear leukocytes (PMNs.

  10. 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.

  11. 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.

  12. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

    OpenAIRE

    Chan, Michael C W; Kuok, Denise I. T.; Leung, Connie Y. H.; Hui, Kenrie P Y; Valkenburg, Sophie A.; Lau, Eric H. Y.; Nicholls, John M; Fang, Xiaohui; Guan, Yi; Lee, Jae W; Chan, Renee W. Y.; Webster, Robert G; Matthay, Michael A.; Peiris, J. S. Malik

    2016-01-01

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstr...

  13. 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...

  14. 腹腔镜-胆道手术后-急性肺损伤%Laparoscopic-After billiard surgery-Acute lung injury

    Institute of Scientific and Technical Information of China (English)

    谢健; 招伟贤; 王海燕

    2011-01-01

    A case of acute lung injury after laparoscopic biliary surgery was reported. The 56-year-old male patient underwent laparoscopic cholecystectomy and choledocholithotomy under general anesthesia. He showed severe hypoxemia after the operation, and was resuscitated after 3 days of non-invasive BiPAP respiratory support and anti-inflammatory treatment. According to the features of significant hypoxemia without notable respiratory distress manifestation, severe infiltration in the lung, and attenuated breath sounds without obvious wet or dry rales, the diagnosis of a low pressure interstitial pulmonary edema was suggested. The pathogenesis may be due to the pulmonary capillary endothelial damage and increased permeability, thus both of water and plasma protein leaked into the lung interstitial. It should be noticed that the amino acid oxidase in hemocoagnlase could also induce acute lung injury.%报道1例56岁男性患者,在全身麻醉下行腹腔镜胆囊切除及胆总管切开取石术,术毕发生急性肺损伤,出现严重低氧血症.后经面罩双水平正压通气(bilevel positive airway pressure,BiPAP)呼吸支持及抗炎治疗3 d康复.患者低氧血症明显但无明显呼吸窘迫、双肺弥漫性浸润明显而听诊除呼吸音较弱外无明显干湿啰音的特点,提示为低压性肺间质水肿,其原因可能由于肺毛细血管内皮受损、通透性增加,水和血浆蛋白漏出进入肺间质所致.应当关注蛇毒中氨基酸氧化酶诱发的急性肺损伤.

  15. 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.

  16. 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

  17. Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury.

    Science.gov (United States)

    Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L; Connelly, Rhykka; Nakano, Yoshimitsu; Traber, Lillian D; Schmalstieg, Frank C; Herndon, David N; Enkhbaatar, Perenlei

    2012-11-01

    Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Sheep were randomized to a sham-injured control group (n=6) or ALI/sepsis group (n=7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24 h. Additional sheep (n=16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates. The injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (P<0.01 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (P<0.05 each). This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  18. Colonic Metastasis From a Primary Adenocarcinoma of the Lung Presenting with Acute Abdominal Pain: A Case Report

    Directory of Open Access Journals (Sweden)

    Ming-Wei Weng

    2010-01-01

    Full Text Available Colonic metastasis from lung cancer is rare and generally asymptomatic. Here, we report a case with lung adenocarcinoma that presented with acute abdominal pain due to intestinal obstruction caused by the metastatic colon tumor. The patient underwent emergency colonoscopy and the pathologic report was adenocarcinoma, which was the same as that for a bronchoscopic biopsy from a large lung mass. Immunohistochemistry was positive for thyroid transcription factor-1 and cytokeratin 7, and negative for cytokeratin 20 and caudal-related homeobox transcription factor 2 on both lung biopsy and colon surgical specimens. Accordingly, we used immunohisto-chemistry for thyroid transcription factor-1, cytokeratin 7, cytokeratin 20 and caudal-related homeobox transcription factor-2 to diagnose primary adenocarcinoma of the lung with colonic metastasis.

  19. Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-09

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

  20. 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.

  1. DNA damage focus analysis in blood samples of minipigs reveals acute partial body irradiation.

    Directory of Open Access Journals (Sweden)

    Andreas Lamkowski

    Full Text Available Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs. The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI with 49 Gy (± 6% Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL of 49 Gy partial body irradiated minipigs were found to display 1-8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets

    Institute of Scientific and Technical Information of China (English)

    WU Rui-ping; LIANG Xiu-bin; GUO Hui; ZHOU Xiao-shuang; ZHAO Li; WANG Chen; LI Rong-shan

    2012-01-01

    Background Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI).However,LPD solution for treating acute kidney injury secondary to ALI has not been reported.The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.Methods Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups:the placebo group (n=6) pretreated with normal saline and the LPD group (n=6),pretreated with LPD solution.LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.Results All animals survived the experiments with mild histopathological injury to the kidney.There were no significant differences in mean arterial pressure (MAP),creatinin and renal damage scores between the two groups.Compared with the placebo group,the LPD group had better gas exchange parameters at most of the observation points ((347.0±12.6)mmHg vs.(284.3±11.3) mmHg at 6 hours after ALI,P<0.01).After 6 hours of treatment with OA,the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0±0.6) and (2.50±0.08) folds in placebo group; and (2.5±0.5) and (1.40±0.05) folds in LPD group),but the change of both parameters in the LPD group was significantly lower (P <0.01) than in the placebo group.And 6 hours after ALl the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg.ml-1.g-1 protein) was significantly lower (P <0.01) than that in placebo group ((67.2± 25.3) pg.ml-1.g-1 protein).Conclusion These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALl piglet model induced by OA injection.

  7. Mycobacterium terrae isolated from indoor air of a moisture-damaged building induces sustained biphasic inflammatory response in mouse lungs.

    Science.gov (United States)

    Jussila, Juha; Komulainen, Hannu; Huttunen, Kati; Roponen, Marjut; Iivanainen, Eila; Torkko, Pirjo; Kosma, Veli-Matti; Pelkonen, Jukka; Hirvonen, Maija-Riitta

    2002-11-01

    Occupants in moisture-damaged buildings suffer frequently from respiratory symptoms. This may be partly due to the presence of abnormal microbial growth or the altered microbial flora in the damaged buildings. However, the specific effects of the microbes on respiratory health and the way they provoke clinical manifestations are poorly understood. In the present study, we exposed mice via intratracheal instillation to a single dose of Mycobacterium terrae isolated from the indoor air of a moisture-damaged building (1 X 10(7), 5 X 10(7), or 1 X 10(8) microbes). Inflammation and toxicity in lungs were evaluated 2 hr later. The time course of the effects was assessed with the dose of 1 X 10(8) bacterial cells for up to 28 days. M. terrae caused a sustained biphasic inflammation in mouse lungs. The characteristic features for the first phase, which lasted from 6 hr to 3 days, were elevated proinflammatory cytokine [i.e., tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)] levels in the bronchoalveolar lavage fluid (BALF). TNF-alpha was produced in the lungs more intensively than was IL-6. Neutrophils were the most abundant cells in the airways during the first phase, although their numbers in BALF remained elevated up to 21 days. The characteristics of the second phase, which lasted from 7 to 28 days, were elevated TNF-alpha levels in BALF, expression of inducible nitric oxide synthase in BAL cells, and recruitment of mononuclear cells such as lymphocytes and macrophages into the airways. Moreover, total protein, albumin, and lactate dehydrogenase concentrations were elevated in both phases in BALF. The bacteria were detected in lungs up to 28 days. In summary, these observations indicate that M. terrae is capable of provoking a sustained, biphasic inflammation in mouse lungs and can cause a moderate degree of cytotoxicity. Thus, M. terrae can be considered a species with potential to adversely affect the health of the occupants of moisture-damaged

  8. Nigella sativa improves the carbon tetrachloride-induced lung damage in rats through repression of erk/akt pathway

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    Abdullah Aslan

    2015-08-01

    Full Text Available The objective of this study was to examine whether Nigella sativa plays a protective role against the damage in the lung by administering carbon tetra-chloride (CCl4 to rats. Male Wistar albino (n=28, 8 weeks old rats were divided into 4 groups: a negative control: Normal water consuming group to which no CCl4 and N. sativa was administered; b Positive control: Normal water consuming group to which no CCl4 was administered but N. sativa was administered; c CCl4 Group: Normal water consuming and group to which CCl4 was administered (1.5 mL/kg, ip; d N. sativa plus CCl4 group: CCl4 and N. sativa administered group (1.5 mL/kg, ip. Caspase-3, caspase -9, erk, akt protein syntheses were examined via Western blotting. Malondialdehyde determination in lung tissue was made using spectrophotometer. As a results, malondialdehyde amount was decreased in the CCl4 plus N. sativa group in comparison to CCl4 group whereas caspase-3, caspase-9 was increased and erk, akt had decreased. These results show that N. sativa protects the lung against oxidative damage.

  9. Impact of acute exposure to WTC dust on ciliated and goblet cells in lungs of rats.

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    Cohen, Mitchell D; Vaughan, Joshua M; Garrett, Brittany; Prophete, Colette; Horton, Lori; Sisco, Maureen; Ghio, Andrew; Zelikoff, Judith; Lung-chi, Chen

    2015-01-01

    Clinical studies and the World Trade Center (WTC) Health Registry have revealed increases in the incidence of chronic (non-cancer) lung disorders among first responders (FR) who were at Ground Zero during the initial 72 h after the collapse. Our previous analyses of rats exposed to building-derived WTC dusts using exposure scenarios/levels that mimicked FR mouth-breathing showed that a single WTC dust exposure led to changes in expression of genes whose products could be involved in the lung ailments, but few other significant pathologies. We concluded that rather than acting as direct inducers of many of the FR health effects, it was more likely inhaled WTC dusts instead may have impacted on toxicities induced by other rescue-related co-pollutants present in Ground Zero air. To allow for such effects to occur, we hypothesized that the alkaline WTC dusts induced damage to the normal ability of the lungs to clear inhaled particles. To validate this, rats were exposed on two consecutive days (2 h/d, by intratracheal inhalation) to WTC dust (collected 12-13 September 2001) and examined over a 1-yr period thereafter for changes in the presence of ciliated cells in the airways and hyperplastic goblet cells in the lungs. WTC dust levels in the lungs were assessed in parallel to verify that any changes in levels of these cells corresponded with decreases in host ability to clear the particles themselves. Image analyses of the rat lungs revealed a significant decrease in ciliated cells and increase in hyperplastic goblet cells due to the single series of WTC dust exposures. The study also showed there was only a nominal non-significant decrease (6-11%) in WTC dust burden over a 1-yr period after the final exposure. These results provide support for our current hypothesis that exposure to WTC dusts caused changes in airway morphology/cell composition; such changes could, in turn, have led to potential alterations in the clearance/toxicities of other pollutants inhaled

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

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    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.

  11. [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.

  12. 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.

  13. 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.

  14. The radioprotective effect and mechanism of captopril on radiation induced lung damage in rat

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    Song, Mi Hee; Lee, Kyung Ja; Koo, Hea Soo; Oh, Won Young [College of Medicine, Ewha Women Univ., Seoul (Korea, Republic of)

    2001-06-01

    It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We performed this study to investigate the radioprotective effect and mechanism of Captopril. The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains (TNF {alpha} and TGF {beta}1) at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radiation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominent in the combined Captopril and radiation group. At 2 weeks, the TNF {alpha} expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the TGF {beta}1 expression was significantly prominent at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p< 0.02). At 8 weeks, the expression of TNF {alpha} and TGF {beta} 1 of most sites, except TGF {beta}1 of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of TNF {alpha} and TGF {beta} 1 at 2 weeks and TGF {beta} 1 at

  15. TRAIL+ monocytes and monocyte-related cells cause lung damage and thereby increase susceptibility to influenza-Streptococcus pneumoniae coinfection.

    Science.gov (United States)

    Ellis, Gregory T; Davidson, Sophia; Crotta, Stefania; Branzk, Nora; Papayannopoulos, Venizelos; Wack, Andreas

    2015-09-01

    Streptococcus pneumoniae coinfection is a major cause of influenza-associated mortality; however, the mechanisms underlying pathogenesis or protection remain unclear. Using a clinically relevant mouse model, we identify immune-mediated damage early during coinfection as a new mechanism causing susceptibility. Coinfected CCR2(-/-) mice lacking monocytes and monocyte-derived cells control bacterial invasion better, show reduced epithelial damage and are overall more resistant than wild-type controls. In influenza-infected wild-type lungs, monocytes and monocyte-derived cells are the major cell populations expressing the apoptosis-inducing ligand TRAIL. Accordingly, anti-TRAIL treatment reduces bacterial load and protects against coinfection if administered during viral infection, but not following bacterial exposure. Post-influenza bacterial outgrowth induces a strong proinflammatory cytokine response and massive inflammatory cell infiltrate. Depletion of neutrophils or blockade of TNF-α facilitate bacterial outgrowth, leading to increased mortality, demonstrating that these factors aid bacterial control. We conclude that inflammatory monocytes recruited early, during the viral phase of coinfection, induce TRAIL-mediated lung damage, which facilitates bacterial invasion, while TNF-α and neutrophil responses help control subsequent bacterial outgrowth. We thus identify novel determinants of protection versus pathology in influenza-Streptococcus pneumoniae coinfection.

  16. Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan.

    Science.gov (United States)

    Shieh, Wun-Ju; Hsiao, Cheng-Hsiang; Paddock, Christopher D; Guarner, Jeannette; Goldsmith, Cynthia S; Tatti, Kathleen; Packard, Michelle; Mueller, Laurie; Wu, Mu-Zong; Rollin, Pierre; Su, Ih-Jen; Zaki, Sherif R

    2005-03-01

    This article describes the pathological studies of fatal severe acute respiratory syndrome (SARS) in a 73-year-old man during an outbreak of SARS in Taiwan, 2003. Eight days before onset of symptoms, he visited a municipal hospital that was later identified as the epicenter of a large outbreak of SARS. On admission to National Taiwan University Hospital in Taipei, the patient experienced chest tightness, progressive dyspnea, and low-grade fever. His condition rapidly deteriorated with increasing respiratory difficulty, and he died 7 days after admission. The most prominent histopathologic finding was diffuse alveolar damage of the lung. Immunohistochemical and in situ hybridization assays demonstrated evidence of SARS-associated coronavirus (SARS-CoV) infection in various respiratory epithelial cells, predominantly type II pneumocytes, and in alveolar macrophages in the lung. Electron microscopic examination also revealed coronavirus particles in the pneumocytes, and their identity was confirmed as SARS-CoV by immunogold labeling electron microscopy. This report is the first to describe the cellular localization of SARS-CoV in human lung tissue by using a combination of immunohistochemistry, double-stain immunohistochemistry, in situ hybridization, electron microscopy, and immunogold labeling electron microscopy. These techniques represent valuable laboratory diagnostic modalities and provide insights into the pathogenesis of this emerging infection.

  17. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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    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.

  18. 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.

  19. Acute lung injury following transcatheter hepatic arterial chemoembolization of doxorubicin-loaded LC beads in a patient with hepatocellular carcinoma

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    Ihsan Khan

    2012-01-01

    Full Text Available Transcatheter arterial chemoembolization (TACE currently is being used as an effective palliative therapy for unresectable cancers especially hepatocelluar carcinoma (HCC. Accidental lipiodol embolism to the lungs is a rare but potentially fatal complication of TACE. This procedure involves injection of drug-eluting microspheres (LC Bead loaded with doxorubicin, followed by embolization with embozene microspheres until stasis is evident, being used in advanced HCC. We report a patient with inoperable HCC with underlying Hepatitis C and liver cirrhosis, who developed acute lung injury following targeted chemoembolization of selective feeding hepatic artery with LC beads loaded with doxorubicin. Acute lung injury as a complication of unintended lung chemoembolization with doxorubicin has not been previously reported in the literature. Interventional radiologists screen patients for potential hepatic A-V shunt and take appropriate precautions to prevent unintended pulmonary embolization. These include appropriate selection of LC bead particle size especially in patients who are embolized with radiation pellets. This report highlights the need for a screening total body scintigraphy after injection of radionuclide Tc-99 MAA in the feeding hepatic artery to identify patients with hepatic A-V shunt. In such patients, appropriate size selection of LC bead particles is critical to prevent unintended pulmonary chemoembolization and acute lung injury. Other measures include careful patient selection, low dose of chemotherapy, and transient selective hepatic vein balloon occlusion.

  20. 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.

  1. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

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    Jianhui Chang

    Full Text Available One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE particles, such as oxygen (16O, carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE. Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n irradiation and examined the effects on peripheral blood (PB cells, and bone marrow (BM hematopoietic stem cells (HSCs and hematopoietic progenitor cells (HPCs at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS, enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the

  2. 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.

  3. Effect of Coenzyme Q10 on Acute Pulmonary Damage Following the Experimental Thoracic Trauma

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    Murat Koyuncu

    2016-04-01

    Full Text Available Aim: Pulmonary contusion negatively affects prognosis in the case of damages following a trauma. Objective of this experimental study performed in Turkey was to evaluate effects of coenzyme Q10 on primary and secondary damages of pulmonary contusion following experimental thoracic blunt trauma using biochemical and histopathological parameters. Material and Method: A total of 56 Wistar Albino female rats with a mean weight of 205±45 g were included in this study. Rats were randomly divided into seven groups with each group having eight rats. A trauma device which consisted of a fixed platform, and an aluminium tube was prepared. Rats were administered 2.45 J of chest impact energy in order to generate pulmonary contusion. Control and Study groups were named according to the sacrificed time. No process (trauma and/or medication was performed in the sham group, while only trauma was induced in the controls. On the other hand, after induced trauma, intraperitoneal Q10 (0. - 24. - 48. hours was administered to study group. Rats were sacrificed at the end of the after trauma 24, 48 and 72 hours, and their blood and lung tissue samples were analyzed. Results: No significant difference was found between sham and Study-72 groups in terms of high-sensitivity C-reactive protein. On the histopathological examination, no significant difference was found between study and control groups. While no significant difference was found between the sham and study groups, significant difference was observed between sham and control groups. Discussion: Coenzyme Q10, an antioxidant agent, can be used as an antioxidant agent in order to reduce the secondary damage in blunt thoracic trauma.

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

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    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.)

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Mechanical ventilation in acute respiratory distress syndrome: The open lung revisited.

    Science.gov (United States)

    Amado-Rodríguez, L; Del Busto, C; García-Prieto, E; Albaiceta, G M

    2017-02-23

    Acute respiratory distress syndrome (ARDS) is still related to high mortality and morbidity rates. Most patients with ARDS will require ventilatory support. This treatment has a direct impact upon patient outcome and is associated to major side effects. In this regard, ventilator-associated lung injury (VALI) is the main concern when this technique is used. The ultimate mechanisms of VALI and its management are under constant evolution. The present review describes the classical mechanisms of VALI and how they have evolved with recent findings from physiopathological and clinical studies, with the aim of analyzing the clinical implications derived from them. Lastly, a series of knowledge-based recommendations are proposed that can be helpful for the ventilator assisted management of ARDS at the patient bedside. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  12. 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.

  13. Diagnostic usefulness of the oedema-infarct ratio to differentiate acute from chronic myocardial damage using magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Kiyoyasu; Suzuki, Susumu; Kinoshita, Kousuke; Yokouchi, Kazuhiko; Iwata, Hirokazu; Sawada, Ken [Gifu Social Insurance Hospital, Department of Cardiology, Gifu (Japan); Isobe, Satoshi; Ohshima, Satoru; Murohara, Toyoaki [Nagoya University Graduate School of Medicine, Department of Cardiology, Nagoya (Japan); Hirai, Makoto [Nagoya University School of Health Sciences, Department of Nursing, Nagoya (Japan)

    2012-04-15

    To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. (orig.)

  14. Acute O 3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment.

    Science.gov (United States)

    Darbah, Joseph N T; Jones, Wendy S; Burton, Andrew J; Nagy, John; Kubiske, Mark E

    2011-09-01

    We studied the effect of high ozone (O(3)) concentration (110-490 nmol mol(-1)) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O(3) pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O(3) exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O(3) and/or CO(2) for 12 years, were harvested. Acute O(3) damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves. Young expanding leaves showed no visible signs of acute O(3) damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O(3) damage as it directly controlled O(3) uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O(3) exposure. Moreover, elevated CO(2) did not ameliorate the adverse effects of acute O(3) dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O(3) levels.

  15. Acute O3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment

    Energy Technology Data Exchange (ETDEWEB)

    Darbah, J.N.; Nagy, J.; Jones, W. S.; Burton, A. J.; Kubiske, M. E.

    2011-10-01

    We studied the effect of high ozone (O{sub 3}) concentration (110-490 nmol mol{sup -1}) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O{sub 3} pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O{sub 3} exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O{sub 3} and/or CO{sub 2} for 12 years, were harvested. Acute O{sub 3} damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves. Young expanding leaves showed no visible signs of acute O{sub 3} damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O{sub 3} damage as it directly controlled O{sub 3} uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O{sub 3} exposure. Moreover, elevated CO{sub 2} did not ameliorate the adverse effects of acute O{sub 3} dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O{sub 3} levels.

  16. Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness

    Directory of Open Access Journals (Sweden)

    Yannick Molgat-Seon

    2017-03-01

    Full Text Available The aim of the present study was to determine whether lung volume recruitment (LVR acutely increases respiratory system compliance (Crs in individuals with severe respiratory muscle weakness (RMW. Individuals with RMW resulting from neuromuscular disease or quadriplegia (n=12 and healthy controls (n=12 underwent pulmonary function testing and the measurement of Crs at baseline, immediately after, 1 h after and 2 h after a single standardised session of LVR. The LVR session involved 10 consecutive supramaximal lung inflations with a manual resuscitation bag to the highest tolerable mouth pressure or a maximum of 50 cmH2O. Each LVR inflation was followed by brief breath-hold and a maximal expiration to residual volume. At baseline, individuals with RMW had lower Crs than controls (37±5 cmH2O versus 109±10 mL·cmH2O−1, p0.05. LVR had no significant effect on measures of pulmonary function at any time point in either group (all p>0.05. During inflations, mean arterial pressure decreased significantly relative to baseline by 10.4±2.8 mmHg and 17.3±3.0 mmHg in individuals with RMW and controls, respectively (both p<0.05. LVR acutely increases Crs in individuals with RMW. However, the high airway pressures during inflations cause reductions in mean arterial pressure that should be considered when applying this technique.

  17. 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

  18. 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.

  19. Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation

    DEFF Research Database (Denmark)

    Johansson, P I; Ostrowski, S R

    2010-01-01

    .e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally......Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i......, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant...

  20. Arterial damages in acute elbow dislocations: which diagnostic tests are required?

    Science.gov (United States)

    Lutter, Christoph; Pfefferkorn, Ronny; Schoeffl, Volker

    2016-07-19

    Blunt vessel injuries of peripheral arteries caused by a direct trauma are rare. Studies have described the frequency of arterial ruptures following closed elbow dislocations in 0.3-1.7% of all cases. However, arterial damage does not always necessarily appear as a complete rupture of the vessel with a loss of peripheral circulation and ischaemic symptoms; a relatively strong periarticular system of collaterals can maintain circulation. Furthermore, the traumatic dislocation can also cause intimal tears, arterial dissections and aneurysms or thrombosis. In all cases of vessel injury, including total disruption, a peripheral pulse might still be palpable. 3 weeks after an acute elbow dislocation, we have diagnosed a patient with a long-segment stenosis of the brachial artery and a thrombosis of the radial artery. Therefore, the close anatomic proximity to the neurovascular structures should always be considered in cases of elbow dislocations, even if peripheral pulses are traceable.

  1. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response

    DEFF Research Database (Denmark)

    Xing, Meichun; Wang, Xiaohui; Palmai-Pallag, Timea;

    2015-01-01

    The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We...... have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81...... is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity....

  2. 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.

  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. 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.

  5. 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.

  6. Selective cyclooxygenase-2 inhibition protects against myocardial damage in experimental acute ischemia

    Directory of Open Access Journals (Sweden)

    Alberto Carnieto Jr.

    2009-03-01

    Full Text Available BACKGROUND: Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. GOAL: The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib could alter the evolution of acute myocardial infarction after reperfusion. METHODS AND RESULTS: This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. CONCLUSION: In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis.

  7. [Ultrastructural changes in the lung in acute adult respiratory distress syndrome].

    Science.gov (United States)

    Szemenyei, K; Széll, K; Kádas, L

    1980-04-01

    Morphological alterations of the lung in respiratory distress syndrome of adults (ARDS) were analyzed in 10 cases with traumatic-and septic shock, laryngitis subglottica descendens and bronchopneumonia. For the better understanding of the pathomechanism of the disease in addition to the standard methods, first of all ultrastructural alterations were studied. Two phases of the morphologic alterations could be distinguished, the phase of the destruction and the phase of the repair. These two processes are not sharply distinguishable. Genesis of the characteristic histological alterations (damage to the epithelial and endothelial cells, formation of hyaline membranes, microcoagulation, proliferation of the type II pneumocytes and fibroblasts, fibrosis) is discussed, with regard to the data of the literature.

  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. A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Le Saux, Claude Jourdan; Davy, Philip; Brampton, Christopher; Ahuja, Seema S; Fauce, Steven; Shivshankar, Pooja; Nguyen, Hieu; Ramaseshan, Mahesh; Tressler, Robert; Pirot, Zhu; Harley, Calvin B; Allsopp, Richard

    2013-01-01

    The emergence of diseases associated with telomere dysfunction, including AIDS, aplastic anemia and pulmonary fibrosis, has bolstered interest in telomerase activators. We report identification of a new small molecule activator, GRN510, with activity ex vivo and in vivo. Using a novel mouse model, we tested the potential of GRN510 to limit fibrosis induced by bleomycin in mTERT heterozygous mice. Treatment with GRN510 at 10 mg/kg/day activated telomerase 2-4 fold both in hematopoietic progenitors ex vivo and in bone marrow and lung tissue in vivo, respectively. Telomerase activation was countered by co-treatment with Imetelstat (GRN163L), a potent telomerase inhibitor. In this model of bleomycin-induced fibrosis, treatment with GRN510 suppressed the development of fibrosis and accumulation of senescent cells in the lung via a mechanism dependent upon telomerase activation. Treatment of small airway epithelial cells (SAEC) or lung fibroblasts ex vivo with GRN510 revealed telomerase activating and replicative lifespan promoting effects only in the SAEC, suggesting that the mechanism accounting for the protective effects of GRN510 against induced lung fibrosis involves specific types of lung cells. Together, these results support the use of small molecule activators of telomerase in therapies to treat idiopathic pulmonary fibrosis.

  10. A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Claude Jourdan Le Saux

    Full Text Available The emergence of diseases associated with telomere dysfunction, including AIDS, aplastic anemia and pulmonary fibrosis, has bolstered interest in telomerase activators. We report identification of a new small molecule activator, GRN510, with activity ex vivo and in vivo. Using a novel mouse model, we tested the potential of GRN510 to limit fibrosis induced by bleomycin in mTERT heterozygous mice. Treatment with GRN510 at 10 mg/kg/day activated telomerase 2-4 fold both in hematopoietic progenitors ex vivo and in bone marrow and lung tissue in vivo, respectively. Telomerase activation was countered by co-treatment with Imetelstat (GRN163L, a potent telomerase inhibitor. In this model of bleomycin-induced fibrosis, treatment with GRN510 suppressed the development of fibrosis and accumulation of senescent cells in the lung via a mechanism dependent upon telomerase activation. Treatment of small airway epithelial cells (SAEC or lung fibroblasts ex vivo with GRN510 revealed telomerase activating and replicative lifespan promoting effects only in the SAEC, suggesting that the mechanism accounting for the protective effects of GRN510 against induced lung fibrosis involves specific types of lung cells. Together, these results support the use of small molecule activators of telomerase in therapies to treat idiopathic pulmonary fibrosis.

  11. Effect of Black Grape Juice against Heart Damage from Acute Gamma TBI in Rats

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    Edson Ramos de Andrade

    2013-09-01

    Full Text Available The aim of this study was to evaluate the potential positive effect of black grape juice (BGJ on lipid peroxidation considering Total Body Irradiation (TBI in Wistar rats. As a potential feasible means of evaluation in situ, blood serum lactate dehydrogenase (LDH levels were evaluated as a marker for heart damage from acute radiation syndrome (ARS. Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation, when they were euthanasiated. LDH on serum and lipid peroxidation on heart tissue were evaluated. High concentration of metabolites from lipid peroxidation in heart, and high LDH level on serum were found only in gamma-irradiated group given placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD analysis, which showed resveratrol as the major constituent. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier.

  12. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

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    Ye Han

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer and analyzed by high performance liquid chromatography (HPLC and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days drastically prevented the elevated activities of aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP and triglyceride (TG in serum and the levels of malondialdehyde (MDA, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β in liver tissue (p < 0.05. Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05. Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

  13. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview

    Science.gov (United States)

    Maléth, József; Hegyi, Péter

    2016-01-01

    Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30–50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca2+ overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca2+ signalling might be beneficial in AP. The inhibition of Ca2+ release from the endoplasmic reticulum or the activity of plasma membrane Ca2+ influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca2+ homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377719

  14. 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.

  15. 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.

  16. Cerium Oxide Nanoparticles Induced Toxicity in Human Lung Cells: Role of ROS Mediated DNA Damage and Apoptosis

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    Sandeep Mittal

    2014-01-01

    Full Text Available Cerium oxide nanoparticles (CeO2 NPs have promising industrial and biomedical applications. In spite of their applications, the toxicity of these NPs in biological/physiological environment is a major concern. Present study aimed to understand the molecular mechanism underlying the toxicity of CeO2 NPs on lung adenocarcinoma (A549 cells. After internalization, CeO2 NPs caused significant cytotoxicity and morphological changes in A549 cells. Further, the cell death was found to be apoptotic as shown by loss in mitochondrial membrane potential and increase in annexin-V positive cells and confirmed by immunoblot analysis of BAX, BCl-2, Cyt C, AIF, caspase-3, and caspase-9. A significant increase in oxidative DNA damage was found which was confirmed by phosphorylation of p53 gene and presence of cleaved poly ADP ribose polymerase (PARP. This damage could be attributed to increased production of reactive oxygen species (ROS with concomitant decrease in antioxidant “glutathione (GSH” level. DNA damage and cell death were attenuated by the application of ROS and apoptosis inhibitors N-acetyl-L- cysteine (NAC and Z-DEVD-fmk, respectively. Our study concludes that ROS mediated DNA damage and cell cycle arrest play a major role in CeO2 NPs induced apoptotic cell death in A549 cells. Apart from beneficial applications, these NPs also impart potential harmful effects which should be properly evaluated prior to their use.

  17. Protective effect of erdosteine metabolite I against hydrogen peroxide-induced oxidative DNA-damage in lung epithelial cells.

    Science.gov (United States)

    Marabini, Laura; Calò, Rossella; Braga, Pier Carlo

    2011-01-01

    It has been shown that the mucolytic agent erdosteine (N-carboxymethylthio-acetyl-homocysteine thiolactone, CAS 84611-23-4) has anti-inflammatory and anti-oxidant properties, and an active metabolite I (MET I) containing pharmacologically active sulphydryl group has been found to have a free radical scavenging activity. The aim of this study was to assess the ability of erdosteine metabolite I to protect A549 human lung adenocarcinoma cell against hydrogen peroxide (H2O2)-mediated oxidative stress and oxidative DNA damage. When A549 cells were pre-treated with the active metabolite I (2.5-5-10 microg/ml) for 10-30 min and then exposed to H2O2 (1-4 mM) for two additional hours at 37 degrees C, 5% at CO2, the intracellular peroxide production, reflected by dichlorofluorescein (DCF) fluorescence, decreased in a concentration-dependent manner. Furthermore, using a comet assay as an indicator for oxidative DNA damage, it was found that the metabolite I prevented damage to cells exposed to shortterm H2O2 treatment. The data suggest that this compound is effective in preventing H2O2-induced oxidative stress and DNA damage in A549 cells. The underlying mechanisms involve the scavenging of intracellular reactive oxygen species (ROS).

  18. Soluble Endothelial Selectin in Acute Lung Injury Complicated by Severe Pneumonia

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    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.

  19. Acute respiratory failure in critically ill patients with interstitial lung disease.

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    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.

  20. 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.

  1. NOD-like receptors in lung diseases

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    Catherine eChaput

    2013-11-01

    Full Text Available The lung is a particularly vulnerable organ at the interface of the body and the exterior environment. It is constantly exposed to microbes and particles by inhalation. The innate immune system needs to react promptly and adequately to potential dangers posed by these microbes and particles, while at the same time avoiding extensive tissue damage. NOD-like receptors (NLRs represent a group of key sensors for microbes and damage in the lung. As such they are important players in various infectious as well as acute and chronic sterile inflammatory diseases, such as pneumonia, chronic obstructive lung disease (COPD, acute lung injury/ARDS, pneumoconiosis and asthma. Activation of most known NLRs leads to the production and release of pro-inflammatory cytokines, and/or to the induction of cell death. We will review NLR functions in the lung during infection and sterile inflammation.

  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

    Objective: To investigate the effect of anisodamine combining with conventional ther-apy on the degree of lung injury and inflammatory reaction of patients with acute pul-monary contusion. Methods: A total of 48 patients with acute pulmonary contusion treated in our hospital emergency department from April 2011 to October 2015 were enrolled as the research object and were divided into experimental group and control group by using a method of random number table. Experimental group received anisodamine combining with con-ventional therapy and control group received conventional therapy. In the process of the treatment, the mechanical ventilation time, hospital stays in intensive care unit and the number of cases developed into acute respiratory distress syndrome and multiple organ dysfunction syndromes of patients in two groups were observed. Oxygenation indexes of patients were respectively calculated on Days 1, 2 and 3 after treatment. The contents of inflammatory mediators in serum were detected on Day 3 after treatment. Results: The mechanical ventilation time and hospital stays in intensive care unit [(9.52 ± 1.41) vs. (14.57 ± 2.51) days] of patients in experimental group were signifi-cantly shorter than those in control group, and the number of cases developed into acute respiratory distress syndrome [1 (4.17%) vs. 9 (37.50%)] and multiple organ dysfunction syndrome [1 (4.17%) vs. 7 (29.17%)] was significantly less than those in control group. Oxygenation indexes (294.52 ± 41.26 vs. 257.63 ± 38.52; 357.74 ± 47.74 vs. 279.87 ± 31.46; 396.71 ± 55.12 vs. 279.87 ± 31.46) of patients were respectively calculated on Days 1, 2 and 3 after treatment, which were significantly higher than those in the control group. On Day 3 after treatment, the contents of serum C-reactive protein [(7.94 ± 1.05) vs. (14.49 ± 2.97) mg/L], tumor necrosis factor a [(264.69 ± 41.58) vs. (417.87 ± 64.51) ng/L], interleukin-6 (IL-6) [(147.72 ± 21.36) vs. (257.68 ± 41.54) ng

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

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    Nan-Bin Yu

    2016-09-01

    Full Text Available Objective: To investigate the effect of anisodamine combining with conventional therapy on the degree of lung injury and inflammatory reaction of patients with acute pulmonary contusion. Methods: A total of 48 patients with acute pulmonary contusion treated in our hospital emergency department from April 2011 to October 2015 were enrolled as the research object and were divided into experimental group and control group by using a method of random number table. Experimental group received anisodamine combining with conventional therapy and control group received conventional therapy. In the process of the treatment, the mechanical ventilation time, hospital stays in intensive care unit and the number of cases developed into acute respiratory distress syndrome and multiple organ dysfunction syndromes of patients in two groups were observed. Oxygenation indexes of patients were respectively calculated on Days 1, 2 and 3 after treatment. The contents of inflammatory mediators in serum were detected on Day 3 after treatment. Results: The mechanical ventilation time and hospital stays in intensive care unit [(9.52 ± 1.41 vs. (14.57 ± 2.51 days] of patients in experimental group were signifi- cantly shorter than those in control group, and the number of cases developed into acute respiratory distress syndrome [1 (4.17% vs. 9 (37.50%] and multiple organ dysfunction syndrome [1 (4.17% vs. 7 (29.17%] was significantly less than those in control group. Oxygenation indexes (294.52 ± 41.26 vs. 257.63 ± 38.52; 357.74 ± 47.74 vs. 279.87 ± 31.46; 396.71 ± 55.12 vs. 279.87 ± 31.46 of patients were respectively calculated on Days 1, 2 and 3