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Sample records for acute lung damage

  1. Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy

    Kao, Kuo-Chin; Hu, Han-Chung; Chang, Chih-Hao; Hung, Chen-Yiu; Chiu, Li-Chung; Li, Shih-Hong; Lin, Shih-Wei; Chuang, Li-Pang; Wang, Chih-Wei; Li, Li-Fu; Chen, Ning-Hung; Yang, Cheng-Ta; Huang, Chung-Chi; Tsai, Ying-Huang

    2015-01-01

    Introduction Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS), however, the presence of DAD in the clinical criteria of ARDS patients by Berlin definition is little known. This study is designed to investigate the role of DAD in ARDS patients who underwent open lung biopsy. Methods We retrospectively reviewed all ARDS patients who met the Berlin definition and underwent open lung biopsy from January 1999 to January 2014 in a referred med...

  2. Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury

    Silva, Pedro L; Cruz, Fernanda F.; Fujisaki, Livia C; Gisele P. Oliveira; Samary, Cynthia S; Ornellas, Debora S; Maron-Gutierrez, Tatiana; Rocha, Nazareth N.; Goldenberg, Regina; Garcia, Cristiane SNB; MARCELO M. MORALES; Vera L. Capelozzi; Gama de Abreu, Marcelo; Pelosi, Paolo; Rocco, Patricia RM

    2010-01-01

    Introduction Recruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury ...

  3. Spectroscopic Approach to Capillary-Alveolar Membrane Damage Induced Acute Lung Injury

    Jing Wang

    1999-01-01

    Full Text Available BACKGROUND: Acute (or adult respiratory distress syndrome (ARDS is often associated with a high mortality rate in the critical care population. The term acute lung injury (ALI, a primitive phase of ARDS, was introduced by the European and American consensus groups to provide early diagnoses of ARDS. The pathophysiological characterization of ALI/ARDS – an increased pulmonary capillary-alveolar membrane barrier permeability – is generally not included in current intensive care unit diagnosis criteria.

  4. Noninvasive assessment of peroxidative lung damage by HIPDM lung scanning

    Miniati, M.; Borrelli, E.; Monti, S.; Cocci, F.; Solfanelli, S.; Giani, L.; Pistolesi, M. (Univ. of Pisa (Italy) Univ. of Siena, (Italy))

    1991-03-15

    The basic compound iodobenzyl-propanediamine (HIPDM), when given intravenously, is extracted by the lungs whence it is effluxed at a slow exponential rate. In humans (normal non smokers), the mean residence time ({bar t}) of 123I-HIPDM, assessed by external detection, averages 7.2 {plus minus} 1.1 hrs. Persistence of HIPDM in lungs is significantly increased in asymptomatic smokers and, to a greater extent, in patients with ARDS. Since production of free oxygen radicals reportedly occurs as a consequence of smoke exposure and in the course of acute lung injury, the authors hypothesized that the prolonged persistence of HIPDM in the lungs of smokers and of patients with ARDS might reflect a peroxidative damage of lung tissue. They tested this hypothesis in rabbits since their baseline HIPDM lung clearance is similar to that of nonsmoking humans. In rabbits, acute lung injury was induced by phorbol myristate acetate. Three hrs after PMA administration, the animals received an i.v. bolus of {sup 131}I-HIPDM. Radioactivity over the chest was recorded for 2 hrs by gamma camera and HIPDM mean residence time in the lungs was computed. Thereafter, the animals were sacrificed and their lungs were removed to measure wet/dry weight ratio as index of lung edema and malondialdehyde (MDA) content as index of lipid peroxidation. HIPDM mean residence time was positively correlated with MDA level in lung tissue, but not with wet/dry weight ratio. Noninvasive assessment of HIPDM lung kinetics may then serve as specific in vivo marker of peroxidative lung injury.

  5. Lung Injury in Acute Pancreatitis

    Raffaele Pezzilli; Lara Bellacosa; Cristina Felicani

    2009-01-01

    Most knowledge has been accumulated on the mechanisms involved in the development of distant organ injuries during the course of severe acute pancreatitis. Among the various distant organ dysfunctions, both the development of acute lung injury and acute respiratory distress syndrome represent serious complications. In the following paragraphs the pathophysiological mechanisms capable of determining lung injury during the course of acute pancreatitis will be reviewed. Pancreatic Enzymes and...

  6. Bilirubin influence on oxidative lung damage and surfactant surface tension properties

    Dani C.; Martelli E.; Tronchin M.; Buonocore G.; Longini M.; Di Filippo A; Giossi M.; Rubaltelli F.F.

    2004-01-01

    To study the hypothesis that hyperbilirubinemia might reduce in vivo oxidative lung damage while also diminishing lung surfactant surface tension properties during acute lung injury, we performed a randomized study in a rabbit model of acute lung injury. Twenty rabbits were randomized to receive bilirubin or saline intravenously. Acute lung injury was induced by lung lavages with saline. Lung tissue oxidation was evaluated by measuring total hydroperoxide (TH), advanced oxidation protein prod...

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

    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.

  8. Biomarkers in Acute Lung Injury

    Bhargava, Maneesh; Wendt, Chris

    2012-01-01

    Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) result in high permeability pulmonary edema causing hypoxic respiratory failure with high morbidity and mortality. As the population ages, the incidence of ALI is expected to rise. Over the last decade, several studies have identified biomarkers in plasma and bronchoalveolar lavage fluid providing important insights into the mechanisms involved in the pathophysiology of ALI. Several biomarkers have been validated in subjec...

  9. Cell kinetics and acute lung injury

    In order to estimate whether acute lung injury is followed by a stereotype pattern of cell proliferation in the lungs, mice were treated with three cytostatic drugs: cyclophosphamide, busulfan, or 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU). The alveolar labeling index was measured following drug administration with a pulse of 3H-labeled thymidine and autoradiography. In cyclophosphamide treated animals, peak alveolar cell proliferation was seen 5 days after injection of the drug. In animals treated with busulfan or BCNU, proliferation was even more delayed (occurring 2 to 3 wks after administration). In contrast, with oleic acid, the highest alveolar cell labeling was found 2 days after intravenous administration. In animals exposed to a cytostatic drug, proliferation of type II alveolar cells was never a prominent feature; whereas, in animals treated with oleic acid there was an initial burst of type II cell proliferation. It was concluded that the patterns of pulmonary repair vary between chemical designed to interfere with DNA replication as compared to agents which produce acute lung damage such as oleic acid

  10. Transfusion related acute lung injury

    Sharma Ratti; Bhattacharya Prasun; Thakral Beenu; Saluja Karan; Marwaha Neelam

    2009-01-01

    Transfusion related acute lung injury (TRALI) is an uncommon but potentially fatal adverse reaction to transfusion of plasma containing blood components. We describe a case of 10-year-old male child with aplastic anemia, platelet count of 7800/΅l, B positive blood group who developed fever (39.2΀C), difficulty in breathing and cyanosis within 2 hrs after transfusion of a random platelet concentrate. Despite the best resuscitative efforts, the child died within next 24 hrs. The prese...

  11. Evolution of endotoxin induced acute lung injury in the rat.

    Domenici-Lombardo, L.; C. Adembri; Consalvo, M.; Forzini, R.; Meucci, M.; Romagnoli, P; Novelli, G.P.

    1995-01-01

    To clarify the evolution of acute lung injury induced by endotoxin, the progression of lung damage in 26 rats submitted to intratracheal instillation of 5 mg/kg body weight endotoxin was examined by blood gas analysis, computerized tomography, light and electron microscopy. Hypoxaemia, hypercapnia, acidosis and inhomogeneous bilateral infiltrates developed gradually within 48 hours. Monocytes appeared within blood capillaries and the instertitium by 12 hours after treatment, then migrated int...

  12. Pathogenesis of acute lung injury in severe acute pancreatitis

    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.

  13. Transfusion related acute lung injury

    Sharma Ratti

    2009-10-01

    Full Text Available Transfusion related acute lung injury (TRALI is an uncommon but potentially fatal adverse reaction to transfusion of plasma containing blood components. We describe a case of 10-year-old male child with aplastic anemia, platelet count of 7800/΅l, B positive blood group who developed fever (39.2΀C, difficulty in breathing and cyanosis within 2 hrs after transfusion of a random platelet concentrate. Despite the best resuscitative efforts, the child died within next 24 hrs. The present case highlights the fact that TRALI should be kept as a differential diagnosis in all patients developing acute respiratory discomfort within 6 hrs of transfusion. Without a ′gold standard′ the diagnosis of TRALI relies on a high index of suspicion and on excluding other types of transfusion reactions. Notification to transfusion services is crucial to ensure that a proper investigation is carried out and at-risk donor and recipients can be identified, and risk reduction measures can be adopted.

  14. Disseminated tuberculosis presenting as acute lung injury

    Mary Grace

    2014-01-01

    Full Text Available Tuberculosis presenting as acute lung injury is distinctly uncommon, even in India where tuberculosis an endemic disease. Simultaneously, acute lung injury is a highly fatal complication of tuberculosis. A high index of suspicion is needed to diagnose tuberculosis in such cases. Failure to initiate early treatment can have disastrous consequences as exemplified in this case report. This case attempts to highlight the need to consider tuberculosis as one of the likely causative factors for acute lung injury and the importance of starting empirical antituberculous therapy in suspected cases early.

  15. Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome

    Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Paul R. Knight; Notter, Robert H.

    2008-01-01

    Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, a...

  16. Disseminated tuberculosis presenting as acute lung injury

    Mary Grace; V K Shameer; Renjith Bharathan; Kavitha Chandrikakumari

    2014-01-01

    Tuberculosis presenting as acute lung injury is distinctly uncommon, even in India where tuberculosis an endemic disease. Simultaneously, acute lung injury is a highly fatal complication of tuberculosis. A high index of suspicion is needed to diagnose tuberculosis in such cases. Failure to initiate early treatment can have disastrous consequences as exemplified in this case report. This case attempts to highlight the need to consider tuberculosis as one of the likely causative factors for acu...

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

    JM Real; MM. Marques; GMGT Spilborghs; EM Negri; MM Matzuk; RP Moura; AA Camargo; Deheinzelin, D; AAM Dias

    2008-01-01

    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 obje...

  18. Resolution of acute inflammation in the lung.

    Levy, Bruce D; Serhan, Charles N

    2014-01-01

    Acute inflammation in the lung is essential to health. So too is its resolution. In response to invading microbes, noxious stimuli, or tissue injury, an acute inflammatory response is mounted to protect the host. To limit inflammation and prevent collateral injury of healthy, uninvolved tissue, the lung orchestrates the formation of specialized proresolving mediators, specifically lipoxins, resolvins, protectins, and maresins. These immunoresolvents are agonists for resolution that interact with specific receptors on leukocytes and structural cells to blunt further inflammation and promote catabasis. This process appears to be defective in several common lung diseases that are characterized by excess or chronic inflammation. Here, we review the molecular and cellular effectors of resolution of acute inflammation in the lung. PMID:24313723

  19. Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites.

    Till, G O; Johnson, K J; R. Kunkel; Ward, P. A.

    1982-01-01

    Intravascular activation of the complement system with cobra venom factor results in acute lung injury, which has been quantitated by increases in lung vascular permeability. Cobra venom factor preparations devoid of phospholipase A2 activity retain full lung-damaging capacity. The lung injury is associated with the preceding appearance of chemotactic activity in the serum coincident with the development of a profound neutropenia. The chemotactic activity is immunochemically related to human ...

  20. Transfusion related acute lung injury (TRALI)

    TAJANA ZAH; JASNA MESARIC; VISNJA MAJERIC-KOGLER

    2009-01-01

    Transfusion-related acute lung injury (TRALI) is a complication following transfusion of blood products and is potentially a life-threatening adverse event of transfusion. The first case of fatal pulmonary edema following transfusion was reported in the 1950s. In recent time, TRALI has developed from an almost unknown transfusion reaction to the most common cause of transfusion related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute res...

  1. Obstructive lung disease in acute medical patients.

    Seemungal, T.; Harrinarine, R.; Rios, M.; Abiraj, V.; Ali, A.; Lacki, N.; Mahabir, N.; Ramoutar, V.; King, C. P.; Bhowmik, A.; Wedzicha, J A

    2008-01-01

    OBJECTIVES: To determine the proportion of adult medical patients who have chronic obstructive pulmonary disease (COPD), using the Global initiative for Chronic Obstructive Lung Disease guidelines (GOLD), and its relation to vascular disease. METHODS: This is a prospective cross-sectional study of adult patients admitted to acute medical wards. Interviewer administered questionnaire, anthropometric and spirometric measurements were done. RESULTS: Spirometry was performed in 720 acute admissio...

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

    Sepehr, Reyhaneh; Audi, Said H.; Maleki, Sepideh; Staniszewski, Kevin; EIS, ANNIE L.; Konduri, Girija G.; Ranji, Mahsa

    2013-01-01

    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 damag...

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

    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

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

    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. Lung oxidative response after acute coal dust exposure

    Coal dust exposure can induce an acute alveolar and interstitial inflammation that can lead to chronic pulmonary diseases. The objective of this study was to describe the acute and later effects of acute coal dust exposure in lung parenchyma and the involvement of reactive oxygen species in coal dust effects. Forty-eight male Wistar rats (200-250 mg) were separated into four groups: 48 h, 7 days, 30 days, and 60 days after coal dust instillation. Gross mineral coal dust (3 mg/0.5 mL saline) was administered directly in the lungs of the treatment group by intratracheal instillation. Control animals received only saline solution (0.5 mL). Lipid peroxidation was determined by the quantity of thiobarbituric acid-reactive species (TBARS), oxidative damage to protein was obtained by the determination of carbonyl groups, the total radical-trapping antioxidant parameter (TRAP) was estimated by luminol chemoluminescence emission, catalase activity was measured by the rate of decrease in hydrogen peroxide, and superoxide dismutase activity was assayed by the inhibition of adrenaline autooxidation. Histological evaluation of coal dust-treated rats demonstrated an inflammatory infiltration after 48 h of the exposure. Initially, this was a cellular infiltration suggestive of lymphocyte infiltration with lymphoid hyperplasia that remained until 7 days after induction. This initial response was followed by a chronic inflammatory infiltration characterized by aggregates of macrophages 30 days after induction. This inflammatory response tended to resolve 60 days after induction, being similar to that of control animals. During both the acute and chronic phases of lung inflammation we observed a decrease in the TRAP in the lung of coal dust-exposed animals compared to that in control animals. We also observed an activation of superoxide dismutase 60 days after coal dust exposition. TBARS were increased 60 days after coal dust exposure and protein carbonyl groups increased at all

  6. Pathophysiology of pulmonary hypertension in acute lung injury

    Price, Laura C.; Mcauley, Danny F.; Marino, Philip S; Finney, Simon J; Griffiths, Mark J.; Wort, Stephen John

    2012-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung p...

  7. Human models of acute lung injury

    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.

  8. Transfusion-Related Acute Lung Injured (TRALI): Current Concepts

    Álvarez, P; Carrasco, R; Romero-Dapueto, C; Castillo, R.L

    2015-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated...

  9. Transfusion-related acute lung injury

    Dixit Ramakant; Sharma Sidharth; Parmez A

    2010-01-01

    Transfusion-related acute lung injury (TRALI) is related to the transfusion of blood components. Typically, it is a clinical syndrome, characterized by the sudden onset of dyspnea, hypoxemia and bilateral non-cardiogenic pulmonary edema. A 83-year-old female patient with a history of AML developed TRALI after receiving 6 units of platelets. TRALI symptoms was started 10 min later the transfusion. AML is a risky group for TRALI. While giving transfusion to the risky groups of TRALI one must be...

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

    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.

  11. Transfusion Related Acute Lung Injury -A Case Report

    Anamika,; Vasanth Nayak; Jose Chacko; G Parameswara

    2008-01-01

    Transfusion related acute lung injury (TRALI) is a rare but life threatening complication of blood transfusion which is being increasingly recognized. It is caused by cross reaction between donor antibodies and host leucocytes or between donor leucocytes with host antibodies. TRALI usually presents as an Acute Lung Injury (ALI) resulting in pulmonary congestion and edema, often leading to Acute Respiratory Distress Syndrome (ARDS). We report a case of TRALI in a patient who underwent laparoto...

  12. Acute Rejection and Humoral Sensitization in Lung Transplant Recipients

    Martinu, Tereza; Chen, Dong-Feng; Palmer, Scott M

    2009-01-01

    Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent develop...

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

    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....

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

    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....

  15. Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

    Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using ...

  16. Serine/threonine kinase-protein kinase B and extracellular signal-regulated kinase regulate ventilator-induced pulmonary fibrosis after bleomycin-induced acute lung injury: a prospective, controlled animal experiment

    Li, Li-Fu; Liao, Shuen-Kuei; Huang, Chung-Chi; Hung, Ming-Jui; Quinn, Deborah A

    2008-01-01

    Introduction Lung fibrosis, reduced lung compliance, and severe hypoxemia found in patients with acute lung injury often result in a need for the support of mechanical ventilation. High-tidal-volume mechanical ventilation can increase lung damage and fibrogeneic activity but the mechanisms regulating the interaction between high tidal volume and lung fibrosis are unclear. We hypothesized that high-tidal-volume ventilation increased pulmonary fibrosis in acute lung injury via the serine/threon...

  17. Acute Lung Injury Due To Carbon Monoxide Exposure

    Uzkeser M et al.

    2012-10-01

    Full Text Available A 20-year-old woman, who was found unconscious in the bed by the morning, was brought to emergency department. Her carboxyhemoglobin level was 20.2%. The portable chest X-ray showed bilaterally alveolar and interstitial infiltration. Initial pO 2 /FIO 2 ratio was calculated as 119 mmHg. Acute lung injury due to carbon monoxide intoxication was considered. She was intubated and mechanical ventilation was applied. In the second day of hospitalization, a clear improvement was observed on the chest X-ray. She was discharged without any complication on the seventh day of hospitalization. Early diagnosis and treatment may prevent progression of ARDS and progression of permanent damage, and may lead to complete recovery.

  18. Transfusion related acute lung injury (TRALI

    TAJANA ZAH

    2009-10-01

    Full Text Available Transfusion-related acute lung injury (TRALI is a complication following transfusion of blood products and is potentially a life-threatening adverse event of transfusion. The first case of fatal pulmonary edema following transfusion was reported in the 1950s. In recent time, TRALI has developed from an almost unknown transfusion reaction to the most common cause of transfusion related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress which has temporal association with transfusion of blood components. In 2008 a distinction between classic and delayed syndrome was proposed. However, pathophysiology of TRALI still remains controversial. A number of different models were proposed to explain the pathogenesis. The two, presently most accepted models, are not mutually exclusive. The first is the antibody mediated model and the second is the two-event model.In this review article the definition of TRALI, patient predisposition, treatment, prevention and reporting guidelines are examined. The current knowledge on the topic TRALI is summarized.

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

    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.

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

    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

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

    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.

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

    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

  3. Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury

    Deqing Wu; Yue Zeng; Yuting Fan; Jianghong Wu; Tunike Mulatibieke; Jianbo Ni; Ge Yu; Rong Wan; Xingpeng Wang; Guoyong Hu

    2016-01-01

    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 regula...

  4. Experimental Models of Transfusion-Related Acute Lung Injury (TRALI)

    Gilliss, Brian M.; Looney, Mark R.

    2011-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approache...

  5. Adult Stem Cells for Acute Lung Injury: Remaining Questions & Concerns

    Zhu, Ying-Gang; Hao, Qi; Monsel, Antoine; Feng, Xiao-mei; Lee, Jae W.

    2013-01-01

    Acute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary edema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple pre-clinical studies, adult stem cells h...

  6. Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury

    Shaver, Ciara M.; Grove, Brandon S.; Clune, Jennifer K.; Nigel Mackman; Lorraine B. Ware; Bastarache, Julie A

    2016-01-01

    Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-indu...

  7. Role of Chemokines in the Pathogenesis of Acute Lung Injury

    Bhatia, Madhav; Zemans, Rachel L.; Jeyaseelan, Samithamby

    2012-01-01

    Acute lung injury (ALI) is due to an uncontrolled systemic inflammatory response resulting from direct injury to the lung or indirect injury in the setting of a systemic process. Such insults lead to the systemic inflammatory response syndrome (SIRS), which includes activation of leukocytes—alveolar macrophages and sequestered neutrophils—in the lung. Although systemic inflammatory response syndrome is a physiologic response to an insult, systemic leukocyte activation, if excessive, can lead ...

  8. Subclinical interstitial lung damage in workers exposed to indium compounds

    Choi, Sungyeul; Won, Yong-Lim; Kim, Dohyung; Yi, Gwang-Yong; Park, Jai-Soung; Kim, Eun-A

    2013-01-01

    Objectives The present study was designed to determine whether there is a relationship between indium compound exposure and interstitial lung damage in workers employed at indium tin oxide manufacturing and reclaiming factories in Korea. Methods In 2012, we conducted a study for the prevention of indium induced lung damage in Korea and identified 78 workers who had serum indium or Krebs von den Lungen-6 (KL-6) levels that were higher than the reference values set in Japan (3 μg/L and 500 U/mL...

  9. Lung damages in mice and rats with thoracic irradiation

    Irradiation of the lung can produce serious tissue disruption and result in significant, potentially fatal pulmonary dysfunction. The sterilization of tumours in the lung is often limited by the clinical tolerance of the normal lung tissues. Many experiments have been carried out so far in order to elucidate the lung damages with thoracic irradiation. Earlier lung damages are an increase of alveolar surfactant, an induced proliferation of type II pneumocytes and dysfunctions in capillary endothelial cells. The increased amounts of alveolar surfactant were measurable by 24 hours beyond 10 Gy. Labelling indices of type II pneumocytes with tritiated thymidine have a peak at about 4 weeks after irradiation. Pulmonary angiotensin converting enzyme activity, plasminogen activator activity, and prostacyclin and thromboxane production served as indices of lung endothelial function. There were dose-dependent decrease in angiotensin converting enzyme and plasminogen activator activity and increases in prostacyclin and thromoboxane production at two months after irradiation. Radiation pneumonitis as a late effect appears at approximately 20 weeks after irradiation. An increase of breathing rates was observed at the time of pneumonitis. Animals which survived pneumonitis may suffer from lung fibrosis beyond one year after irradiation. RBEs of fast neutrons and negative pions were reported to be between 1 and 6 depending upon indices of effects and upon exposure patterns. (author)

  10. Measuring dead-space in acute lung injury.

    Kallet, R H

    2012-11-01

    Several recent studies have advanced our understanding of dead-space ventilation in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). They have demonstrated the utility of measuring physiologic dead-space-to-tidal volume ratio (VD/VT) and related variables in assessing outcomes as well as therapeutic interventions. These studies have included the evaluation of mortality risk, pulmonary perfusion, as well as the effectiveness of drug therapy, prone positioning, positive end-expiratory pressure (PEEP) titration, and inspiratory pattern in improving gas exchange. In patients with ALI/ARDS managed with lung-protective ventilation a significant relationship between elevated VD/VT and increased mortality continues to be reported in both early and intermediate phases of ALI/ARDS. Some clinical evidence now supports the suggestion that elevated VD/VT in part reflects the severity of pulmonary vascular endothelial damage. Monitoring VD/VT also appears useful in assessing alveolar recruitment when titrating PEEP and may be a particularly expedient method for assessing the effectiveness of prone positioning. It also has revealed how subtle manipulations of inspiratory time and pattern can improve CO(2) excretion. Much of this has been accomplished using volumetric capnography. This allows for more sophisticated measurements of pulmonary gas exchange function including: alveolar VD/VT, the volume of CO(2) excretion and the slope of the alveolar plateau which reflects ventilation: perfusion heterogeneity. Many of these measurements now can be made non-invasively which should only increase the research and clinical utility of volumetric capnography in studying and managing patients with ALI/ARDS. PMID:22858884

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

    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

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

    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

  13. Lung tissue remodeling in the acute respiratory distress syndrome

    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.

  14. Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

    Koeppen, Michael; Eckle, Tobias; Eltzschig, Holger K.

    2011-01-01

    Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exch...

  15. Melatonin reduces acute lung injury in endotoxemic rats

    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

  16. Evaluation of Arsenic Trioxide Potential for Lung Cancer Treatment: Assessment of Apoptotic Mechanisms and Oxidative Damage

    Walker, Alice M; Stevens, Jacqueline J; Ndebele, Kenneth; Tchounwou, Paul B

    2016-01-01

    Background Lung cancer is one of the most lethal and common cancers in the world, causing up to 3 million deaths annually. The chemotherapeutic drugs that have been used in treating lung cancer include cisplatin-pemetrexed, cisplastin-gencitabinoe, carboplatin-paclitaxel and crizotinib. Arsenic trioxide (ATO) has been used in the treatment of acute promyelocytic leukemia. However, its effects on lung cancer are not known. We hypothesize that ATO may also have a bioactivity against lung cancer, and its mechanisms of action may involve apoptosis, DNA damage and changes in stress-related proteins in lung cancer cells. Methods To test the above stated hypothesis, lung carcinoma (A549) cells were used as the test model. The effects of ATO were examined by performing 6-diamidine-2 phenylindole (DAPI) nuclear staining for morphological characterization of apoptosis, flow cytometry analysis for early apoptosis, and western blot analysis for stress-related proteins (Hsp70 and cfos) and apoptotic protein expressions. Also, the single cell gel electrophoresis (Comet) assay was used to evaluate the genotoxic effect. Results ATO-induced apoptosis was evidenced by chromatin condensation and formation of apoptotic bodies as revealed by DAPI nuclear staining. Cell shrinkage and membrane blebbing were observed at 4 and 6 µg/ml of ATO. Data from the western blot analysis revealed a significant dose-dependent increase (p < 0.05) in the Hsp 70, caspase 3 and p53 protein expression, and a significant (p < 0.05) decrease in the cfos, and bcl-2 protein expression at 4 and 6 µg/ml of ATO. There was a slight decrease in cytochrome c protein expression at 4 and 6 µg/ ml of ATO. Comet assay data revealed significant dose-dependent increases in the percentages of DNA damage, Comet tail lengths, and Comet tail moment. Conclusion Taken together our results indicate that ATO is cytotoxic to lung cancer cells and its bioactivity is associated with oxidative damage, changes in cellular

  17. Role of C3, C5 and Anaphylatoxin Receptors in Acute Lung Injury and in Sepsis

    Bosmann, Markus; Ward, Peter A.

    2012-01-01

    The complement system plays a major role in innate immune defenses against infectious agents, but exaggerated activation of complement can lead to severe tissue injury. Systemic (intravascular) activation of complement can, via C5a, lead to neutrophil (PMN) activation, sequestration and adhesion to the pulmonary capillary endothelium, resulting in damage and necrosis of vascular endothelial cells and acute lung injury (ALI). Intrapulmonary (intraalveolar) activation of complement can cause AL...

  18. NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury.

    Yang Li

    Full Text Available Glutamate is a major neurotransmitter in the central nervous system (CNS. Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR, causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice.C57BL/6 mice were intratracheally injected with bleomycin (BLM to induce lung injury. Mice were randomized to receive saline, memantine (Me, BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation.BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils.Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice.

  19. Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

    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.

  20. Acute pulmonary rejection in heart and lung transplant recipients

    Acute pulmonary rejection occurs in up to 50% of patients undergoing heart and lung transplant procedures. These patients are also susceptible to volume overload and pneumonia. To evaluate the radiographic and high-resolution CT appearances of acute pulmonary rejection, we compared chest radiographs and high-resolution CT scans with the clinical findings and with histologic and lavage data from 91 serial transbronchial biopsies in 13 patients. The radiographic appearance of acute pulmonary rejection is characterized by prominent septal lines and pleural effusions. The authors conclude that in the appropriate clinical setting, the appearance of new pleural effusions and prominent septal lines is highly suggestive of acute pulmonary rejections

  1. Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity

    Golson Maria L

    2005-06-01

    Full Text Available Abstract Background Acute RT-induced damage to the lung is characterized by inflammatory changes, which proceed to the development of fibrotic lesions in the late phase of injury. Ultimately, complete structural ablation will ensue, if the source of inflammatory / fibrogenic mediators and oxidative stress is not removed or attenuated. Therefore, the purpose of this study is to determine whether overexpression of extracellular superoxide dismutase (EC-SOD in mice ameliorates acute radiation induced injury by inhibiting activation of TGFβ1 and downregulating the Smad 3 arm of its signal transduction pathway. Methods Whole thorax radiation (single dose, 15 Gy was delivered to EC-SOD overexpressing transgenic (XRT-TG and wild-type (XRT-WT animals. Mice were sacrificed at 1 day, 1 week, 3, 6, 10 and 14 weeks. Breathing rates, right lung weights, total/differential leukocyte count, activated TGFβ1 and components of its signal transduction pathway (Smad 3 and p-Smad 2/3 were assessed to determine lung injury. Results Irradiated wild-type (XRT-WT animals exhibited time dependent increase in breathing rates and right lung weights, whereas these parameters were significantly less increased (p vs. XRT-WT. Conclusion This study shows that overexpression of EC-SOD confers protection against RT-induced acute lung injury. EC-SOD appears to work, in part, via an attenuation of the macrophage response and also decreases TGFβ1 activation with a subsequent downregulation of the profibrotic TGFβ pathway.

  2. Genetic damage in multiple organs of acutely exercised rats.

    Pozzi, Renan; Rosa, Jose C; Eguchi, Ricardo; Oller do Nascimento, Claudia M; Oyama, Lila M; Aguiar, Odair; Chaves, Marcelo D; Ribeiro, Daniel A

    2010-12-01

    The aim of this study was to investigate the effects of acute exercise on genomic damage in an animal model. Male adult Wistar rats were divided into the following groups: control and acute exercised (experimental). For this purpose, 15 animals were accustomed to running on a rodent treadmill for 15 min per day for 5 days (10-20 m min(-1); 08 grade). After 4 days at rest, active animals ran on the treadmill (22 m min(-1), 58 grade) till exhaustion. Cells from peripheral blood, liver, heart, and brain were collected after 0, 2, and 6 h after exercise. The results showed that acute exercise was able to induce genetic damage in peripheral blood cells after 2 and 6 h of exercise, whereas liver pointed out genetic damage for all periods evaluated. No genetic damage was induced either in brain or in heart cells. In conclusion, our results suggest that acute exercise could contribute to the genetic damage in peripheral blood and liver cells. It seems that liver is a sensitive organ to the genotoxic insult after acute exercise. PMID:20979236

  3. Protective Effect of Curcumin on Endotoxin-induced Acute Lung Injury in Rats

    2006-01-01

    To investigate the protective effect of curcumin on endotoxin-induced acute lung injury in rats, and explore the underlying mechanisms, 24 male Wistar rats were randomly divided into 4 experimental groups: sham-vehicle (S), sham-curcumin (C), lipopolysaccharide (LPS)-vehicle (L), and curcumin-lipopolysaccharide (C-L) groups. The wet/dry (W/D) weight ratio of the lung and bronchoalveolar lavage (BAL) fluid protein content were used as measures of lung injury. Neutrophil recruitment and activation were evaluated by BAL fluid cellularity and myeloperoxidase (MPO) activity in cell-free BAL and lung tissue. The levels of cytokine-induced neutrophil chemoattractant-1(CINC-1) in lung tissues were measured by ELISA. The histopathological changes of lung tissues were observed by using the HE staining. Our results showed that lung injury parameters, including the wet/dry weight ratio and protein content in BALF, were significantly higher in the L group than in the S group (P<0.01). In the L group, higher numbers of neutrophils and greater MPO activity in cell-free BAL and lung homogenates were observed when compared with the S group (P<0.01).There was a marked increase in CINC-1 levels in lung tissues in response to LPS challenge (P<0.01,L group vs S group). Curcumin pretreatment significantly attenuated LPS-induced changes in these indices. LPS caused extensive morphological lung damage, which was also lessened after curcumin pretreatment. All the above-mentioned parameters in the C group were not significantly different from those of the S group. It is concluded that curcumin pretreatment attenuates LPS-induced lung injury in rats. This beneficial effect of curcumin may involves, in part, inhibition of neutrophilic recruitment and activity, possibly through inhibition of lung CINC-1 expression.

  4. Transfusion Related Acute Lung Injury -A Case Report

    Anamika

    2008-01-01

    Full Text Available Transfusion related acute lung injury (TRALI is a rare but life threatening complication of blood transfusion which is being increasingly recognized. It is caused by cross reaction between donor antibodies and host leucocytes or between donor leucocytes with host antibodies. TRALI usually presents as an Acute Lung Injury (ALI resulting in pulmonary congestion and edema, often leading to Acute Respiratory Distress Syndrome (ARDS. We report a case of TRALI in a patient who underwent laparotomy for ruptured corpus luteal cyst requiring blood transfusion. She presented with acute pulmonary edema about an hour after commencing a blood transfusion .This was managed conservatively with oxygen, steroids and diuretics. Patient improved rapidly and later discharged without any residual complications.

  5. Biochemical detection of type I cell damage after nitrogen dioxide-induced lung injury in rats.

    McElroy, M C; Pittet, J F; Allen, L; Wiener-Kronish, J P; Dobbs, L G

    1997-12-01

    We have previously shown that injury to lung epithelial type I cells can be detected biochemically by measuring the airway fluid content of a type I cell-specific protein, rTI40, in a model of severe acute lung injury [M. C. McElroy, J.-F. Pittet, S. Hashimoto, L. Allen, J. P. Wiener-Kronish, and L. G. Dobbs. Am. J. Physiol. 268 (Lung Cell. Mol. Physiol. 12): L181-L186, 1995]. The first objective of the present study was to evaluate the utility of rTI40 in the assessment of alveolar injury in a model of milder acute lung injury. Rats were exposed to 18 parts/ million NO2 for 12 h; control rats received filtered air for 12 h. In NO2-exposed rats, the total amount of rTI40 in bronchoalveolar fluid was elevated 2-fold compared with control values (P recoverable rTI40 can be used as an index of the severity of damage to the alveolar epithelium. PMID:9435578

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

    Van Ness, Michael; Jensen, Hanne; Adamson, Grete N; Kysar, Patricia E; Holland, Paul

    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....

  7. Lung pathology in case of acute radiation injury

    Results of pathomorphological studies of 27 patients exposed to total external γ- and β-radiation resulted from the Chernobyl accident and lost due to the acute radiation disease in the first weeks following radiation exposure are discussed. Dose range is 3.7-13.7 Gy. Two groups of pathological changes in lungs are revealed, those are: infection (bacterial, viral and fungous) ones caused by acute radiation disease and signs of respiratory distress-syndrome in adults

  8. A suspected case of transfusion-related acute lung injury

    Lulu Sherif; Srikantu, J.; Prithi Jain; Kishan Shetty; Brijesh Khandige

    2011-01-01

    Transfusion-related acute lung injury (TRALI) is a rare but serious complication of blood transfusion. We present a suspected case of TRALI in a 39-year-old female patient who underwent total abdominal hysterectomy under uneventful general anesthesia. The patient developed acute desaturation due to noncardiogenic pulmonary edema while receiving compatible blood transfusion on the second postoperative day. As her symptoms were refractory to supportive treatment, she was mechanically ventilated...

  9. Pattern Recognition Receptor–Dependent Mechanisms of Acute Lung Injury

    Xiang, Meng; Fan, Jie

    2009-01-01

    Acute lung injury (ALI) that clinically manifests as acute respiratory distress syndrome is caused by an uncontrolled systemic inflammatory response resulting from clinical events including sepsis, major surgery and trauma. Innate immunity activation plays a central role in the development of ALI. Innate immunity is activated through families of related pattern recognition receptors (PRRs), which recognize conserved microbial motifs or pathogen-associated molecular patterns (PAMPs). Toll-like...

  10. Diagnosis of Lung Cancer by Fractal Analysis of Damaged DNA

    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.

  11. Inhibition of the phospholipase A2 activity of peroxiredoxin 6 prevents lung damage with exposure to hyperoxia

    Bavneet Benipal

    2015-04-01

    Full Text Available Lung injury associated with hyperoxia reflects in part the secondary effects of pulmonary inflammation and the associated production of reactive oxygen species due to activation of NADPH oxidase, type 2 (NOX2. Activation of NOX2 requires the phospholipase A2 (PLA2 activity of peroxiredoxin 6 (Prdx6. Therefore, we evaluated whether blocking Prdx6 PLA2 activity using the inhibitor MJ33 would be protective in a mouse model of acute lung injury resulting from hyperoxic exposure. Mice were treated with an intraperitoneal injection of MJ33 (2.5 nmol/g body weight at the start of exposure (zero time and at 48 h during continuous exposure to 100% O2 for 80 h. Treatment with MJ33 reduced the number of neutrophils and the protein content in the fluid obtained by bronchoalveolar lavage, inhibited the increase in lipid peroxidation products in lung tissue, decreased the number of apoptotic cells in the lung, and decreased the perivascular edema associated with the 80 h exposure to hyperoxia. Thus, blocking Prdx6 PLA2 activity by MJ33 significantly protected lungs against damage from hyperoxia, presumably by preventing the activation of NOX2 and the amplification of lung injury associated with inflammation. These findings demonstrate that MJ33, a potent inhibitor of Prdx6 PLA2 activity, can protect mouse lungs against the manifestations of acute lung injury due to oxidative stress.

  12. Lipocalin-2 Test in Distinguishing Acute Lung Injury Cases from Septic Mice Without Acute Lung Injury

    Gao Zeng; Cong-wei Jia; Jie Liu; Shu-bin Guo

    2014-01-01

    Objective To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury (ALI) in mice. Methods Lipopolysaccharide (LPS, 10 mg/kg) injection or cecal ligation and puncture (CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups (n=10 in each group):group A (intraperitoneal LPS injection), group B (intravenous LPS injection via tail vein), group C (CLP with 25%of the cecum ligated), group D (CLP with 75%of the cecum ligated), and the control group (6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin (IL)-6 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves (ROC) and computing area under curve (AUC). Results In both group B and group D, most of the“main features”of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI (group A+group C), lipocalin-2 protein expression in septic mice with ALI (group B+group D) was significantly up-regulated in BALF (P Conclusions Lipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.

  13. Transfusion-related acute lung injury in multiple traumatized patients

    Alijanpour, Ebrahim; Jabbari, Ali; Hoseini, Fahimeh; Tabasi, Shabnam

    2012-01-01

    Background: Many of the multiple traumatized patients who refer to the hospital need transfusion. Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome associated with the transfusion of plasma-containing blood components. In the article, we present a case of TRALI following transfusion of packed red blood cells

  14. A case of acute fibrinous and organizing pneumonia during early postoperative period after lung transplantation.

    Alici, I O; Yekeler, E; Yazicioglu, A; Turan, S; Tezer-Tekce, Y; Demirag, F; Karaoglanoglu, N

    2015-04-01

    Acute fibrinous and organizing pneumonia (AFOP) is a distinct histologic pattern usually classified under the term chronic lung allograft dysfunction. We present a 48-year-old female patient who experienced AFOP during the 2nd week of double lung transplantation for pulmonary Langerhans cell histiocytosis and secondary pulmonary hypertension. During the 8th day after transplantation, fever and neutrophilia developed together with bilateral consolidation. Infection markers were elevated. Despite coverage of a full antimicrobial spectrum, the situation progressed. The patient was diagnosed with AFOP with transbronchial biopsy. The infiltration resolved and the patient improved dramatically with the initiation of pulse corticosteroid treatment. AFOP should be suspected when there is a pulmonary consolidation after lung transplantation, even in the very early post-transplantation period. Several causes, such as alveolar damage and drug reactions, should be considered in the differential diagnosis. PMID:25891742

  15. Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation

    An Jiang; Chang Liu; Feng Liu; Yu-Long Song; Quan-Yuan Li; Liang Yu; Yi Lv

    2012-01-01

    AIM: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation. METHODS: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4  °C for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion. ...

  16. Post-operative acute exacerbation of pulmonary fibrosis in lung cancer patients undergoing lung resection

    YANO, MOTOKI; Sasaki, Hidefumi; MORIYAMA, SATORU; HIKOSAKA, YU; YOKOTA, KEISUKE; Kobayashi, Susumu; HARA, MASAKI; Fujii, Yoshitaka

    2011-01-01

    Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) in lung cancer patients is a critical factor in post-operative mortality. The cause of AE development is unknown and AE may occur in patients without the diagnosis of IPF. We have conducted a retrospective study of consecutive patients who underwent lung cancer surgery since January 2004. Sixty-two patients with fibrous findings in preoperative high-resolution computed tomography were enrolled in the present study and clinicopatho...

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

    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.

  18. Transfusion-Related Acute Lung Injured (TRALI): Current Concepts.

    Álvarez, P; Carrasco, R; Romero-Dapueto, C; Castillo, R L

    2015-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated and no immune- mediated TRALI. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response, and lung vascular injury. Central clinical symptoms are dyspnea, tachypnea, tachycardia, cyanosis and pulmonary secretions, altogether with other hemodynamic alterations, such as hypotension and fever. Complementary to these clinical findings, long-term validated animal models for TRALI should allow the determination of the cellular targets for TRALI-inducing alloantibodies as well as delineation of the underlying pathogenic molecular mechanisms, and key molecular mediators of the pathology. Diagnostic criteria have been established and preventive measures have been implemented. These actions have contributed to the reduction in the overallnumber of fatalities. However, TRALI still remains a clinical problem. Any complication suspected of TRALI should immediately be reported. PMID:26312100

  19. Acute Aortic Dissection Extending Into the Lung.

    Makdisi, George; Said, Sameh M; Schaff, Hartzell V

    2015-07-01

    The radiologic manifestations of ruptured acute aortic dissection, Stanford type A aortic dissection, DeBakey type 1 can present in different radiographic scenarios with devastating outcomes. Here, we present a rare case of a 70-year-old man who presented to the emergency department with chest pain radiating to the back. A chest computed tomography scan showed a Stanford type A, DeBakey type 1, acute aortic dissection ruptured into the aortopulmonary window and stenosing the pulmonary trunk, both main pulmonary arteries, and dissecting the bronchovascular sheaths and flow into the pulmonary interstitium, causing pulmonary interstitial hemorrhage. The patient underwent emergent ascending aorta replacement with hemiarch replacement with circulatory arrest. The postoperative course was unremarkable. PMID:26140779

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

    Di Nardo Matteo; Perrotta Daniela; Stoppa Francesca; Cecchetti Corrado; Marano Marco; Pirozzi Nicola

    2008-01-01

    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 weig...

  1. Lung function evaluation in acute postradiation pneumonitis

    The aim of this study was pulmonary function evaluation in patients with radiation pneumonitis (rp). Study group included 18 patients with symptomatic rp (8 with breast cancer, 6 with Hodgkin's disease and 4 with lung cancer) treated at the Netherland s Cancer inst. In Amsterdam between 1988 and 1994. The lung function tests were performed at the time of rp presentation and monthly thereafter and consisted of a standard spirometry: forced expiratory volume in 1 sec. (FEV1), vital capacity (VC) and diffusing capacity for carbon monoxide (DLCO) performed with the use of a single breath technique. The mean values of DLCO, VC, FEV1 and TLC at the time of rp presentation were 72.2%, 91.0% and 85.8% of predicted value (pv), respectively. The results of the a bone tests at the last examination (66.4%, 85.6%, 77.2% and 76.2% of pv), respectively, were lower than those registered at the time of rp presentation. The highest degree of functional deterioration included diffusion capacity; the mean of the lowest values of DLCO was 56.4% of pv. Usually the lowest value of DLCO accompanied the exacerbation of clinical symptoms. The results of this study demonstrated pulmonary function deterioration in patients with rp. (author)

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

    Haji Altaf; Sharma Shekhar; Vijaykumar DK; Paul Jerry

    2008-01-01

    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...

  3. Role of Ventilation in Cases of Acute Respiratory Distress Syndrome /Acute Lung injury

    Hemant M Shah; Shilpa B Sutariya; Parul M Bhatt; Nishil Shah; Shweta Gamit

    2014-01-01

    Introduction: Acute lung injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are characterized by refractory hypoxemia that develops secondary to high-permeability pulmonary edema. These syndromes are gaining more attention as a means of better comprehending the pathophysiology of ARDS and possiblyfor modifying ventilatory management. In this context a study was done to compare role of invasive and non-invasive ventilation in cases of ARDS/ALI. Methods: in this study patients of AR...

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

    Ching-Hsia Hung; Jann-Inn Tzeng; Che-Ning Chang; Yu-Wen Chen; Chia-Ying Cho; Jhi-Joung Wang

    2013-01-01

    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 sedenta...

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

    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.

  6. Lung Surfactant Protein D (SP-D) Response and Regulation During Acute and Chronic Lung Injury

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F.;

    2013-01-01

    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......BACKGROUND: 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. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP-D in...

  7. Pros and cons of recruitment maneuvers in acute lung injury and acute respiratory distress syndrome.

    Rocco, Patricia R M; Pelosi, Paolo; de Abreu, Marcelo Gama

    2010-08-01

    In patients with acute lung injury and acute respiratory distress syndrome, a protective mechanical ventilation strategy characterized by low tidal volumes has been associated with reduced mortality. However, such a strategy may result in alveolar collapse, leading to cyclic opening and closing of atelectatic alveoli and distal airways. Thus, recruitment maneuvers (RMs) have been used to open up collapsed lungs, while adequate positive end-expiratory pressure (PEEP) levels may counteract alveolar derecruitment during low tidal volume ventilation, improving respiratory function and minimizing ventilator-associated lung injury. Nevertheless, considerable uncertainty remains regarding the appropriateness of RMs. The most commonly used RM is conventional sustained inflation, associated with respiratory and cardiovascular side effects, which may be minimized by newly proposed strategies: prolonged or incremental PEEP elevation; pressure-controlled ventilation with fixed PEEP and increased driving pressure; pressure-controlled ventilation applied with escalating PEEP and constant driving pressure; and long and slow increase in pressure. The efficiency of RMs may be affected by different factors, including the nature and extent of lung injury, capability of increasing inspiratory transpulmonary pressures, patient positioning and cardiac preload. Current evidence suggests that RMs can be used before setting PEEP, after ventilator circuit disconnection or as a rescue maneuver to overcome severe hypoxemia; however, their routine use does not seem to be justified at present. The development of new lung recruitment strategies that have fewer hemodynamic and biological effects on the lungs, as well as randomized clinical trials analyzing the impact of RMs on morbidity and mortality of acute lung injury/acute respiratory distress syndrome patients, are warranted. PMID:20658909

  8. The role of the endothelin system in experimental acute lung injury : With special reference to the formation of extra-vascular lung water

    Rossi, Patrik

    2006-01-01

    Acute lung injury is a major clinical challenge in the intensive care unit. Sepsis is the most frequent underlying cause of this pulmonary syndrome, which contains inflammation- induced diffuse alveolar damage and early stage high permeability edema. In spite of extensive research few therapies have reached the clinical arena, a fact that calls for additional interventional strategies. The role of the endothelin system in pulmonary disease has been established, and recen...

  9. Strategies to improve oxygenation in experimental acute lung injury

    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, including sepsis. shock, pneumonia. trauma, liquid aspiration. hematological disorders, smoke inhalation, and many others, In ARDS, the treatments available are still inadequate and morbidity, mort...

  10. Transfusion-Related Acute Lung Injury: The Work of DAMPs*

    Land, Walter G.

    2013-01-01

    Current notions in immunology hold that not only pathogen-mediated tissue injury but any injury activates the innate immune system. In principle, this evolutionarily highly conserved, rapid first-line defense system responds to pathogen-induced injury with the creation of infectious inflammation, and non-pathogen-induced tissue injury with ‘sterile’ tissue inflammation. In this review, evidence has been collected in support of the notion that the transfusion-related acute lung injury induces ...

  11. Transfusion-Related Acute Lung Injury Following Upper Extremity Replantation

    Celalettin Sever; Yalçın Külahçı; Cihan Şahin; Sinan Öksüz; Haluk Duman; Fuat Yüksel

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a common adverse effect of blood transfusion that is often underrecognised and underreported. We would like to report a case of TRALI after the replantation and transfusion of blood components in a male patient who had sustained a complete amputation of the right upper extremity. The level of amputation was just proximal to the humeral condyles. Replantation was performed 5 hours after the accident and 36 units of blood products were transfused...

  12. Transfusion-related acute lung injury: incidence and risk factors

    Toy, Pearl; Gajic, Ognjen; Bacchetti, Peter; Looney, Mark R.; Gropper, Michael A.; Hubmayr, Rolf; Lowell, Clifford A.; Norris, Philip J; Murphy, Edward L; Weiskopf, Richard B.; Wilson, Gregory; Koenigsberg, Monique; Lee, Deanna; Schuller, Randy; Wu, Ping

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current s...

  13. Transfusion-related acute lung injury; clinical perspectives.

    Kim, Jeongmin; Na, Sungwon

    2015-04-01

    Transfusion-related acute lung injury (TRALI) was introduced in 1983 to describe a clinical syndrome seen within 6 h of a plasma-containing blood products transfusion. TRALI is a rare transfusion complication; however, the FDA has suggested that TRALI is the leading cause of transfusion-related mortality. Understanding the pathogenesis of TRALI will facilitate adopting preventive strategies, such as deferring high plasma volume female product donors. This review outlines the clinical features, pathogenesis, treatment, and prevention of TRALI. PMID:25844126

  14. Transfusion-related acute lung injury; clinical perspectives

    Kim, Jeongmin; Na, Sungwon

    2015-01-01

    Transfusion-related acute lung injury (TRALI) was introduced in 1983 to describe a clinical syndrome seen within 6 h of a plasma-containing blood products transfusion. TRALI is a rare transfusion complication; however, the FDA has suggested that TRALI is the leading cause of transfusion-related mortality. Understanding the pathogenesis of TRALI will facilitate adopting preventive strategies, such as deferring high plasma volume female product donors. This review outlines the clinical features...

  15. Transfusion-related acute lung injury: Incidence and risk factors

    Toy, P; Gajic, O; Bacchetti, P; Looney, MR; Gropper, MA; Hubmayr, R; Lowell, CA; Norris, PJ; Murphy, EL; Weiskopf, RB; Wilson, G; Koenigsberg, M; Lee, D.; Schuller, R.; Wu, P.

    2011-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion- related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current ...

  16. Acute lung injury during antithymocyte globulin therapy for aplastic anemia

    Goligher, Ewan Christopher; Cserti-Gazdewich, Christine; Balter, Meyer; Gupta, Vikas; Joseph E Brandwein

    2009-01-01

    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-suppo...

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

    Jian WANG; 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 hematox...

  18. Bronchoalveolar Immunologic Profile of Acute Human Lung Transplant Allograft Rejection

    Gregson, Aric L.; Hoji, Aki; Saggar, Rajan; Ross, David J; Kubak, Bernard M; Jamieson, Beth D.; Weigt, S. Samuel; Lynch, Joseph P.; Ardehali, Abbas; Belperio, John A.; Yang, Otto O

    2008-01-01

    Bronchoalveolar lavage fluid (BALF) offers a potential means to diagnose acute rejection and could provide insight into the immune mechanisms responsible for lung allograft rejection. Transbronchial biopsies from 29 bronchoscopic procedures were assessed for rejection. Concurrent BALF lymphocyte subsets were examined by flow cytometry, including CD4+ and CD8+ T cells and their activation status via CD38 expression, NK, NK-like T (NT), B, T regulatory (Treg) and invariant receptor NK-T cells (...

  19. Acute lung injury induced by whole gastric fluid: hepatic acute phase response contributes to increase lung antiprotease protection

    Ayala, Pedro; Meneses, Manuel; Olmos, Pablo; Montalva, Rebeca; Droguett, Karla; Ríos, Mariana; Borzone, Gisella

    2016-01-01

    Background Gastric contents aspiration in humans is a risk factor for severe respiratory failure with elevated mortality. Although aspiration-induced local lung inflammation has been studied in animal models, little is known about extrapulmonary effects of aspiration. We investigated whether a single orotracheal instillation of whole gastric fluid elicits a liver acute phase response and if this response contributes to enrich the alveolar spaces with proteins having antiprotease activity. Met...

  20. [Pharmacological correction of toxic liver damage in patients with heavy forms of acute ethanol intoxication].

    Shikalova, I A; Shilov, V V; Vasil'ev, S A; Batotsyrenov, B V; Loladze, A T

    2012-01-01

    The efficiency of using remaxol and ademethionine in the therapy of patients with heavy acute alcohol intoxication on the background of toxic liver damage has been studied. The administration of remaxol led to improvement of the clinical treatment of alcohol intoxication, which is manifested by a decrease in the rate and duration of delirium tremens (from 33.9 to 10.8%), frequency of secondary lung disorders (from 18.5 to 3.1%), duration of stay in hospital (from 7.3 +/- 0.6 to 5.6 +/- 0.3 days), and total therapy duration (from 11.8 +/- 1.05 to 5.6 +/- 0.3 days). The results of biochemical investigations confirmed that remaxol and ademethionine provide effective treatment of the toxic liver damage. Remaxol decreases the degree of metabolic disorders to a greater extent than does ademethionine. PMID:22702109

  1. Gene 33/Mig6 inhibits hexavalent chromium-induced DNA damage and cell transformation in human lung epithelial cells

    Park, Soyoung; Li, Cen; Zhao, Hong; Darzynkiewicz, Zbigniew; Xu, Dazhong

    2016-01-01

    Hexavalent Chromium [Cr(VI)] compounds are human lung carcinogens and environmental/occupational hazards. The molecular mechanisms of Cr(VI) carcinogenesis appear to be complex and are poorly defined. In this study, we investigated the potential role of Gene 33 (ERRFI1, Mig6), a multifunctional adaptor protein, in Cr(VI)-mediated lung carcinogenesis. We show that the level of Gene 33 protein is suppressed by both acute and chronic Cr(VI) treatments in a dose- and time-dependent fashion in BEAS-2B lung epithelial cells. The inhibition also occurs in A549 lung bronchial carcinoma cells. Cr(VI) suppresses Gene 33 expression mainly through post-transcriptional mechanisms, although the mRNA level of gene 33 also tends to be lower upon Cr(VI) treatments. Cr(VI)-induced DNA damage appears primarily in the S phases of the cell cycle despite the high basal DNA damage signals at the G2M phase. Knockdown of Gene 33 with siRNA significantly elevates Cr(VI)-induced DNA damage in both BEAS-2B and A549 cells. Depletion of Gene 33 also promotes Cr(VI)-induced micronucleus (MN) formation and cell transformation in BEAS-2B cells. Our results reveal a novel function of Gene 33 in Cr(VI)-induced DNA damage and lung epithelial cell transformation. We propose that in addition to its role in the canonical EGFR signaling pathway and other signaling pathways, Gene 33 may also inhibit Cr(VI)-induced lung carcinogenesis by reducing DNA damage triggered by Cr(VI). PMID:26760771

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

    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

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

    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

  4. Lung sonography and recruitment in patients with early acute respiratory distress syndrome: A pilot study

    Stefanidis, Konstantinos; Dimopoulos, Stavros; Tripodaki, Elli-Sophia; Vitzilaios, Konstantinos; Politis, Panagiotis; Piperopoulos, Ploutarchos; Nanas, Serafim

    2011-01-01

    Introduction Bedside lung sonography is a useful imaging tool to assess lung aeration in critically ill patients. The purpose of this study was to evaluate the role of lung sonography in estimating the nonaerated area changes in the dependent lung regions during a positive end-expiratory pressure (PEEP) trial of patients with early acute respiratory distress syndrome (ARDS). Methods Ten patients (mean ± standard deviation (SD): age 64 ± 7 years, Acute Physiology and Chronic Health Evaluation ...

  5. Potential Effects of Medicinal Plants and Secondary Metabolites on Acute Lung Injury

    Daniely Cornélio Favarin

    2013-01-01

    Full Text Available Acute lung injury (ALI is a life-threatening syndrome that causes high morbidity and mortality worldwide. ALI is characterized by increased permeability of the alveolar-capillary membrane, edema, uncontrolled neutrophils migration to the lung, and diffuse alveolar damage, leading to acute hypoxemic respiratory failure. Although corticosteroids remain the mainstay of ALI treatment, they cause significant side effects. Agents of natural origin, such as medicinal plants and their secondary metabolites, mainly those with very few side effects, could be excellent alternatives for ALI treatment. Several studies, including our own, have demonstrated that plant extracts and/or secondary metabolites isolated from them reduce most ALI phenotypes in experimental animal models, including neutrophil recruitment to the lung, the production of pro-inflammatory cytokines and chemokines, edema, and vascular permeability. In this review, we summarized these studies and described the anti-inflammatory activity of various plant extracts, such as Ginkgo biloba and Punica granatum, and such secondary metabolites as epigallocatechin-3-gallate and ellagic acid. In addition, we highlight the medical potential of these extracts and plant-derived compounds for treating of ALI.

  6. Differential effects of kidney-lung cross-talk during acute kidney injury and bacterial pneumonia

    Singbartl, Kai; Bishop, Jeffery; Wen, Xiaoyan; Murugan, Raghavan; Chandra, Saurabh; Filippi, Marie-Dominique; John A Kellum

    2011-01-01

    Acute kidney injury (AKI) and acute lung injury (ALI) represent serious, complex clinical problems. The combination of AKI and ALI drastically decreases survival. However, detailed knowledge about the interactions between these two organs is scarce.

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

    Afshari, Arash; Brok, Jesper; Møller, Ann;

    2010-01-01

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

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

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

    2004-04-01

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

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

    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.)

  10. Epithelial cell apoptosis causes acute lung injury masquerading as emphysema.

    Mouded, Majd; Egea, Eduardo E; Brown, Matthew J; Hanlon, Shane M; Houghton, A McGarry; Tsai, Larry W; Ingenito, Edward P; Shapiro, Steven D

    2009-10-01

    Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement. Mice were treated with either intratracheal microcystin (MC) to induce apoptosis, intratracheal porcine pancreatic elastase (PPE), or their respective vehicles. Mice from all groups were inflated and morphometry was measured at various time points. Physiology measurements were performed for airway resistance, tissue elastance, and lung volumes. The groups were further analyzed by air-saline quasistatic measurements, surfactant staining, and surfactant functional studies. Mice treated with MC showed evidence of reversible airspace enlargement. In contrast, PPE-treated mice showed irreversible airspace enlargement. The airspace enlargement in MC-treated mice was associated with an increase in elastic recoil due to an increase in alveolar surface tension. PPE-treated mice showed a loss of lung elastic recoil and normal alveolar surface tension, a pattern more consistent with human emphysema. Airspace enlargement that occurs with the MC model of pulmonary epithelial cell apoptosis displays physiology distinct from human emphysema. Reversibility, restrictive physiology due to changes in surface tension, and alveolar enlargement associated with heterogeneous alveolar collapse are most consistent with a mild acute lung injury. Inflation near total lung capacity gives the appearance of enlarged alveoli as neighboring collapsed alveoli exert tethering forces. PMID:19188661

  11. Simkania negevensis and acute cellular rejection in lung transplant recipients.

    Jamal, Alainna J; Resende, Mariangela R; Prochnow, Taisa; McGilvray, Ian; Pilewski, Joseph M; Crespo, Maria M; Singer, Lianne G; McCurry, Kenneth R; Kolls, Jay K; Keshavjee, Shaf; Liles, W Conrad; Husain, Shahid

    2015-08-01

    Simkania negevensis infection has been hypothesized to play a role in lung transplant rejection. The incidence of S. negevensis infection and its association with acute cellular rejection (ACR) were determined in a prospective cohort study of 78 lung transplant recipients (LTRs) in Toronto, Canada, and Pittsburgh, USA, from July 2007 to January 2010. Simkania negevensis testing was detected by quantitative polymerase chain reaction (PCR) on bronchoalveolar lavage fluid. The relationship between S. negevensis and ACR was examined using Cox proportional hazards models and generalized linear and latent mixed models. Cumulative incidence estimates for time-to-ACR in S. negevensis PCR-positive vs. PCR-negative LTRs were 52.7% vs. 31.1% at six months and 68.9% vs. 44.6% at one yr, respectively. Although not statistically significant, there was a trend toward a higher risk of ACR among S. negevensis PCR-positive vs. PCR-negative LTRs in all statistical models. PMID:26009941

  12. Triptolide ameliorates lipopolysaccharide-induced acute lung injury in rats

    Gao, Jianling; Zhan, Ying; Chen, Jun; Wang, Lina; Yang, Jianping

    2013-01-01

    Background Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. In this study, the effects of triptolide on lipopolysaccharide (LPS)-induced ALI in rats were investigated. Methods Sixty-five male Sprague Dawley rats(approved by ethics committee of the First Affiliated Hospital of Soochow University) were randomly divided into five groups. The control group was injected with 2.5 mL saline/kg body weight via the tail vein and intraperitoneally with 1% dimethyl s...

  13. Brain damage after treatment for acute lymphoblastic leukemia

    In 34 patients treated for acute lymphoblastic leukemia (ALL), central nervous system (CNS) damage was assessed by clinical evaluation and brain magnetic resonance imaging (MRI). Twenty-seven of them had been off therapy from 5 to 109 months (median 64 months) while 7 had not completed the maintenance phase of their treatment. All the patients were disease-free when evaluated. None of the 3 patients who showed clinical CNS damage during the follow-up was symptomatic when submitted to MRI, while periventricular hyperintensity in T2-weighted images, suggestive of leukoencephalopathy, was present in 8 of the 34 patients. These subclinical abnormalities appear to be more frequent, transient in nature and treatment-related in patients evaluated shortly after the induction phase. Similar MRI findings seem, on the contrary, to be consequences of the disease on the CNS when appearing in long-term survivors. (orig.)

  14. A suspected case of transfusion-related acute lung injury

    Lulu Sherif

    2011-01-01

    Full Text Available Transfusion-related acute lung injury (TRALI is a rare but serious complication of blood transfusion. We present a suspected case of TRALI in a 39-year-old female patient who underwent total abdominal hysterectomy under uneventful general anesthesia. The patient developed acute desaturation due to noncardiogenic pulmonary edema while receiving compatible blood transfusion on the second postoperative day. As her symptoms were refractory to supportive treatment, she was mechanically ventilated for 3 days and successfully extubated on the fourth day. By exclusion, a clinical diagnosis of TRALI was made. The treatment for TRALI requires discontinuing transfusion and giving respiratory and cardiovascular support. Most cases show clinical improvement in first few hours and resolve completely within 96 h.

  15. Vascular and epithelial damage in the lung of the mouse after X rays or neutrons

    The response of the lung was studied in CFLP mice after exposure of the whole thorax to X rays (250 kVp) or cyclotron neutrons (16 MeV deuterons on Be, mean energy 7.5 MeV). To measure blood volume and leakage of plasma proteins, 51Cr-labeled red blood cells and 125I-albumin were injected intravenously and 24 h later lungs were lavaged via the trachea. Radioactivities in lung tissue and lavage fluid were determined to estimate the accumulation of albumin in the interstitial and alveolar spaces indicating damage to blood vessels and alveolar epithelium respectively. Function of type II pneumonocytes was assessed by the amounts of surfactant (assayed as lipid phosphorous) released into the lavage fluid. During the first 6 weeks, lavage protein and surfactant were increased, the neutron relative biological effectiveness (RBE) being unity. During pneumonitis at 12-24 weeks, surfactant levels were normal, blood volume was decreased, and both interstitial and alveolar albumin were increased. Albumin levels then decreased. At late times after exposure (42-64 weeks) alveolar albumin returned to normal but interstitial albumin was still slightly elevated. Values of RBE for changes in blood volume and interstitial and alveolar albumin at 15 weeks and for changes in blood volume and interstitial albumin at 46 weeks were 1.4, comparable with that for animal survival at 180 days. The results indicate that surfactant production is not critical for animal survival. They suggest that changes in blood vessels and alveolar epithelium occur during acute pneumonitis; epithelial repair follows but some vascular damage may persist. The time course of the changes in albumin levels did not correlate with increases in collagen biosynthesis which have been observed as early as 1 month after exposure and persist for up to 1 year

  16. Impact of mechanical ventilation on the pathophysiology of progressive acute lung injury.

    Nieman, Gary F; Gatto, Louis A; Habashi, Nader M

    2015-12-01

    The earliest description of what is now known as the acute respiratory distress syndrome (ARDS) was a highly lethal double pneumonia. Ashbaugh and colleagues (Ashbaugh DG, Bigelow DB, Petty TL, Levine BE Lancet 2: 319-323, 1967) correctly identified the disease as ARDS in 1967. Their initial study showing the positive effect of mechanical ventilation with positive end-expiratory pressure (PEEP) on ARDS mortality was dampened when it was discovered that improperly used mechanical ventilation can cause a secondary ventilator-induced lung injury (VILI), thereby greatly exacerbating ARDS mortality. This Synthesis Report will review the pathophysiology of ARDS and VILI from a mechanical stress-strain perspective. Although inflammation is also an important component of VILI pathology, it is secondary to the mechanical damage caused by excessive strain. The mechanical breath will be deconstructed to show that multiple parameters that comprise the breath-airway pressure, flows, volumes, and the duration during which they are applied to each breath-are critical to lung injury and protection. Specifically, the mechanisms by which a properly set mechanical breath can reduce the development of excessive fluid flux and pulmonary edema, which are a hallmark of ARDS pathology, are reviewed. Using our knowledge of how multiple parameters in the mechanical breath affect lung physiology, the optimal combination of pressures, volumes, flows, and durations that should offer maximum lung protection are postulated. PMID:26472873

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

    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

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

    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+ and cyclooxygenase-2+) and alternatively activated profibrotic (YM-1+ and galectin-3+) 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 lung injury induced by

  19. Hepatic damage during acute pancreatitis in the rat

    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

  20. Preemptive mechanical ventilation can block progressive acute lung injury.

    Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

    2016-02-01

    Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID:26855896

  1. Inhibition of SOCs Attenuates Acute Lung Injury Induced by Severe Acute Pancreatitis in Rats and PMVECs Injury Induced by Lipopolysaccharide.

    Wang, Guanyu; Zhang, Jingwen; Xu, Caiming; Han, Xiao; Gao, Yanyan; Chen, Hailong

    2016-06-01

    Acute lung injury (ALI) is a critical complication of the severe acute pancreatitis (SAP), characterized by increased pulmonary permeability with high mortality. Pulmonary microvascular endothelial cells (PMVECs) injury and apoptosis play a key role in ALI. Previous studies indicated that store-operated calcium entry (SOCE) could regulate a variety of cellular processes. The present study was to investigate the effects of SOCE inhibition on ALI induced by SAP in Sprague-Dawley rats, and PMVECs injury induced by lipopolysaccharide (LPS). Rat model of SAP-associated ALI were established by the retrograde infusion of sodium deoxycholate. Serum levels of amylase, TNF-α, and IL-6, histological changes, water content of the lung, oxygenation index, and ultrastructural changes of PMVECs were examined in ALI rats with or without store-operated Ca(2+) channels (SOCs) pharmacological inhibitor (2-aminoethoxydiphenyl borate, 2-APB) pretreatment. For in vitro studies, PMVECs were transiently transfected with or without small interfering RNA (siRNA) against calcium release-activated calcium channel protein1 (Orai1) and stromal interaction molecule1 (STIM1), the two main molecular constituents of SOCs, then exposed to LPS. The viability of PMVECs was determined. The expression of STIM1, Orai1, Bax, and caspase3, both in lung tissue and in PMVECs, were assessed by quantitative real-time PCR and western blot. Administration of sodium deoxycholate upregulated the expression of SOCs proteins in lung tissue. Similarly, the SOCs proteins were increased in PMVECs induced by LPS. 2-APB reduced the serum levels of amylase, TNF-α, and IL-6, and attenuated lung water content and histological findings. In addition, the decreased oxygenation index and ultrastructural damage in PMVECs associated with SAP were ameliorated after administration of 2-APB. Knockdown of STIM1 and Orai1 inhibited LPS-induced PMVECs death. Furthermore, blockade of SOCE significantly suppressed Orai1, STIM1, Bax

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

    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.

  3. [Role of computed tomography in the diagnosis of acute lung injury/acute respiratory distress syndrome].

    Mazzei, Maria Antonietta; Guerrini, Susanna; Cioffi Squitieri, Nevada; Franchi, Federico; Volterrani, Luca; Genovese, Eugenio Annibale; Macarini, Luca

    2012-11-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a complex pulmonary pathology with high mortality rates, manifesting over a wide range of severity. Clinical diagnosis relies on the following 4 criteria stated by the American-European Consensus Conference: acute onset of impaired gas exchange, severe hypoxemia defined as a PaO2 to FiO2 ratio <300 (PaO2 in mmHg), bilateral diffuse infiltration on chest X-ray; pulmonary artery wedge pressure of ≤18 mmHg to rule out cardiogenic causes of pulmonary edema. The aim of this study was to determine the usefulness of CT in the diagnosis and management of this condition. PMID:23096732

  4. Matrix Metalloproteinase Activity in Pediatric Acute Lung Injury

    Michele YF Kong, Amit Gaggar, Yao Li, Margaret Winkler, J Edwin Blalock, JP Clancy

    2009-01-01

    Full Text Available Pediatric Acute Lung Injury (ALI is associated with a high mortality and morbidity, and dysregulation of matrix metalloproteinases (MMPs may play an important role in the pathogenesis and evolution of ALI. Here we examined MMP expression and activity in pediatric ALI compared with controls. MMP-8, -9, and to a lesser extent, MMP-2, -3, -11 and -12 were identified at higher levels in lung secretions of pediatric ALI patients compared with controls. Tissue Inhibitor of Matrix metalloproteinase-1 (TIMP-1, a natural inhibitor of MMPs was detected in most ALI samples, but MMP-9:TIMP-1 ratios were high relative to controls. In subjects who remained intubated for ≥10 days, MMP-9 activity decreased, with > 80% found in the latent form. In contrast, almost all MMP-8 detected at later disease course was constitutively active. Discriminating MMP-9:TIMP-1 ratios were found in those who had a prolonged ALI course. These results identify a specific repertoire of MMP isoforms in the lung secretions of pediatric ALI patients, and demonstrate inverse changes in MMPs -8 and -9 with protracted disease.

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

    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. PMID:25008149

  6. Metabolomics and Its Application to Acute Lung Diseases.

    Stringer, Kathleen A; McKay, Ryan T; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a "snapshot" in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision-making and

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

    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.

  8. Metastasis-Induced Acute Pancreatitis in a Patient with Small Cell Carcinoma of the Lungs

    Hajime Tanaka

    2009-09-01

    Full Text Available Context Pancreatic metastases are relatively common in advanced lung cancers (both small cell lung carcinoma and non-small cell lung carcinoma, but metastasis-induced acute pancreatitis is very unusual. Case report A 51-year-old woman with small cell carcinoma of the lung developed acute pancreatitis as the initial manifestation. Abdominal ultrasonography revealed multiple pancreatic metastases which were confirmed by magnetic resonance imaging. Conventional treatment did not improve her condition. However, aggressive chemotherapy resulted in a dramatic recovery from the acute pancreatitis and significant improvement in her general condition. Conclusion When cases of acute pancreatitis in patients with small cell lung carcinoma are encountered, we must consider the possibility of metastasis-induced acute pancreatitis and that, should pancreatic metastases be found in these patients, chemotherapy may provide substantial benefit.

  9. Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury

    M. Corbel

    2000-07-01

    Full Text Available Acute lung injury is characterized by a severe disruption of alveolo-capillary structures and includes a variety of changes in lung cell populations. Evidence suggests the occurrence of rupture of the basement membranes and interstitial matrix remodeling during acute lung injury. The dynamic equilibrium of the extracellular matrix (ECM under physiological conditions is a consequence of the balance between the regulation of synthesis and degradation of ECM components. Matrix metalloproteinases (MMPs represent a group of enzymes involved in the degradation of most of the components of the ECM and therefore participate in tissue remodeling associated with pathological situations such as acute lung injury. MMP activity is regulated by proteolytic activation of the latent secreted proenzyme and by interaction with specific tissue inhibitors of metalloproteinases. This review details our knowledge of the involvement of MMPs, namely MMP-2 and MMP-9, in acute lung injury and acute respiratory distress syndrome.

  10. Short women with severe sepsis-related acute lung injury receive lung protective ventilation less frequently: an observational cohort study

    Han, SeungHye; Martin, Greg S.; Maloney, James P.; Shanholtz, Carl; Barnes, Kathleen C.; Murray, Stacey; Sevransky, Jonathan E.

    2011-01-01

    Introduction Lung protective ventilation (LPV) has been shown to improve survival and the duration of mechanical ventilation in acute lung injury (ALI) patients. Mortality of ALI may vary by gender, which could result from treatment variability. Whether gender is associated with the use of LPV is not known. Methods A total of 421 severe sepsis-related ALI subjects in the Consortium to Evaluate Lung Edema Genetics from seven teaching hospitals between 2002 and 2008 were included in our study. ...

  11. Clinical review: The implications of experimental and clinical studies of recruitment maneuvers in acute lung injury

    Piacentini Gómez, Enrique; Villagrá, Ana; López Aguilar, Josefina; Blanch Torra, Lluís

    2003-01-01

    Mechanical ventilation can cause and perpetuate lung injury if alveolar overdistension, cyclic collapse, and reopening of alveolar units occur. The use of low tidal volume and limited airway pressure has improved survival in patients with acute lung injury or acute respiratory distress syndrome. The use of recruitment maneuvers has been proposed as an adjunct to mechanical ventilation to re-expand collapsed lung tissue. Many investigators have studied the benefits of recruitment maneuvers in ...

  12. Neutrophil Elastase Contributes to Acute Lung Injury Induced by Bilateral Nephrectomy

    Ishii, Tomoko; DOI, Kent; Okamoto, Koji; Imamura, Mitsuru; Dohi, Makoto; Yamamoto, Kazuhiko; Fujita, Toshiro; Noiri, Eisei

    2010-01-01

    Acute kidney injury (AKI) is a serious problem in critically ill patients of intensive care units. It has been reported previously that AKI can induce acute lung injury (ALI), as well as cause injuries to other remote organs, including the lungs. Patients with AKI complicated by ALI show remarkably high mortality. ALI is characterized by neutrophil infiltration into the lung. Neutrophil elastase (NE) is a key enzyme for tissue injury caused by activated neutrophils, such as occurs in ALI. The...

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

    Luh, Shi-Ping; Chiang, Chi-huei

    2006-01-01

    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/AR...

  14. Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury.

    Shaver, Ciara M; Grove, Brandon S; Clune, Jennifer K; Mackman, Nigel; Ware, Lorraine B; Bastarache, Julie A

    2016-01-01

    Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF(∆mye), LysM.Cre(+/-)TF(flox/flox)) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI. PMID:26924425

  15. Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury.

    Wu, Deqing; Zeng, Yue; Fan, Yuting; Wu, Jianghong; Mulatibieke, Tunike; Ni, Jianbo; Yu, Ge; Wan, Rong; Wang, Xingpeng; Hu, Guoyong

    2016-01-01

    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. PMID:26841848

  16. Metastasis-induced acute pancreatitis in a patient with small cell carcinoma of the lung.

    Kim, K. H.; Kim, C D; Lee, S. J.; Lee, G.; Jeen, Y T; Lee, H.S.; Chun, H J; Song, C. W.; Um, S. H.; Lee, S. W.; Choi, J. H.; Ryu, H. S.; Hyun, J. H.

    1999-01-01

    Acute pancreatitis in cancer patients can be secondary to the malignant process itself or a complication of antineoplastic agent administration. However, acute pancreatitis caused by metastatic carcinoma of the pancreas is an uncommon condition with a poor prognosis. We report a case of a 63-year-old man with small cell carcinoma of the lung, who developed acute pancreatitis lately. Thirteen months earlier, he developed small cell carcinoma of the lung and received 6 cycles of chemotherapy. A...

  17. Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats.

    Lin, Hen I; Chu, Shi Jye; Hsu, Kang; Wang, David

    2004-01-01

    In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. Pretreatment with inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the parameters reflective of lung injury increased significantly except PAP (P<0.05). Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM) attenuated the detrimental effect of inhaled NO in PMA-induced lung injury, except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO. PMID:14643171

  18. The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.

    Grabiec, Aleksander M; Hussell, Tracy

    2016-07-01

    Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called 'efferocytosis'. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections. PMID:26957481

  19. Transfusion-Related Acute Lung Injury Following Upper Extremity Replantation

    Celalettin Sever

    2012-09-01

    Full Text Available Transfusion-related acute lung injury (TRALI is a common adverse effect of blood transfusion that is often underrecognised and underreported. We would like to report a case of TRALI after the replantation and transfusion of blood components in a male patient who had sustained a complete amputation of the right upper extremity. The level of amputation was just proximal to the humeral condyles. Replantation was performed 5 hours after the accident and 36 units of blood products were transfused intraoperatively. Subsequently, during the early postoperative period, TRALI was revealed. In this case report, the circumstances of this injury and preventive measures are discussed to understand and recognise this condition in order to reduce the morbidity and mortality of TRALI. It is important to distinguish TRALI from other causes of pulmonary oedema because early diagnosis and management are associated with a favourable outcome.

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

    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.

  1. Titrating Open Lung PEEP in Acute Lung Injury : A clinical method based on changes in dynamic compliance

    Suarez Sipmann, Fernando

    2008-01-01

    The recognition that supportive mechanical ventilation can also damage the lung, the so called ventilation induced lung injury (VILI), has revived the more than 40 year long debate on the optimal level of PEEP to be used. It is established that the prevention of VILI improves patient outcome and that PEEP exerts protective effects by preventing unstable diseased alveoli from collapsing. Therefore, the term “open lung PEEP” (OL-PEEP) has been introduced as the end-expiratory pressure that keep...

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

    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

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

    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 fur...

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

    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, in...... endonuclease III and fapyguanine glycosylase (FPG) sensitive sites increased at the intermediate dose levels. The induction of DNA damage by DEP exposure did not increase the expression of the repair genes OGG1 and ERCC1 at the mRNA level. The present study indicates that the lung is a target organ for primary...... DNA damage following oral exposure to DEP. DNA damage was induced following exposure to relatively low levels of DEP, but under the conditions used in the present experiment DNA damage did not result in an increased mutation rate....

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

    Müller, Anne Kirstine; Farombi, E.O.; Møller, P.; Autrup, H.N.; Vogel, U.; Wallin, H.; Dragsted, Lars Ove; Loft, S.; Binderup, Mona-Lise

    . 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, in...... endonuclease III and fapyguanine glycosylase (FPG) sensitive sites increased at the intermediate dose levels. The induction of DNA damage by DEP exposure did not increase the expression of the repair genes OGG1 and ERCC1 at the mRNA level. The present study indicates that the lung is a target organ for primary...... DNA damage following oral exposure to DEP. DNA damage was induced following exposure to relatively low levels of DEP, but under the conditions used in the present experiment DNA damage did not result in an increased mutation rate....

  6. [Continuously alternating prone and supine positioning in acute lung failure].

    Walz, M; Muhr, G

    1992-11-01

    Acute respiratory failure is still one the main problems in surgical intensive care. Unknown pathophysiological mechanisms permit only symptomatic therapy. Today ventilatory strategies by using PEEP und IRV are established to improve gas exchange and FRC by recruiting collapsed alveoli, decreasing intrapulmonary shunting and returning V/Q matching to normal. Furthermore different studies have shown the effects of supine and lateral decubitus posture in patients with acute respiratory failure. There are only rare reports on using the prone position, which doesn't require two-lung ventilation in difference to lateral position. We have studied 16 patients with acute respiratory failure by using continuous changing between prone and supine position under mechanical ventilation. All were male, aged 41.3 years in the middle and showed an average "Injury Severity Score" of 30 (13-50). 15 were trauma patients with blunt chest trauma in 11 cases. We have used prone position on threatening or manifest ARDS. In all patients we observed an increment of PaO2 during prone position on to 48 mmHg so that FiO2 could be reduced on an average of 0.2 within the first 48 h since changing patient's position. Posture changing depends on blood gas analysis, specifically on decreasing PaO2 after previous increment. Patients remained in prone and supine position at a mean of 6.3 (4.5-20) h and posture changing was proceeded over a period of 15.4 (7-32) days. No problems recording to blood pressure or mechanical ventilation appeared during prone position. 11 of 16 patients survived (68.8%), 5 died of cardiac (2) and multi organic failure (3) in connection with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1458988

  7. Effects of resolvin D1 on inflammatory responses and oxidative stress of lipopolysaccharide-induced acute lung injury in mice

    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

  8. Acute pancreatitis in association with small cell lung carcinoma: potential pitfall in diagnosis and management.

    Allan, S. G.; Bundred, N; Eremin, O; Leonard, R. C.

    1985-01-01

    Tumour metastases to the pancreas are a rare but recognized cause of acute pancreatitis, there is a 24-40% incidence of pancreatic involvement from small cell lung cancer in autopsy series but only a very few cases of tumour-induced acute pancreatitis have been described. Chemotherapy has been advocated as the primary therapy in patients with known oat cell carcinoma who develop acute pancreatitis. We describe 2 patients with acute haemorrhagic pancreatitis in association with disseminated sm...

  9. Stem cells--potential for repairing damaged lungs and growing human lungs for transplant.

    Bishop, Anne E; Rippon, Helen J

    2006-08-01

    Repair or regeneration of defective lung epithelium would be of great therapeutic potential. It is estimated by the British Lung Foundation that 1 in 7 people in the UK is affected by a lung disease and that 1 in 4 admissions to children's wards are as a result of respiratory problems. Potential cellular sources for the regeneration of lung tissue in vivo or lung tissue engineering in vitro include endogenous pulmonary epithelial stem cells, extrapulmonary circulating stem cells and embryonic stem cells. This article discusses the potential role of each of these stem cell types in future approaches to the treatment of lung injury and disease. PMID:16856797

  10. Transfusion-related Acute Lung Injury in the Critically Ill: Prospective Nested Case-Control Study

    Gajic, Ognjen; Rana, Rimki; Winters, Jeffrey L.; Yilmaz, Murat; Mendez, Jose L.; Rickman, Otis B.; O'Byrne, Megan M.; Evenson, Laura K; Malinchoc, Michael; DeGoey, Steven R.; Afessa, Bekele; Hubmayr, Rolf D.; Moore, S. Breanndan

    2007-01-01

    Rationale: Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies.

  11. Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice

    Qiao, Ying-Ying; Liu, Xiao-Qin; Xu, Chang-Qin; Zhang, Zheng; Xu, Hong-wei

    2016-01-01

    AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved.

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

    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.

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

    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

  14. Treatment of acute lung injury by targeting MG53-mediated cell membrane repair

    Jia, Yanlin; Chen, Ken; Lin, Peihui; Lieber, Gissela; Nishi, Miyuki; Yan, Rosalie; Wang, Zhen; Yao, Yonggang; LI Yu; Bryan A Whitson; Duann, Pu; Li, Haichang; Zhou, Xinyu; Zhu, Hua; Takeshima, Hiroshi

    2014-01-01

    Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. Mice lacking MG53 show increased susceptibility to ischemia-reperfusion and over-ventilation induced injury to the lung when compared with wild type mice. Extracellula...

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

    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.

  16. Prospective study on the clinical course and outcomes in transfusion-related acute lung injury

    Looney, MR; Roubinian, N; Gajic, O; Gropper, MA; Hubmayr, RD; Lowell, CA; Bacchetti, P.; Wilson, G.; Koenigsberg, M; Lee, DC; Wu, P; Grimes, B; Norris, PJ; Murphy, EL; Gandhi, MJ

    2014-01-01

    OBJECTIVE:: Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. A prospective study using electronic surveillance was conducted at two academic medical centers in the United States with the objective to define the clinical course and outcomes in transfusion-related acute lung injury cases. DESIGN:: Prospective case study with controls. SETTING:: University of California, San Francisco and Mayo Clinic, Rochester. PATIENTS:: We prospectively enrolled 89 ...

  17. Fatal transfusion related acute lung injury following coronary artery by-pass surgery: a case report

    Bawany, Fauzia Ahmad; Sharif, Hasanat

    2008-01-01

    Background Transfusion related acute lung injury (TRALI) is a potentially fatal Acute Lung Injury following transfusion of blood components. Hypotheses implicate donor-derived anti-human leukocyte antigen or granulocyte antibodies reacting with recipients' leukocytes, releasing inflammatory mediators. Lack of agreement on underlying cellular and molecular mechanisms renders improving transfusion safety difficult and expensive. Case Presentation Literature search has not revealed any case of T...

  18. KL-6 in acute lung injury: will it leave its mark?

    Shyamsundar, Murali; Danny F McAuley

    2008-01-01

    Studies have indicated that measuring biochemical measures of epithelial injury in plasma and alveolar fluid may be useful in predicting outcome in acute lung injury. The present commentary briefly reviews the evidence supporting the use of these biochemical biomarkers of epithelial injury in acute lung injury, and in particular KL-6, as well as their limitations. The article additionally proposes the need for physiological markers of epithelial function to complement current biochemical biom...

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

    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...

  20. Ventilation-perfusion scan in the acutely ill patient with unilateral hyperlucent lung

    A patient with a unilateral hyperlucent lung with acute respiratory complaints is presented. A ventilation-perfusion scan was performed to rule out pulmonary embolism. The perfusion scan ( [/sup 99m/TC]MAA) showed peripheral perfusion defects in the hyperlucent lung. The ventilation study (133Xe) demonstrated peripheral ventilatory defects on the single breath image in the hyperlucent lung, the filling in of these on the equilibrium view, and diffusely delayed washout in the affected lung. These findings were suggestive of the Swyer-James syndrome and critical in excluding the numerous other causes of unilateral hyperlucent lung, which are discussed. The importance of the ventilation-perfusion study (and particularly the ventilation scan) in the patient with unilateral hyperlucent lung and acute respiratory symptoms is stressed. In addition, a discussion of the Swyer-James syndrome is included

  1. A case of lung cancer associated with acute respiratory distress syndrome after thoracic radiotherapy

    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)

  2. Transfusion related acute lung injury in a perinatal woman

    Deepthi Krishna G

    2016-01-01

    Full Text Available We report the case of a 26-year-old female who underwent emergency caesarean section at a private hospital and was referred to the Government Maternity Hospital (GMH, Tiruapti for bleeding per vaginum 4 hours after delivery. She had received one unit of whole blood transfusion outside. Later, whole blood, platelets (n= 1 unit and fresh frozen plasma (n= 2 units were transfused over a period of 6 hours at GMH, Tirupati. Two hours there after, she complained of sudden breathlessness with cough. On examination, bilateral basal crepitations and wheezing were noted. Fall in oxygen saturation by pulse oximetry, hypotension, tachypnoea and mild fever were also noted. Chest radiograph showed bilateral frontal opacities. Possibility of transfusion-related acute lung injury (TRALI was considered. Supportive treatment included supplemental oxygen through oxygen mask followed by assisted mechanical ventilation and the patient improved. The present case highlights the importance of transfusion related adverse events so as to facilitate prompt recognition and appropriate treatment at the right time.

  3. Time-dependent changes of autophagy and apoptosis in lipopolysaccharide-induced rat acute lung injury

    Li Lin; Lijun Zhang; Liangzhu Yu; Lu Han; Wanli Ji; Hui Shen; Zhenwu Hu

    2016-01-01

    Objective(s): Abnormal lung cell death including autophagy and apoptosis is the central feature in acute lung injury (ALI). To identify the cellular mechanisms and the chronology by which different types of lung cell death are activated during lipopolysaccharide (LPS)-induced ALI, we decided to evaluate autophagy (by LC3-II and autophagosome) and apoptosis (by caspase-3) at different time points after LPS treatment in a rat model of LPS-induced ALI. Materials and Methods: Sprague-Dawley ra...

  4. Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis

    Lange, Matthias; Szabo, Csaba; Traber, Daniel L.; Horvath, Eszter; Hamahata, Atsumori; Nakano, Yoshimitsu; Traber, Lillian D.; Cox, Robert A.; Schmalstieg, Frank C.; Herndon, David N.; Enkhbaatar, Perenlei

    2012-01-01

    The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure following acute lung injury (ALI) and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation injury and instillation of live Pseudomonas aeruginosa into both lungs. The sheep and were euthanized at 4, 8, 12, 18, and 24 hours p...

  5. Leaky lysosomes in lung transplant macrophages: azithromycin prevents oxidative damage

    Persson H L

    2012-09-01

    Full Text Available Abstract Background Lung allografts contain large amounts of iron (Fe, which inside lung macrophages may promote oxidative lysosomal membrane permeabilization (LMP, cell death and inflammation. The macrolide antibiotic azithromycin (AZM accumulates 1000-fold inside the acidic lysosomes and may interfere with the lysosomal pool of Fe. Objective Oxidative lysosomal leakage was assessed in lung macrophages from lung transplant recipients without or with AZM treatment and from healthy subjects. The efficiency of AZM to protect lysosomes and cells against oxidants was further assessed employing murine J774 macrophages. Methods Macrophages harvested from 8 transplant recipients (5 without and 3 with ongoing AZM treatment and 7 healthy subjects, and J774 cells pre-treated with AZM, a high-molecular-weight derivative of the Fe chelator desferrioxamine or ammonium chloride were oxidatively stressed. LMP, cell death, Fe, reduced glutathione (GSH and H-ferritin were assessed. Results Oxidant challenged macrophages from transplants recipients without AZM exhibited significantly more LMP and cell death than macrophages from healthy subjects. Those macrophages contained significantly more Fe, while GSH and H-ferritin did not differ significantly. Although macrophages from transplant recipients treated with AZM contained both significantly more Fe and less GSH, which would sensitize cells to oxidants, these macrophages resisted oxidant challenge well. The preventive effect of AZM on oxidative LMP and J774 cell death was 60 to 300 times greater than the other drugs tested. Conclusions AZM makes lung transplant macrophages and their lysososomes more resistant to oxidant challenge. Possibly, prevention of obliterative bronchiolitis in lung transplants by AZM is partly due to this action.

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

    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.

  7. Regulation of alveolar procoagulant activity and permeability in direct acute lung injury by lung epithelial tissue factor.

    Shaver, Ciara M; Grove, Brandon S; Putz, Nathan D; Clune, Jennifer K; Lawson, William E; Carnahan, Robert H; Mackman, Nigel; Ware, Lorraine B; Bastarache, Julie A

    2015-11-01

    Tissue factor (TF) initiates the extrinsic coagulation cascade in response to tissue injury, leading to local fibrin deposition. Low levels of TF in mice are associated with increased severity of acute lung injury (ALI) after intratracheal LPS administration. However, the cellular sources of the TF required for protection from LPS-induced ALI remain unknown. In the current study, transgenic mice with cell-specific deletions of TF in the lung epithelium or myeloid cells were treated with intratracheal LPS to determine the cellular sources of TF important in direct ALI. Cell-specific deletion of TF in the lung epithelium reduced total lung TF expression to 39% of wild-type (WT) levels at baseline and to 29% of WT levels after intratracheal LPS. In contrast, there was no reduction of TF with myeloid cell TF deletion. Mice lacking myeloid cell TF did not differ from WT mice in coagulation, inflammation, permeability, or hemorrhage. However, mice lacking lung epithelial TF had increased tissue injury, impaired activation of coagulation in the airspace, disrupted alveolar permeability, and increased alveolar hemorrhage after intratracheal LPS. Deletion of epithelial TF did not affect alveolar permeability in an indirect model of ALI caused by systemic LPS infusion. These studies demonstrate that the lung epithelium is the primary source of TF in the lung, contributing 60-70% of total lung TF, and that lung epithelial, but not myeloid, TF may be protective in direct ALI. PMID:25884207

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

    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-up study, the

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

    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

  10. C-reactive protein enhances murine antibody-mediated transfusion-related acute lung injury.

    Kapur, Rick; Kim, Michael; Shanmugabhavananthan, Shanjeevan; Liu, Jonathan; Li, Yuan; Semple, John W

    2015-12-17

    Transfusion-related acute lung injury (TRALI) is a syndrome of respiratory distress triggered by blood transfusions and is the leading cause of transfusion-related mortality. TRALI has primarily been attributed to passive infusion of HLA and/or human neutrophil antigen antibodies present in transfused blood products, and predisposing factors such as inflammation are known to be important for TRALI initiation. Because the acute-phase protein C-reactive protein (CRP) is highly upregulated during infections and inflammation and can also enhance antibody-mediated responses such as in vitro phagocytosis, respiratory burst, and in vivo thrombocytopenia, we investigated whether CRP affects murine antibody-mediated TRALI induced by the anti-major histocompatibility complex antibody 34-1-2s. We found that BALB/c mice injected with 34-1-2s or CRP alone were resistant to TRALI, however mice injected with 34-1-2s together with CRP had significantly enhanced lung damage and pulmonary edema. Mechanistically, 34-1-2s injection with CRP resulted in a significant synergistic increase in plasma levels of the neutrophil chemoattractant macrophage inflammatory protein-2 (MIP-2) and pulmonary neutrophil accumulation. Importantly, murine MIP-2 is the functional homolog of human interleukin-8, a known risk factor for human TRALI. These results suggest that elevated in vivo CRP levels, like those observed during infections, may significantly predispose recipients to antibody-mediated TRALI reactions and support the notion that modulating CRP levels is an effective therapeutic strategy to reduce TRALI severity. PMID:26453659

  11. The Design of Future Pediatric Mechanical Ventilation Trials for Acute Lung Injury

    Robinder G Khemani; Newth, Christopher J.L.

    2010-01-01

    Pediatric practitioners face unique challenges when attempting to translate or adapt adult-derived evidence regarding ventilation practices for acute lung injury or acute respiratory distress syndrome into pediatric practice. Fortunately or unfortunately, there appears to be selective adoption of adult practices for pediatric mechanical ventilation, many of which pose considerable challenges or uncertainty when translated to pediatrics. These differences, combined with heterogeneous managemen...

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

    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.

  13. A case of transfusion-related acute lung injury induced by anti-human leukocyte antigen antibodies in acute leukemia

    Jin, Sun Mi; Jang, Moon Ju; Huh, Ji Young; Park, Myoung Hee; Song, Eun Young; Oh, Doyeun

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patient...

  14. Spred-2 Deficiency Exacerbates Lipopolysaccharide-Induced Acute Lung Inflammation in Mice

    Yang Xu; Toshihiro Ito; Soichiro Fushimi; Sakuma Takahashi; Junya Itakura; Ryojiro Kimura; Miwa Sato; Megumi Mino; Akihiko Yoshimura; Akihiro Matsukawa

    2014-01-01

    BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe and life-threatening acute lung injury (ALI) that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK) pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spr...

  15. Ventilator-Induced Lung Injury (VILI) in Acute Respiratory Distress Syndrome (ARDS): Volutrauma and Molecular Effects

    Carrasco Loza, R; Villamizar Rodríguez, G; Medel Fernández, N

    2015-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a clinical condition secondary to a variety of insults leading to a severe acute respiratory failure and high mortality in critically ill patients. Patients with ARDS generally require mechanical ventilation, which is another important factor that may increase the ALI (acute lung injury) by a series of pathophysiological mechanisms, whose common element is the initial volutrauma in the alveolar units, and forming part of an entity known clinically...

  16. Suspected Transfusion Related Acute Lung Injury Improving following Administration of Tranexamic Acid: A Case Report

    Stan Ryniak; Piotr Harbut; Anders Östlund; Andrzej Mysiak; Jan G. Jakobsson

    2014-01-01

    A 16-year-old woman with craniofacial injury developed severe acute respiratory failure under the primary reconstructive surgical procedure requiring several units of blood and plasma. A transfusion related acute lung injury (TRALI) was suspected and supportive treatment was initiated. Because of the severity of symptoms, acute extracorporeal membrane oxygenation (ECMO) was planned. During preparation for ECMO, a single intravenous dose, 1 g of tranexamic acid, was administered and a remarkab...

  17. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs* **

    Torres, Ronaldo Lopes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Ferreira, Maria Beatriz Cardoso; Cardoso, Paulo Francisco Guerreiro; Belló-Klein, Adriane

    2014-01-01

    Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methy...

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

    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

  19. MicroRNA Regulation of Acute Lung Injury and Acute Respiratory Distress Syndrome.

    Rajasekaran, Subbiah; Pattarayan, Dhamotharan; Rajaguru, P; Sudhakar Gandhi, P S; Thimmulappa, Rajesh K

    2016-10-01

    The acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), is a very common condition associated with critically ill patients, which causes substantial morbidity and mortality worldwide. Despite decades of research, effective therapeutic strategies for clinical ALI/ARDS are not available. In recent years, microRNAs (miRNAs), small non-coding molecules have emerged as a major area of biomedical research as they post-transcriptionally regulate gene expression in diverse biological and pathological processes, including ALI/ARDS. In this context, this present review summarizes a large body of evidence implicating miRNAs and their target molecules in ALI/ARDS originating largely from studies using animal and cell culture model systems of ALI/ARDS. We have also focused on the involvement of miRNAs in macrophage polarization, which play a critical role in regulating the pathogenesis of ALI/ARDS. Finally, the possible future directions that might lead to novel therapeutic strategies for the treatment of ALI/ARDS are also reviewed. J. Cell. Physiol. 231: 2097-2106, 2016. © 2016 Wiley Periodicals, Inc. PMID:26790856

  20. [Postural therapy during mechanical pulmonary ventilation with PEEP in patients with unilateral lung damage].

    Neverin, V K; Vlasenko, A V; Mitrokhin, A A; Galushka, S V; Ostapchenko, D V; Shishkina, E V

    2000-01-01

    Mechanical ventilation of the lungs (MVL) with positive end expiratory pressure (PEEP) is difficult in patients with unilateral lung damage because of uneven distribution of volumes and pressures in the involved and intact lungs. Harmful effects are easier manifested under such conditions. Selective MVL with selective PEEP is widely used abroad for optimizing MVL, but this method is rather expensive and is not devoid of shortcomings. Our study carried out in 32 patients with unilateral lung involvement showed that traditional MVL with general PEEP can effectively (in 75% cases) regulate gaseous exchange and decrease its untoward effects if MVL is performed with the patient lying on the healthy side and not supine. MVL in patients with unilateral lung injury lying on the healthy side can be a simpler and cheaper alternative to selective MVL with selective PEEP. PMID:10833838

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

    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

  2. Deadspace breathing as a screening test for early lung damage

    Breathing through added external deadspace (V/sub Dext/) was found to increase the tidal volume of normal dogs in order to achieve alveolar ventilation adequate for gas exchange. Addition of V/sub Dext/ did not alter alveolar-arterial gas gradients or cardiovascular function. Respiratory patterns during V/sub Dext/ breathing were compared with variables measured during treadmill exercise to investigate deadspace breathing as an indicator of early lung dysfunction caused by radiation pneumonitis in dogs. Dogs were evaluated clinically, radiographically and by pulmonary function tests at rest before and after inhaling 144Ce in fused aluminosilicate particles. By 4 mo after inhalation of 32 to 50 μCi/kg 144Ce, there were increases in respiratory frequency and minute volume during V/sub Dext/ breathing and in minute volume and the ventilatory equivalent for O2 while running. No other significant functional, radiographic or clinical changes were noted. The dogs were sacrificed and scattered foci of inflammation were found in their lungs. Deadspace testing detected early, subclinical lung alterations with a sensitivity and at a time identical to treadmill testing and did not require whole-body exercise or training

  3. Acute pulmonary injury: high-resolution CT and histopathological spectrum

    Obadina, E T; Torrealba, J M; Kanne, J P

    2013-01-01

    Acute lung injury usually causes hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS). Although diffuse alveolar damage is the hallmark of ARDS, other histopathological patterns of injury, such as acute and fibrinoid organising pneumonia, can be associated with acute respiratory failure. Acute eosinophilic pneumonia can also cause acute hypoxaemic respiratory failure and mimic ARDS. This pictorial essay reviews the high-resolution CT findings of acute lung injury and ...

  4. NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury

    LI Yang; Liu, Yong; Peng, XiangPing; Liu, Wei; Zhao, FeiYan; Feng, Dandan; Han, Jianzhong; Huang, Yanhong; Luo, Siwei; Li, Lian; Yue, Shao Jie; Cheng, QingMei; Huang,Xiaoting; Luo, Ziqiang

    2015-01-01

    Background Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice. Methods C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were ra...

  5. Interactive effects of hypoxia, carbon monoxide and acute lung injury on oxygen transport and aerobic capacity.

    Crocker, George H; Jones, James H

    2016-05-01

    This study determined how breathing hypoxic gas, reducing circulatory capacitance for O2 by breathing CO, and impairing pulmonary gas exchange by acutely injuring the lungs interact to limit cardiopulmonary O2 delivery, O2 extraction and maximal aerobic capacity (VO2max). Five goats ran on a treadmill at VO2max following oleic-acid induced acute lung injury that impaired pulmonary gas exchange, after partial recovery or with no acute lung injury. Goats breathed normoxic or hypoxic inspired gas fractions (FIO2 0.21 or 0.12) with and without small amounts of CO to maintain carboxyhemoglobin fractions (FHbCO) of 0.02 or 0.30. With the exception of elevated FHbCO with acute lung injury (P=0.08), all combinations of hypoxia, elevated FHbCO and acute lung injury attenuated the reduction in VO2max by 15-27% compared to the sum of each treatment's individual reduction in VO2max when administered separately. Simultaneous administration of two treatments attenuated the reduction in VO2max by attenuating the decrease in cardiopulmonary O2 delivery, not synergistically increasing O2 extraction. PMID:26845454

  6. Effect of Lung Recruitment Maneuver in Children with Acute Lung Injury

    Nemat Bilan

    2016-05-01

    Full Text Available Background Acute lung injury (ALI is defined as PaO2/FiO2 less than 300 with bilateral pulmonary infiltrates, without pressure is the top of the left atrium. Early diagnosis and treatment of pediatric ALI and find new cases is very important. Accurate diagnosis and effective steps to treating these patients is essential in the outcome of ALI. This study was conducted to show the impact of recruitment in the treatment of ALI patients. Materials and Methods This clinical trial study was conducted in Pediatric Educational-Medical center of Tabriz University of Medical Sciences (Tabriz, Iran and 42 patients with ALI were enrolled. All patients were underwent echocardiography. The patients were divided in 2 groups randomly (intervention and control groups consisted of 21 patients for each group. Patients were followed for 6 months to be evaluated in terms of clinical status and mortality. Results Difference on level of PaO2 in intervention group was -26±4 in comparison to the control group which was -4±4 (P

  7. Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1

    GAO, ZHENMING; Xu, Junfeng; Sun, Deguang; ZHANG, Rixin; LIANG, RUI; Wang, Liming; Fan, Rong

    2014-01-01

    Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on ...

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

    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 H2O, 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

  9. Renin-angiotensin system and its role in hyperoxic acute lung injury.

    Zhang, P X; Han, C H; Zhou, F J; Li, L; Zhang, H M; Liu, W W

    2016-01-01

    Oxygen is essential to sustain life, but at a high partial pressure oxygen may cause toxicity to the human body. These injuries to the lung are known as hyperoxic acute lung injury [HALI]). To date, numerous studies have been conducted to investigate the pathogenesis of HALI, for which some hypotheses have been proposed. Accumulating evidence indicates that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of some lung diseases, including acute lung injury (ALI), chronic obstructive pulmonary disease (COPD) and HALI. In this review, we briefly introduce the classic RAS, local (tissue) RAS and intracellular RAS, and we summarize findings on the relationship between local/classic RAS and HALI. The importance--and ambiguity--of the results of these studies indicate a need for further investigations of the RAS and its role in the patho- genesis of HALI. PMID:27416692

  10. Targeting DNA Damage Response in the Radio(Chemo)therapy of Non-Small Cell Lung Cancer

    Ling Li; Tao Zhu; Yuan-Feng Gao; Wei Zheng; Chen-Jing Wang; Ling Xiao; Ma-Sha Huang; Ji-Ye Yin; Hong-Hao Zhou; Zhao-Qian Liu

    2016-01-01

    Lung cancer is the leading cause of cancer death worldwide due to its high incidence and mortality. As the most common lung cancer, non-small cell lung cancer (NSCLC) is a terrible threat to human health. Despite improvements in diagnosis and combined treatments including surgical resection, radiotherapy and chemotherapy, the overall survival for NSCLC patients still remains poor. DNA damage is considered to be the primary cause of lung cancer development and is normally recognized and repair...

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

    The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [3H]serotonin and the extravascular volume accessible to [14C]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

  12. Fas and Fas Ligand Are Up-Regulated in Pulmonary Edema Fluid and Lung Tissue of Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome

    Albertine, Kurt H; Soulier, Matthew F.; Wang, Zhengming; Ishizaka, Akitoshi; Hashimoto, Satoru; Zimmerman, Guy A.; Matthay, Michael A; Lorraine B. Ware

    2002-01-01

    Apoptosis mediated by Fas/Fas ligand (FasL) interaction has been implicated in human disease processes, including pulmonary disorders. However, the role of the Fas/FasL system in acute lung injury (ALI) and in the acute respiratory distress syndrome (ARDS) is poorly defined. Accordingly, we investigated both the soluble and cellular expression of the Fas/FasL system in patients with ALI or ARDS. The major findings are summarized as follows. First, the soluble expression of the Fas/FasL system...

  13. The utility of clinical predictors of acute lung injury: towards prevention and earlier recognition

    Levitt, Joseph E.; Matthay, Michael A

    2010-01-01

    Despite significant advances in our understanding of the pathophysiology of acute lung injury, a lung-protective strategy of mechanical ventilation remains the only therapy with a proven survival advantage. Numerous pharmacologic therapies have failed to show benefit in multicenter clinical trials. The paradigm of early, goal-directed therapy of sepsis suggests greater clinical benefit may derive from initiating therapy prior to the onset of respiratory failure that requires mechanical ventil...

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

    Torii Y; Shimizu T; Yokoi T; Sugimoto H; Katashiba Y; Ozasa R; Fujita S; Adachi Y; Maki M.; Nomura S

    2011-01-01

    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) syndro...

  15. Transfusion related acute lung injury with massive pulmonary secretion during cardiac surgery. A case report

    Teodori, Julien; Rampersad, Kamal; Teodori, Giovanni; Roopchand, Roland; Angelini, Gianni Davide

    2014-01-01

    A Indo-Caribbean patient undergoing cardiac surgery developed Transfusion Related Acute Lung Injury (TRALI) with massive endobronchial secretion of clear fluid mimicking severe pulmonary edema. Hypoxemia and lung stiffness were so severe that didn’t allow closure of the sternum on completion of surgery. The patient was treated with invasive ventilation, high positive pressure and % FiO2 and aggressive endotracheal suction. After several hours, secretions reduced spontaneously and the patient ...

  16. Pulmonary vascular-bronchial interactions: acute reduction in pulmonary blood flow alters lung mechanics

    Schulze-Neick, I; Penny, D; Derrick, G; Dhillon, R; Rigby, M.; Kelleher, A.; Bush, A; Redington, A

    2000-01-01

    BACKGROUND—Postoperative pulmonary hypertension in children after congenital heart surgery is a risk factor for death and is associated with severe acute changes in both pulmonary vascular resistance and lung mechanics.
OBJECTIVE—To examine the impact of changes in pulmonary blood flow on lung mechanics in preoperative children with congenital heart disease, in order to assess the cause-effect relation of pulmonary vascular-bronchial interactions.
DESIGN—Prospective, cross sectional study.
SE...

  17. Increased Extravascular Lung Water Reduces the Efficacy of Alveolar Recruitment Maneuver in Acute Respiratory Distress Syndrome

    Alexey A. Smetkin; Kuzkov, Vsevolod V; Eugeny V. Suborov; Bjertnaes, Lars J; Kirov, Mikhail Y.

    2012-01-01

    Introduction. In acute respiratory distress syndrome (ARDS) the recruitment maneuver (RM) is used to reexpand atelectatic areas of the lungs aiming to improve arterial oxygenation. The goal of our paper was to evaluate the response to RM, as assessed by measurements of extravascular lung water index (EVLWI) in ARDS patients. Materials and Methods. Seventeen adult ARDS patients were enrolled into a prospective study. Patients received protective ventilation. The RM was performed by applying a ...

  18. Transfusion-related acute lung injury following coronary artery bypass graft surgery.

    Bitargil, M; Arslan, C; Başbuğ, H S; Göçer, H; Günerhan, Y; Bekov, Y Y

    2015-11-01

    Blood transfusion is sometimes a necessary procedure during or following coronary artery bypass graft (CABG) surgery. However, transfusion-related acute lung injury (TRALI)/possible TRALI is a rare and fatal complication and characterized by acute hypoxemia and non-cardiogenic pulmonary edema that occurs within 6 hours following a transfusion. Anti-leukocyte antibodies or, possibly, other bioactive substances cause inflammation and capillary endothelial destruction in susceptible recipients' lungs. Prompt diagnosis and mechanical ventilatory support are important. A successful treatment of two male patients following CABG surgery, compatible with TRALI/possible TRALI, is presented here. PMID:25575703

  19. Perfusatory recovery of the grafted lung during convalescence from acute rejection.

    Yamamoto, H; Okada, M; Tobe, S; Tsuji, F; Ohbo, H; Yamashita, C

    2000-01-01

    The aim of this study was to evaluate whether or not perfusatory recovery of the grafted lung occurs is the early stage of convalesce from acute rejection following a single lung transplantation. Eight adult mongrel dogs underwent an allotransplantation of the left lung with treatment of 10 mg/kg cyclosporine and 4 mg/kg azathioprine. Doppler flow probes were placed to the ascending aorta and the left pulmonary artery. Immunosuppressant therapy was discontinued to induce rejection after postoperative day 14. When the left pulmonary artery flow rate (l-PAFR) decreased to less than 20%, methylprednisolone (20 mg/kg) was administered for 3 days along with a resumption of cyclosporine and azathioprine. Pulmonary circulation and chest roentgenograms were evaluated every day through the rejection episode. An open lung biopsy was also performed in each dog to obtain specimens of the grafts and native lungs for histologic examination. When l-PAFR decreased to less than 20%, mild acute rejection was found in all dogs. l-PAFR increased significantly on the third day after methylprednisolone treatment. Thereafter, a histologic examination revealed minimal acute rejection in one dog and no abnormality in seven dogs. The perfusatory recovery of the grafted lung was thought to reflect the histological change in the course of convalescence. PMID:10664339

  20. 17β-estradiol protects the lung against acute injury: possible mediation by vasoactive intestinal polypeptide.

    Hamidi, Sayyed A; Dickman, Kathleen G; Berisha, Hasan; Said, Sami I

    2011-12-01

    Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ERα and ERβ and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60-90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen. PMID:22009726

  1. Brain damage following prophylactic cranial irradiation in lung cancer survivors.

    Simó, Marta; Vaquero, Lucía; Ripollés, Pablo; Jové, Josep; Fuentes, Rafael; Cardenal, Felipe; Rodríguez-Fornells, Antoni; Bruna, Jordi

    2016-03-01

    Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population. PMID:26015269

  2. Red blood cell transfusion and outcomes in patients with acute lung injury, sepsis and shock

    Parsons, Elizabeth C.; Hough, Catherine L.; Seymour, Christopher W; Cooke, Colin R.; Rubenfeld, Gordon D.; Watkins, Timothy R

    2011-01-01

    Introduction In this study, we sought to determine the association between red blood cell (RBC) transfusion and outcomes in patients with acute lung injury (ALI), sepsis and shock. Methods We performed a secondary analysis of new-onset ALI patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial (2000 to 2005) who had a documented ALI risk factor of sepsis or pneumonia and met shock criteria (mean arterial pressure (MAP) < 60 mmHg or vasopressor ...

  3. Effect of Prone Position on Regional Shunt, Aeration, and Perfusion in Experimental Acute Lung Injury

    Richter, Torsten; Bellani, Giacomo; Harris, R. Scott; Melo, Marcos F. Vidal; Winkler, Tilo; Venegas, Jose G.; Musch, Guido

    2005-01-01

    Rationale: The prone position is used to improve gas exchange in patients with acute respiratory distress syndrome. However, the regional mechanism by which the prone position improves gas exchange in acutely injured lungs is still incompletely defined. Methods: We used positron emission tomography imaging of [13N]nitrogen to assess the regional distribution of pulmonary shunt, aeration, perfusion, and ventilation in seven surfactant-depleted sheep in supine and prone positions. Results: In t...

  4. Recipient clinical risk factors predominate in possible transfusion-related acute lung injury

    Toy, PTCY; Bacchetti, P; Grimes, BA; Gajić, O; Murphy, EL; Winters, JL; Gropper, MA; Hubmayr, RD; Matthay, MA; Wilson, GA; Koenigsberg, M; Lee, DC; Hirschler, NV; Lowell, CA; Schuller, RM

    2014-01-01

    © 2014 AABB. Background: Possible transfusion-related acute lung injury (pTRALI) cases by definition have a clear temporal relationship to an alternative recipient risk factor for acute respiratory distress syndrome (ARDS). We questioned whether transfusion factors are important for the development of pTRALI. Study Design and Methods: In this nested case-control study, we prospectively identified 145 consecutive patients with pTRALI and randomly selected 163 transfused controls over a 4-year ...

  5. A diagnosis overlooked: case report of a transfusion related acute lung injury

    Sema Ucak Basat; Sibel Ocak Serin; Berrin Aksakal; Ece Yigit

    2014-01-01

    Transfusion related acute lung injury (TRALI) is a rarely seen and transfusion complication that may develop as a result of transfusion of blood products which contains plasma. TRALI can be mortal if it is not diagnosed and treated promptly. The most important step in management of this complication is to provide the early differential diagnosis of this condition. Hence here in we report a case of TRALI where the patient was firstly misdiagnosed and hospitalized as septic shock and acute hear...

  6. Recipient clinical risk factors predominate in possible transfusion-related acute lung injury

    Toy, P; Bacchetti, P; Grimes, B; Gajic, O; Murphy, EL; Winters, JL; Gropper, MA; Hubmayr, RD; Matthay, MA; Wilson, G; Koenigsberg, M; Lee, DC; Hirschler, NV; Lowell, CA; Schuller, RM

    2015-01-01

    © 2014 AABB. Background: Possible transfusion-related acute lung injury (pTRALI) cases by definition have a clear temporal relationship to an alternative recipient risk factor for acute respiratory distress syndrome (ARDS). We questioned whether transfusion factors are important for the development of pTRALI. Study Design and Methods: In this nested case-control study, we prospectively identified 145 consecutive patients with pTRALI and randomly selected 163 transfused controls over a 4-year ...

  7. Selenium Pretreatment for Mitigation of Ischemia/Reperfusion Injury in Cardiovascular Surgery: Influence on Acute Organ Damage and Inflammatory Response.

    Steinbrenner, Holger; Bilgic, Esra; Pinto, Antonio; Engels, Melanie; Wollschläger, Lena; Döhrn, Laura; Kellermann, Kristine; Boeken, Udo; Akhyari, Payam; Lichtenberg, Artur

    2016-08-01

    Ischemia/reperfusion injury (IRI) contributes to morbidity and mortality after cardiovascular surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Multi-organ damage is associated with substantial decreases of blood selenium (Se) levels in patients undergoing cardiac surgery with CPB. We compared the influence of a dietary surplus of Se and pretreatment with ebselen, a mimic of the selenoenzyme glutathione peroxidase, on IRI-induced tissue damage and inflammation. Male Wistar rats were fed either a Se-adequate diet containing 0.3 ppm Se or supplemented with 1 ppm Se (as sodium selenite) for 5 weeks. Two other groups of Se-adequate rats received intraperitoneal injection of ebselen (30 mg/kg) or DMSO (solvent control) before surgery. The animals were connected to a heart-lung-machine and underwent 45 min of global ischemia during circulatory arrest at 16 °C, followed by re-warming and reperfusion. Selenite and ebselen suppressed IRI-induced leukocytosis and the increase in plasma levels of tissue damage markers (AST, ALT, LDH, troponin) during surgery but did not prevent the induction of proinflammatory cytokines (IL-6, TNF-α). Both Se compounds affected phosphorylation and expression of proteins related to stress response and inflammation: Ebselen increased phosphorylation of STAT3 transcription factor in the heart and decreased phosphorylation of ERK1/2 MAP kinases in the lungs. Selenite decreased ERK1/2 phosphorylation and HSP-70 expression in the heart. Pretreatment with selenite or ebselen protected against acute IRI-induced tissue damage during CPB and DHCA. Potential implications of their different actions with regard to molecular stress markers on the recovery after surgery represent promising targets for further investigation. PMID:27192987

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

    Gupta, Arjun; Sen, Shiraj; Naina, Harris

    2016-01-01

    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. PMID:27053543

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

    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

  10. Neutrophils and their Fcγ receptors are essential in a mouse model of transfusion-related acute lung injury

    Looney, Mark R.; Su, Xiao; Van Ziffle, Jessica A.; Lowell, Clifford A.; Matthay, Michael A

    2006-01-01

    Transfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related mortality. To explore the pathogenesis of TRALI, we developed an in vivo mouse model based on the passive transfusion of an MHC class I (MHC I) mAb (H2Kd) to mice with the cognate antigen. Transfusion of the MHC I mAb to BALB/c mice produced acute lung injury with increased excess lung water, increased lung vascular and lung epithelial permeability to protein, and decreased alveolar fluid clearance. ...

  11. Effects of sigh during pressure control and pressure support ventilation in pulmonary and extrapulmonary mild acute lung injury

    Moraes, Lillian; Santos, Cíntia Lourenco; Santos, Raquel Souza; Cruz, Fernanda Ferreira; Saddy, Felipe; Morales, Marcelo Marcos; Capelozzi, Vera Luiza; Silva, Pedro Leme; Gama de Abreu, Marcelo; Garcia, Cristiane Sousa Nascimento Baez; Pelosi, Paolo; Rocco, Patricia Rieken Macedo

    2014-01-01

    Introduction Sigh improves oxygenation and lung mechanics during pressure control ventilation (PCV) and pressure support ventilation (PSV) in patients with acute respiratory distress syndrome. However, so far, no study has evaluated the biological impact of sigh during PCV or PSV on the lung and distal organs in experimental pulmonary (p) and extrapulmonary (exp) mild acute lung injury (ALI). Methods In 48 Wistar rats, ALI was induced by Escherichia coli lipopolysaccharide either intratrachea...

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

    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.

  13. Small Cell Carcinoma of the Lung Presented as Acute Pancreatitis. Case Report and Review of the Literature

    Abdulzahra Hussain

    2012-11-01

    Full Text Available Context Small cell carcinoma of the lung is an aggressive cancer with gloomy prognosis. Links to acute pancreatitis is extremely rare. Case report We are reporting a 53-year-old patient who was admitted because of acute pancreatitis. She had no history of gallstones, alcohol abuse, medications or any other predisposition for acute pancreatitis. Further investigations of blood, CT of chest abdomen and neck and ultrasound scan of abdomen, bone marrow and neck lymph node biopsies confirmed advanced small cell carcinoma of the lung with hypercalcemia, which was the only definite cause of acute pancreatitis. The patient made good recovery from pancreatitis after controlling the hypercalcemia. She was referred to respiratory team for further management of lung cancer. Conclusion Acute pancreatitis due to hypercalcemia of advanced small cell carcinoma of the lung is an extremely rare condition. Acute pancreatitis due to hypercalcemia should be thoroughly investigated to exclude serious pathology as in our case.

  14. Lung texture in serial thoracic CT scans: correlation with radiologist-defined severity of acute changes following radiation therapy

    This study examines the correlation between the radiologist-defined severity of normal tissue damage following radiation therapy (RT) for lung cancer treatment and a set of mathematical descriptors of computed tomography (CT) scan texture (‘texture features’). A pre-therapy CT scan and a post-therapy CT scan were retrospectively collected under IRB approval for each of the 25 patients who underwent definitive RT (median dose: 66 Gy). Sixty regions of interest (ROIs) were automatically identified in the non-cancerous lung tissue of each post-therapy scan. A radiologist compared post-therapy scan ROIs with pre-therapy scans and categorized each as containing no abnormality, mild abnormality, moderate abnormality, or severe abnormality. Twenty texture features that characterize gray-level intensity, region morphology, and gray-level distribution were calculated in post-therapy scan ROIs and compared with anatomically matched ROIs in the pre-therapy scan. Linear regression and receiver operating characteristic (ROC) analysis were used to compare the percent feature value change (ΔFV) between ROIs at each category of visible radiation damage. Most ROIs contained no (65%) or mild abnormality (30%). ROIs with moderate (3%) or severe (2%) abnormalities were observed in 9 patients. For 19 of 20 features, ΔFV was significantly different among severity levels. For 12 features, significant differences were observed at every level. Compared with regions with no abnormalities, ΔFV for these 12 features increased, on average, by 1.5%, 12%, and 30%, respectively, for mild, moderate, and severe abnormalitites. Area under the ROC curve was largest when comparing ΔFV in the highest severity level with the remaining three categories (mean AUC across features: 0.84). In conclusion, 19 features that characterized the severity of radiologic changes from pre-therapy scans were identified. These features may be used in future studies to quantify acute normal lung tissue damage

  15. Risk factors and outcome of transfusion-related acute lung injury in the critically ill : A nested case-control study

    Vlaar, Alexander P. J.; Binnekade, Jan M.; Prins, David; van Stein, Danielle; Hofstra, Jorrit J.; Schultz, Marcus J.; Juffermans, Nicole P.

    2010-01-01

    Objectives: To determine the incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of critically ill patients. Design: In a retrospective cohort study, patients with transfusion-related acute lung injury were identified using the consensus criteria of acute lung i

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

    Reactive O2 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 O2 species involved in lung O2 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 O2 consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H2O2 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 O2 consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O2 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 H2O2 production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O2 consumption may account for an augmented Nox activity, causing an increased O2·− 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 O2 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 O2 consumption. • Exposure to ROFA produces alterations in mitochondrial function. • ΔΨm decrease in state 3 may be responsible

  17. C-Reactive Protein and Complement Are Important Mediators of Tissue Damage in Acute Myocardial Infarction

    Griselli, M; Herbert, J.; Hutchinson, W. L.; Taylor, K. M.; Sohail, M; Krausz, T.; Pepys, M. B.

    1999-01-01

    Myocardial infarction in humans provokes an acute phase response, and C-reactive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct. The peak plasma CRP value is strongly associated with postinfarct morbidity and mortality. Human CRP binds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhance...

  18. Clearance of aerosolized Tc-99m DTPA from normal vs. acutely smoke-injured dog lungs

    Acute cigarette smoke exposure is known to reversibly increase the clearance rate of aerosolized DTPA from human lungs. The authors studied DTPA clearance after acute severe plywood smoke exposure, on the order of that experienced by burn victims, since current diagnostic methods (Xe-133 and radiographs) for major inhalation injury are insensitive and/or non-specific. Smoke generated from burning plywood sawdust and kerosene was delivered via endotracheal tube at 370C. Skin burns were not inflicted (so the pulmonary consequences of thermal injury were not factors). Chest radiographs and Xe-133 studies were obtained before and after smoke injury but before DTPA aerosol delivery. Six normal and 7 smoke-exposed anesthetized mongrel dogs were studied with 3 mCi of Tc-99m DTPA delivered by aerosol for 5 minutes. Pulmonary Tc-99m DTPA activity was quantitated by computer. Data were acquired over the lungs at 1 frame per 10 secs. for 16 minutes, and the t/sub 1/2/ of DTPA washout from the lungs was calculated. The mean t/sub 1/2/ of 6 normal dogs was 36.52 min. (S.D. 17.73), while the t/sub 1/2/ of 7 smoke-injured dogs was 6.08 min. (S.D. 1.99). The longest t/sub 1/2/ of an injured lung (9.68 min.) was slightly more than half of the shortest t/sub 1/2/ of a normal lung (15.36 min). Thus, acutely smoke-injured dog lungs clear Tc-99m DTPA much faster than normal lungs, consistent with an increase in lung epithelial permeability. This technique may be promising clinically, since early diagnosis of inhalation injury is important for optimal therapy

  19. Treatment with ginkgo biloba extract protects rats against acute pancreatitis-associated lung injury by modulating alveolar macrophage

    Xu, Xiao-Wu; Yang, Xiao-Min; Bai, Yong-Heng; Zhao, Yan-Rong; SHI, GONG-SHENG; Zhang, Jian-Guo; Zheng, Yi-Hu

    2014-01-01

    Introduction Acute pancreatitis (AP) protease release induces lung parenchymal destruction via inflammatory mediators. Ginkgo biloba has been reported to have anti-inflammatory effects. Aim To evaluate the effect of ginkgo biloba extract on experimental acute pancreatitis-associated lung injury in the rat and to investigate the underlying mechanisms. Material and methods Acute pancreatitis was induced in rats by injection of 5% sodium taurocholate into the biliary pancreatic duct. Ginkgo bilo...

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

    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.

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

    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.)

  2. DNA-damage effect of polycyclic aromatic hydrocarbons from urban area, evaluated in lung fibroblast cultures

    This study was designed to biomonitor the effect of PAH extracts from urban areas on the DNA of lung cell cultures. The analyses of the polycyclic aromatic hydrocarbons (PAHs) were performed in atmospheric PM2.5 and PM10 collected at three sampling sites with heavy traffic located in the Metropolitan Area of Porto Alegre (MAPA) (Brazil). The concentrations of 16 major PAHs were determined according to EPA. Comet assay on V79 hamster lung cells was chosen for genotoxicity evaluation. Temperature, humidity, and wind speed were recorded. With regard to the damage index, higher levels were reported in the extract of particulate matter samples from the MAPA during the summer. High molecular weight compounds showed correlation with DNA damage frequency and their respective carcinogenicity. - Highlights: ► Cell line V79 was used to assess the effect of PAHs in PM2.5 and PM10 from urban area. ► Temperature showed a significant seasonal variation with the level of DNA damage. ► PAHs with higher molecular weight contributed to higher DNA damage levels. - DNA-damage effect of polycyclic aromatic hydrocarbons from urban area, showed difference according to season

  3. Experimental study of lung perfusion scintigraphy with sup(99m)Tc-MAA to radiation damaged lung

    The histological changes including blood flow damage due to the irradiation were studied on the rabbits which received the fractionated irradiation of 60Co from the standpoint of the correlationship with the nuclide concentration of the lesion. 1) The histological changes, such as edema, and the congestion in the alveolar wall, initiated right after the 4,000 R of 60Co irradiation, and they become worse with the increase of irradiation dose and with passage of time. In the group of rabbits which was given 10,000 R of irradiation, the remarkable hyperplasia of the alveolar wall, and emphysema manifested, and the fibrosis of the stroma advanced remarkably. 2) X-ray examination revealed the abnormal shadow in the lung only in the group of 10,000 R irradiation right after the end of irradiation. 3) Digital scintigram revealed that in the groups of less than 8,000 R of irradiation blood flow damage recovered, on the other hand, in the group of 10,000 R irradiation, remarkable damage continued for 3 months. These results were assumed to correspond to the degree of abnormality of the histological findings, such as the hyperplasia of the alveolar wall and the blood vessels, emphysem, and fibrosis. 4) Digital scintigram which was processed with computer provided the clearer image of the degree and extent of blood flow damage than those of the original scintigram. (Mukohata, S.)

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

    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

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

    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

  6. A case of metastasis-induced acute pancreatitis in a patient with small cell lung cancer

    Yamanashi, Keiji; Marumo, Satoshi; Saitoh, Motoh; Kato, Motokazu

    2014-01-01

    Key Clinical Message We report a rare case of metastasis-induced acute pancreatitis (MIAP) from small cell lung cancer (SCLC) diagnosed on autopsy, indicating a diagnosis of MIAP with SCLC. Our case suggests that MIAP can arise as a complication of SCLC and has an extremely poor prognosis.

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

    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.

  8. Attenuation of Acute Lung Inflammation and Injury by Whole Body Cooling in a Rat Heatstroke Model

    Hsi-Hsing Yang

    2009-01-01

    Full Text Available Whole body cooling is the current therapy of choice for heatstroke because the therapeutic agents are not available. In this study, we assessed the effects of whole body cooling on several indices of acute lung inflammation and injury which might occur during heatstroke. Anesthetized rats were randomized into the following groups and given (a no treatment or (b whole body cooling immediately after onset of heatstroke. As compared with the normothermic controls, the untreated heatstroke rats had higher levels of pleural exudates volume and polymorphonuclear cell numbers, lung myloperoxidase activity and inducible nitric oxide synthase expression, histologic lung injury score, and bronchoalveolar proinflammatory cytokines and glutamate, and PaCO2. In contrast, the values of mean arterial pressure, heart rate, PaO2, pH, and blood HCO3− were all significantly lower during heatstroke. The acute lung inflammation and injury and electrolyte imbalance that occurred during heatstroke were significantly reduced by whole body cooling. In conclusion, we identified heat-induced acute lung inflammation and injury and electrolyte imbalance could be ameliorated by whole body cooling.

  9. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  10. Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice.

    Yang Xu

    Full Text Available BACKGROUND: Acute respiratory distress syndrome (ARDS is a severe and life-threatening acute lung injury (ALI that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK-MAPK pathway, in lipopolysaccharide (LPS-induced acute lung inflammation. METHODS: Wild-type (WT mice and Spred-2(-/- mice were exposed to intratracheal LPS (50 µg in 50 µL PBS to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2(-/- mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. RESULTS: LPS-induced acute lung inflammation was significantly exacerbated in Spred-2(-/- mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-α, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2(-/- mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. CONCLUSIONS: The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls

  11. An integrated physiology model to study regional lung damage effects and the physiologic response

    Shelley, David A; Sih, Bryant L; Ng, Laurel J

    2014-01-01

    Background This work expands upon a previously developed exercise dynamic physiology model (DPM) with the addition of an anatomic pulmonary system in order to quantify the impact of lung damage on oxygen transport and physical performance decrement. Methods A pulmonary model is derived with an anatomic structure based on morphometric measurements, accounting for heterogeneous ventilation and perfusion observed experimentally. The model is incorporated into an existing exercise physiology mode...

  12. Lung damage induced by butylated hydroxytoluene in mice. Biochemical, cellular, and morphologic characterization.

    Smith, L J

    1984-11-01

    This study was designed to characterize the biochemical, cellular, and morphologic events produced in mice by butylated hydroxytoluene (BHT) and to relate these events to changes in extracellular angiotensin-converting enzyme (ACE) activity. On Day 1 after the administration of BHT, bronchoalveolar lavage (BAL) ACE activity increased 4-fold (p less than 0.001), its specific activity relative to BAL protein increased 3-fold (p less than 0.001), and both type 1 cell damage and endothelial cell damage were detected by electron microscopy. The early increase in BAL ACE activity preceded changes in plasma ACE levels, BAL cell number, protein, lactate, and lactate dehydrogenase (LDH) activity in both plasma and BAL, and the ACE content of alveolar macrophages. On Day 2, BAL ACE activity increased 9-fold, BAL protein increased 4-fold (p less than 0.001), BAL LDH activity increased 34% (p less than 0.05), and the BAL cell count doubled (p less than 0.01). Changes in each animal's appearance, body weight, wet and dry lung weights, and plasma ACE levels occurred between Days 3 and 5. The BAL differential cell count, which consisted of greater than 95% macrophages in uninjured mice, did not change until Day 5 when there was a small increase in polymorphonuclear leukocytes (PMN). On Day 7, the number of PMN peaked, and some of the other measures of lung injury began returning toward normal. These results indicate that BAL ACE activity is a sensitive, early marker of BHT-induced lung injury, which appears to reflect damage to the cells of the alveolar-capillary barrier. In addition, PMN do not appear to play a major role in this model of lung injury. Because of its effects on angiotensin, bradykinin, and prostaglandins, the early release of ACE from damaged cells may modulate the subsequent injury. PMID:6093659

  13. Dosimetric and Microdosimetric approach for the estimation of radon - induced damages in human lungs

    In this paper the estimation of radiation risk of radon and radon progen on induced damages in human lungs is presented. For estimation of radiation risk dosimetric and microdosimetric approach was used. The quality factor in the bronchial an and bronchial region were calculated, they are for homogeneous and heterogeneous distribution, respectively: 16.02 for all cells; 16.72 for secretory cells (BB) and 19.02 for secretory cells (bb); and 12.70 for basal cells

  14. Lung mechanics in the aging lung and in acute lung injury. Studies based on sinusoidal flow modulation.

    Bitzén, Ulrika

    2006-01-01

    Knowledge about lung mechanics is of interest in intensive care to adjust mechanical ventilation and in the lung laboratory for diagnostics and evaluation of patients with various kinds of respiratory diseases. In mechanical ventilation a single inspiratory elastic pressure-volume (Pel/V) curve is difficult to interpret due to continuing re-expansion of collapsed lung units over a large pressure interval. However, the volume shifts between multiple inspiratory Pel/V curves recorded at ...

  15. Alleviation of acute radiation damages by post-irradiation treatments

    Radiation induced hematopoietic and gastro-intestinal damages in mice were tried to alleviate experimentally by post-treatment. Combined treatment of OK-432 and aztreonam clearly prevented the radiation induced sepsis and elevated the survival rate in mice; the survival was 80% in the OK-432 plus aztreonam group while it was 55% in the group treated with OK-432 alone and 0% with saline. Irsogladine maleate, an anti-ulcer drug, increased the survival rate of jejunal crypt stem cells with a clear dose-related trend. The D0 for irsogladine maleate was 2.8 Gy although it was 2.3 Gy for saline, These findings suggest that some conventional drugs are effective for radiation induced hematopoietic and gastro-intestinal damages and the possibility that they can be applied for people exposed to radiation accidentally. (author)

  16. Role of Airway Recruitment and Derecruitment in Lung Injury

    Ghadiali, S. N.; Huang, Y.

    2011-01-01

    The mechanical forces generated during the ventilation of patients with acute lung injury causes significant lung damage and inflammation. Low-volume ventilation protocols are commonly used to prevent stretch-related injury that occurs at high lung volumes. However, the cyclic closure and reopening of pulmonary airways at low lung volumes, i.e., derecruitment and recruitment, also causes significant lung damage and inflammation. In this review, we provide an overview of how biomedical enginee...

  17. Role of damage control enterostomy in management of children with peritonitis from acute intestinal disease

    Ameh, Emmanuel A; Michael A Ayeni; Stephen A Kache; Philip M Mshelbwala

    2013-01-01

    Background: Intestinal anastomosis in severely ill children with peritonitis from intestinal perforation, intestinal gangrene or anastomotic dehiscence (acute intestinal disease) is associated with high morbidity and mortality. Enterostomy as a damage control measure may be an option to minimize the high morbidity and mortality. This report evaluates the role of damage control enterostomy in the treatment of these patients. Materials and Methods: A retrospective review of 52 children with acu...

  18. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury.

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F; Liu, Boyi; Kaelberer, Melanie M; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S; Ye, Guosen; Willette, Robert N; Thorneloe, Kevin S; Bradshaw, Heather B; Matalon, Sadis; Jordt, Sven-Eric

    2014-07-15

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  19. Human amniotic fluid stem cells labeled with up-conversion nanoparticles for imaging-monitored repairing of acute lung injury.

    Xu, Yunyun; Xiang, Jian; Zhao, He; Liang, Hansi; Huang, Jie; Li, Yan; Pan, Jian; Zhou, Huiting; Zhang, Xueguang; Wang, Jiang Huai; Liu, Zhuang; Wang, Jian

    2016-09-01

    Human amniotic fluid stem (hAFS) cells have generated a great deal of excitement in cell-based therapies and regenerative medicine. Here, we examined the effect of hAFS cells labeled with dual-polymer-coated UCNP-PEG-PEI nanoparticles in a murine model of acute lung injury (ALI). We observed hAFS cells migration to the lung using highly sensitive in vivo upconversion luminescence (UCL) imaging. We demonstrated that hAFS cells remained viable and retained their ability to differentiate even after UCNP-PEG-PEI labeling. More importantly, hAFS cells displayed remarkable positive effects on ALI-damaged lung tissue repair compared with mouse bone marrow mesenchymal stem cells (mBMSCs), which include recovery of the integrity of alveolar-capillary membrane, attenuation of transepithelial leukocyte and neutrophil migration, and down-regulation of proinflammatory cytokine and chemokine expression. Our work highlights a promising role for imaging-guided hAFS cell-based therapy in ALI. PMID:27244692

  20. The effect of fibreoptic bronchoscopy in acute respiratory distress syndrome: experimental evidence from a lung model.

    Nay, M-A; Mankikian, J; Auvet, A; Dequin, P-F; Guillon, A

    2016-02-01

    Flexible bronchoscopy is essential for appropriate care during mechanical ventilation, but can significantly affect mechanical ventilation of the lungs, particularly for patients with acute respiratory distress syndrome. We aimed to describe the consequences of bronchoscopy during lung-protective ventilation in a bench study, and thereby to determine the optimal diameter of the bronchoscope for avoiding disruption of the protective-ventilation strategy during the procedure. Immediately following the insertion of the bronchoscope into the tracheal tube, either minute ventilation decreased significantly, or positive end-expiratory pressure increased substantially, according to the setting of the inspiratory pressure limit. The increase in end-expiratory pressure led to an equivalent increase in the plateau pressure, and lung-protective ventilation was significantly altered during the procedure. We showed that a bronchoscope with an external diameter of 4 mm (or less) would allow safer bronchoscopic interventions in patients with severe acute respiratory distress syndrome. PMID:26559154

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

    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.

  2. SPECT perfusion lung scintigraphy in children with chronic pulmonary damage: Preliminary results of a prospective study

    The aim of this study was to describe SPECT perfusion lung scintigraphy findings in symptomatic children with chronic pulmonary damage. Material and Method: We studied 111 children (average age:3.9 yr, range:1 month- 15 yr, 61.3% boys) with chronic pulmonary pathology. The most common clinical diagnosis reported in this population were recurrent bronchopneumonia (45.9%), unknown origin chronic pulmonary damage (36.9%), chronic obstructed bronchitis (27.9%), adenovirus bronchopneumonia sequelae (27.9%) and bronchopulmonary dysplasia (14.4%). The SPECT lung perfusion scintigraphy (LS) was performed in a SMV DST XLi two headed gammacamera, 64x64 matrix, 32 steps of 15 sec each, using a HRLE collimator, after i.v. injection of a age-adjusted dose of Tc99m-MAA. The images were reconstructed using a iterative-post filter method and displayed in tomographic slices and 3D form. We took also planar images in frontal and posterior projections to assess the differential perfusion. The studies were separated according to scintigraphy findings and gender. Results: Ninety eight (88.3%) of realized LS were abnormal (59.2% boys). Fifty three (54.1%) of abnormal scans showed bilateral alterations, being this finding significantly (p:0.034) more frequent in boys (63.8% bilateral lesions) than in girls (40.0% bilateral lesions). When unilateral altered scans were analyzed, the right lung was more frequently affected than left lung (73.5% vs 26.5%) (p:0.002). Of whole abnormal group, 19.4% had diffuse perfusion alterations, 46.9% showed focal alterations and 33.7% had a mixed diffuse-focal pattern. In focal alterations group, the majority presented a segmental distribution (83.7%), being the more frequent localizations the right inferior lobe (39.8%), right upper lobe (34.7%) and left inferior lobe (34.7%). Sixteen patients (16,3%) had focal non-segmental alterations, being situated mainly in upper middle of right lung (47.6%). The range of differential perfusion quantification in

  3. Modifications of lung clearance mechanisms by acute influenza A infection

    Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient

  4. Does a conservative fluid management strategy in the perioperative management of lung resection patients reduce the risk of acute lung injury?

    Evans, Robert G.; Naidu, Babu

    2012-01-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether a conservative fluid management strategy in the perioperative management of lung resection patients is associated with a reduced incidence of postoperative acute lung injury (PALI) and/or acute respiratory distress syndrome (ARDS) in the recovery period. Sixty-seven papers were found using the reported search, of which 13 level III and 1 level IV evidence studies repres...

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

    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

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

    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

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

    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. PMID:27048661

  8. Mesenchymal Stem Cell Attenuates Neutrophil-predominant Inflammation and Acute Lung Injury in an In Vivo Rat Model of Ventilator-induced Lung Injury

    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 PM...

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

    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.

  10. Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice

    Qiao, Ying-Ying; Liu, Xiao-Qin; Xu, Chang-Qin; Zhang, Zheng; Xu, Hong-Wei

    2016-01-01

    AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved. METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05). CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway. PMID:27275094