WorldWideScience

Sample records for acid lung injury

  1. Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

    Directory of Open Access Journals (Sweden)

    Chih-Cheng Lai

    2014-08-01

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

  2. Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.

    Science.gov (United States)

    Abraham, E; Bursten, S; Shenkar, R; Allbee, J; Tuder, R; Woodson, P; Guidot, D M; Rice, G; Singer, J W; Repine, J E

    1995-02-01

    Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.

  3. Total liquid ventilation reduces oleic acid-induced lung injury in piglets

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; LIU Dong-hai; ZHANG Yan-bo; LIU Ai-jun; FAN Xiang-ming; QIAO Chen-hui; WANG Qiang

    2013-01-01

    Background Pediatric patients are susceptible to lung injury that does not respond to traditional therapies.Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury.The aim of this study is to investigate the effect of total liquid ventilation on oleic acid (OA)-induced lung injury in piglets.Methods Twelve Chinese immature piglets were induced acute lung injury by OA.Twelve piglets were randomly treated with conventional gas ventilation (control group) or total liquid ventilation (study group) for 240 minutes.Samples for blood gas analysis were collected before,and at 60-minute intervals after OA-induced lung injury.The degree of lung injury was quantified by histologic examination.The inflammatory cells and the levels of IL-1β,IL-6,IL-10 and TNF-α in plasma,tissue and bronchoalveolar lavage were analyzed.Results Neutrophil and macrophage counts in bronchoalveolar lavage were significantly decreased in the study group (P<0.05).The total lung injury score was also reduced in the study group (P<0.05).The cconcentrations of IL-1β,IL-6,IL-10and TNF-α in plasma,tissue and bronchoalveolar lavage were significantly reduced in the study group (P<0.05).Conclusions Total liquid ventilation reduces biochemical and histologic OA-induced lung injury in piglets.

  4. Effect of terbutaline on alveolar liquid clearance after oleic acid-induced lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    TAO Jun; YANG Tian-de; LI Hong; DU Zhi-yong

    2006-01-01

    Objective: To investigate whether terbutaline affects alveolar liquid clearance after oleic acid-induced lung injury in rats.Methods: Forty healthy Wistar rats ( weighing 250-280 g) were randomly divided into five groups ( n = 8 in each group): the normal control group ( control group),oleic acid injury group ( injury group), terbutaline-treated group (terbutaline group ), terbutaline plus amiloridetreated group (terbutaline + amiloride group ) and terbutaline plus ouabain-treated group (terbutaline + ouabain group). Acute lung injury model was induced by intravenous oleic acid (0. 25 mi/kg body weight). 24 hours later, 1.5 μCi 125I-labeled 5% albumin solution (5 ml/kg body weight) was dripped into the lungs through trachea.The alveolar liquid clearance rate, extravascular lung water content, and arterial blood gas were measured 1 hour thereafter.Results: At 24 hours after infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia,with the alveolar liquid clearance rate decreased by 49.2 % and the extravascular lung water content elevated by 47.9%. Compared with the rats in the injury group,terbutaline (10-4 mol/L ) significantly increased the alveolar liquid clearance rate, decreased the extravascular lung water content and improved hypoxemia. The effect of terbutaline was partly blocked by amiloride and ouabain,which were inhibitors of sodium transport. Terbutaline increased the alveolar liquid clearance rate by 63.7 %, and amiloride and ouabain reduced the alveolar liquid clearance rate by 54.7% and 56.8%, respectively.Conclusions: Terbutaline can accelerate alveolar liquid clearance through increasing sodium transport to attenuate pulmonary edema, thus improving gas exchange,which may have therapeutical effect on pulmonary edema after acute lung injury.

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

    Science.gov (United States)

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

    2013-12-01

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

  6. Low positive end-expiratory pressure does not exacerbate nebulized-acid lung injury in dogs.

    Science.gov (United States)

    Pellett, Andrew A; Welsh, David A; deBoisblanc, Bennett P; Lipscomb, Gary; Johnson, Royce W; Lord, Kevin C; Levitzky, Michael G

    2005-03-01

    It is not clear if low end-expiratory pressures contribute to ventilator-induced lung injury in large animals. We sought to determine whether ventilation with a low level of positive end-expiratory pressure (PEEP) worsens preexisting permeability lung injury in dogs. Lung injury was initiated in 20 mongrel dogs by ventilating with nebulized 3N hydrochloric acid until a lower inflection point (LIP) appeared on the respiratory system pressure-volume loop. One group of 10 dogs was then ventilated for 4 hours with PEEP set below the LIP (low PEEP), whereas the remaining group of dogs was ventilated for the same time period with similar tidal volumes but with PEEP set above the LIP (high PEEP). We found histologic evidence of reduced alveolar volumes in the low-PEEP animals. However, there were no differences in neutrophil infiltration, lung lobe weights, pulmonary capillary hemorrhage or congestion, or arterial endothelin-1 concentration between the 2 protocol groups. In conclusion, we were unable to demonstrate that ventilation with PEEP set below the LIP exacerbates hydrochloric acid-induced lung injury in dogs.

  7. Segmental pulmonary vascular resistances during oleic acid lung injury in rabbits.

    Science.gov (United States)

    Maarek, J M; Grimbert, F

    1994-10-01

    We studied in isolated rabbit lungs the effects of oleic acid (OA) injury on the segmental distribution of vascular resistance. Vascular occlusion pressures were measured in control and OA-injured preparations over 90 min. Capillary filtration coefficient KF,C increased from 0.61 (+/- 0.10) to 0.91 (+/- 0.14) g.min-1.mmHg-1.(100 g)-1 in OA-injured lungs whereas it remained constant in control lungs. Total pulmonary vascular resistance changed little in both control and OA-injured lungs. OA injury resulted in a 15% increase of the double occlusion capillary pressure. In addition, the contribution of the microvascular to the total vascular resistance rose from 8% to 22%. The increase in microvascular resistance was significant 15 min after OA on the arteriolar side and became significant 30 min later on the venular side. Oleic acid injury does not change the total pulmonary vascular resistance but alters the distribution of segmental resistances in the isolated rabbit lung, thereby contributing to the accumulation of lung water in this model of low pressure permeability edema.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  11. Oleic Acid Induces Lung Injury in Mice through Activation of the ERK Pathway

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves-de-Albuquerque

    2012-01-01

    Full Text Available Oleic acid (OA can induce acute lung injury in experimental models. In the present work, we used intratracheal OA injection to show augmented oedema formation, cell migration and activation, lipid mediator, and cytokine productions in the bronchoalveolar fluids of Swiss Webster mice. We also demonstrated that OA-induced pulmonary injury is dependent on ERK1/2 activation, since U0126, an inhibitor of ERK1/2 phosphorylation, blocked neutrophil migration, oedema, and lipid body formation as well as IL-6, but not IL-1β production. Using a mice strain carrying a null mutation for the TLR4 receptor, we proved that increased inflammatory parameters after OA challenges were not due to the activation of the TLR4 receptor. With OA being a Na/K-ATPase inhibitor, we suggest the possible involvement of this enzyme as an OA target triggering lung inflammation.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-07-01

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

  15. Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids.

    Science.gov (United States)

    Yamaguchi, K; Mori, M; Kawai, A; Asano, K; Takasugi, T; Umeda, A; Yokoyama, T

    1992-01-01

    To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a

  16. Changes in liquid clearance of alveolar epithelium after oleic acid-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    陶军; 杨天德; 陈祥瑞; 黄河

    2004-01-01

    Objective:Impaired active fluid transport of alveolar epithelium may involve in the pathogenesis and resolution of alveolar edema. Thc objective of this study was to explore the changes in alveolar epithelial liquid clearance during lung edema following acute lung injury induced by oleic acid. Methods:Forty-eight Wistar rats were randomly divided into six groups, I.e. , injured, amiloride, ouabain, amiloride plus ouabain and terbutaline groups. Twenty- four hours after the induction of acute lung injury by intravenous oleic acid (0.25 ml/kg), 5% albumin solution with 1.5 μCi 125Ⅰ-labeled albumin (5 ml/kg) was delivered into both lungs via trachea. Alveolar liquid clearance (ALC), extravascular lung water ( EVLW ) content and arterial blood gases were measured one hour thereafter.Results: At 24 h after the infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with EVLW increased by 47.9% and ALC decreased by 49.2%. Addition of either 2 × 10-3 M amiloride or 5 × 10-4 M ouabain to the instillation further reduced ALC and increased EVLW. ALC increased by approximately 63.7% and EVLW decreased by 46.9% with improved hypoxemia in the Terbutaline (10-4 M) group, compared those in injured rats. A significant negative correlation was found between the increment of EVLW and the reduction of ALC. Onclusions:Active fluid transport of alveolar epithelium might play a role in the pathogenesis of lung edema in acute lung injury.

  17. Adult Lysophosphatidic Acid Receptor 1-Deficient Rats with Hyperoxia-Induced Neonatal Chronic Lung Disease Are Protected against Lipopolysaccharide-Induced Acute Lung Injury

    Science.gov (United States)

    Chen, Xueyu; Walther, Frans J.; Laghmani, El H.; Hoogeboom, Annemarie M.; Hogen-Esch, Anne C. B.; van Ark, Ingrid; Folkerts, Gert; Wagenaar, Gerry T. M.

    2017-01-01

    Aim: Survivors of neonatal chronic lung disease or bronchopulmonary dysplasia (BPD) suffer from compromised lung function and are at high risk for developing lung injury by multiple insults later in life. Because neonatal lysophosphatidic acid receptor-1 (LPAR1)-deficient rats are protected against hyperoxia-induced lung injury, we hypothesize that LPAR1-deficiency may protect adult survivors of BPD from a second hit response against lipopolysaccharides (LPS)-induced lung injury. Methods: Directly after birth, Wistar control and LPAR1-deficient rat pups were exposed to hyperoxia (90%) for 8 days followed by recovery in room air. After 7 weeks, male rats received either LPS (2 mg kg−1) or 0.9% NaCl by intraperitoneal injection. Alveolar development and lung inflammation were investigated by morphometric analysis, IL-6 production, and mRNA expression of cytokines, chemokines, coagulation factors, and an indicator of oxidative stress. Results: LPAR1-deficient and control rats developed hyperoxia-induced neonatal emphysema, which persisted into adulthood, as demonstrated by alveolar enlargement and decreased vessel density. LPAR1-deficiency protected against LPS-induced lung injury. Adult controls with BPD exhibited an exacerbated response toward LPS with an increased expression of pro-inflammatory mRNAs, whereas LPAR1-deficient rats with BPD were less sensitive to this “second hit” with a decreased pulmonary influx of macrophages and neutrophils, interleukin-6 (IL-6) production, and mRNA expression of IL-6, monocyte chemoattractant protein-1, cytokine-induced neutrophil chemoattractant 1, plasminogen activator inhibitor-1, and tissue factor. Conclusion: LPAR1-deficient rats have increased hyperoxia-induced BPD survival rates and, despite the presence of neonatal emphysema, are less sensitive to an aggravated “second hit” than Wistar controls with BPD. Intervening in LPA-LPAR1-dependent signaling may not only have therapeutic potential for neonatal chronic

  18. Effect of high dose steroids on oleic acid-induced lung injury in rabbits: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hwa Yeon; Yoo, Seung Min [Chung-Ang University Hospital, Seoul (Korea, Republic of)

    2006-02-15

    The purpose of this study is to evaluate the therapeutic efficacy, on the basis of CT findings, of high dose methyl prednisolone for treating acute lung injury that was induced by oleic acid injection. A total of 30 healthy rabbits (1.8-2.2 kg) were included in this study. Group I included 10 rabbits in which 0.2 mL oleic acid was injected through their ear veins. Group IIa included 10 rabbits in which 30 mg/kg methyl prednisolone and 0.2 mL oleic acid were intravenously injected at the same time. Group IIb included 5 rabbits in which 30 mg/kg methyl prednisolone was injected 6 hours prior to the 0.2 mL oleic acid intravenous injection. The other 5 rabbits (Group III) were injected intravenously with 30 mg/kg methyl prednisolone without the oleic acid. After that, 30 mg/kg methyl prednisolone per every 12 hours was injected in the non-sacrificed rabbits of Group II and Group III. Nonenhanced Chest CT scans were performed prior to the 30 minutes, 4 hours, 24 hours, 48 hours, and 72 hours after the intravenous injection of oleic acid or methyl prednisolone. We randomly sacrificed one rabbit of groups I, II and III 30 minutes, 4 hours, 24 hours, 48 hours and 72 hours after CT scanning. The distribution, extent, and pattern of the lesions on the CT scan were analyzed. The analyzed pattern of the lesions was ground glass attenuation, consolidation and interstitial thickening. Pathologic correlation was then done. The main CT findings of Group I were peripheral, wedge shaped, ill-defined ground glass attenuations and /or consolidations. The pathologic findings of Group I were interstitial or intraalveolar edema, intraalveolar hemorrhage and coagulation necrosis. Diffuse ground glass opacities with interstitial thickening were noted in 20% (n=2/10) of Group I and in 60% (n=9/15) of Group II at the 30 minute CT; however, there was no statistical difference between the two groups ({rho} = 0.09). Consolidations with air bronchogram were noted in 22.2% (2/9) of Group I and in

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

    Science.gov (United States)

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

    2015-06-01

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

  20. Successful treatments of lung injury and skin burn due to hydrofluoric acid exposure.

    Science.gov (United States)

    Kono, K; Watanabe, T; Dote, T; Usuda, K; Nishiura, H; Tagawa, T; Tominaga, M; Higuchi, Y; Onnda, M

    2000-06-01

    Recent growth in the electronics and chemical industries has brought about a progressive increase in the use of hydrofluoric acid (HF), along with the concomitant risk of acute poisoning among HF workers. We report severe cases of inhalation exposure and skin injury which were successfully treated by administering a 5% calcium gluconate solution with a nebulizer and applying 2.5% calcium gluconate jelly, respectively. Case 1: A 52-year old worker used HF for surface treatment after welding stainless steel, and was hospitalized with rapid onset of severe dyspnea. On admission to the critical care medical center he had widespread wheezing and crackles in his lungs. Chest radiograph showed a fine diffuse veiling over both lower pulmonary fields. Severe hypocalcemia with high concentrations of F in serum and urine were disclosed. He was immediately given 5% calcium gluconate solution by intermittent positive-pressure breathing (IPPB), utilizing a nebulizer. On the 21st hospital day, chest film and CT scan did not demonstrate any abnormality. He was discharged very much improved on the 22nd hospital day. Case 2: A 35-year old worker at an electronics factory was admitted to his local hospital with severe skin burn on his face and neck after exposure to 100% HF. Treatment began with immediate copious washing with water for 20 min. Calcium gluconate 2.5% gel (HF burn jelly) was applied to the area as a first-aid measure. Persistent high concentrations of serum and urinary F were disclosed for 2 weeks. After treatment with applications of HF burn jelly, he was confirmed as being completely recovered. The present cases and a review of published data suggest that an adequate method of emergency treatment for accidental HF poisoning is necessary.

  1. Mechanism of Retinoic Acid and Mitogen-activated Protein Kinases Regulating Hyperoxia Lung Injury

    Institute of Scientific and Technical Information of China (English)

    LI Wenbin; CHANG Liwen; RONG Zhihui; ZHANG Qianshen; WANG Hua; WANG Hong; LIU Chunmei; LIU Wei

    2006-01-01

    To investigate the protective effect of retinoicacid (RA) on hyperoxic lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs), gastation 21 d SpragueDawley (SD) fetuses (term=22d) were delivered by hysterotomy. Within 12-24 h of birth,premature rat pups were randomly divided into 4 groups (n=12 each): air-exposed control group (group Ⅰ); hyperoxia-exposed group ( group Ⅱ), air-exposed plus RA group (group Ⅲ ), hyperoxia-exposed plus RA group (group Ⅳ). Group Ⅰ ,Ⅲ were kept in room air, and group Ⅱ , Ⅳwere placed in 85 % oxygen. The pups in groups Ⅲ and Ⅳ were intraperitoneally injected with RA (500 μg/kg every day). All lung tissues of premature rat pups were collected at the 4th day after birth. Terminal transferase d-UTP nick end labeling (TUNEL) staining was used for the detection of cell apoptosis. The expression of PCNA was immunohistochemically detected. Western blot analysis was employed for the determination of phosphorylated and total nonphosphorylated ERKs,JNKs or p38. Our results showed that lungs from the pups exposed to hyperoxia for 4 d exhibited TUNEL-positive nuclei increased markedly throughout the parenchyma (P<0.01),and decreased significantly after RA treatment (P<0.01). The index of PCNA-positive cells was significantly decreased (P<0.01), and was significantly increased by RA treatment (P<0.01).The air-space size was significantly enlarged, secondary crests were markedly decreased in hyperoxia-exposed animals. RA treatment improved lung air spaces and secondary crests in air-exposed pups, but had no effect on hyperoxia-exposure pups. Western blotting showed that the amounts of JNK, p38 and ERK proteins in hyperoxia-exposure or RA-treated lung tissues were same as those in untreated lung tissues (P>0.05), whereas activation of these MAPKs was markedly altered by hyperoxia and RA. After hyperoxia exposure, p-ERK1/2, p-JNK1/2 and p-p38 were dramatically increased (P<0

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  3. Partial liquid ventilation decreases tissue and serum tumor necrosis factor-α concentrations in acute lung injury model of immature piglet induced by oleic acid

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; FAN Xiang-ming; LI Xiao-feng; LI Zhi-qiang; WANG Qiang; SUN Li-zhong; LIU Ying-long

    2012-01-01

    Background Pediatric patients are susceptible to lung injury.Acute lung injury in children often results in high mortality.Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor (TNF)-α in an immature piglet model of acute lung injury induced by oleic acid (OA).Methods Twelve Chinese immature piglets were induced acute lung injury by OA.The animals were randomly assigned to two groups of six animals,(1) conventional mechanical ventilation (MV) group and (2) PLV with 10 ml/kg FC-77 group.Results Compared with MV group,the PLV group had better cardiopulmonary variables (P <0.05).These variables included heart rate,mean blood pressure,blood pH,partial pressure of arterial oxygen (PaO2),PaO2/inspired O2 fraction (FiO2) and partial pressure of arterial carbon dioxide (PaCO2).PLV reduced TNF-α levels both in plasma and tissue compared with MV group (P <0.05).Conclusion PLV provides protective effects against TNF-a response in OA-induced acute lung injury in immature piglets.

  4. Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis.

    Science.gov (United States)

    Black, Katharine E; Berdyshev, Evgeny; Bain, Gretchen; Castelino, Flavia V; Shea, Barry S; Probst, Clemens K; Fontaine, Benjamin A; Bronova, Irina; Goulet, Lance; Lagares, David; Ahluwalia, Neil; Knipe, Rachel S; Natarajan, Viswanathan; Tager, Andrew M

    2016-06-01

    Lysophosphatidic acid (LPA) is an important mediator of pulmonary fibrosis. In blood and multiple tumor types, autotaxin produces LPA from lysophosphatidylcholine (LPC) via lysophospholipase D activity, but alternative enzymatic pathways also exist for LPA production. We examined the role of autotaxin (ATX) in pulmonary LPA production during fibrogenesis in a bleomycin mouse model. We found that bleomycin injury increases the bronchoalveolar lavage (BAL) fluid levels of ATX protein 17-fold. However, the LPA and LPC species that increase in BAL of bleomycin-injured mice were discordant, inconsistent with a substrate-product relationship between LPC and LPA in pulmonary fibrosis. LPA species with longer chain polyunsaturated acyl groups predominated in BAL fluid after bleomycin injury, with 22:5 and 22:6 species accounting for 55 and 16% of the total, whereas the predominant BAL LPC species contained shorter chain, saturated acyl groups, with 16:0 and 18:0 species accounting for 56 and 14% of the total. Further, administration of the potent ATX inhibitor PAT-048 to bleomycin-challenged mice markedly decreased ATX activity systemically and in the lung, without effect on pulmonary LPA or fibrosis. Therefore, alternative ATX-independent pathways are likely responsible for local generation of LPA in the injured lung. These pathways will require identification to therapeutically target LPA production in pulmonary fibrosis.-Black, K. E., Berdyshev, E., Bain, G., Castelino, F. V., Shea, B. S., Probst, C. K., Fontaine, B. A., Bronova, I., Goulet, L., Lagares, D., Ahluwalia, N., Knipe, R. S., Natarajan, V., Tager, A. M. Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis.

  5. Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    Guang-ju ZHOU; Hong ZHANG; Sheng-de ZHI; Guo-ping JIANG; Jing WANG; Mao ZHANGI; Jian-xin GAN; Shao-wen XU; Guan-yu JIANG

    2007-01-01

    Aim: To evaluate the protective effect of oral raloxifene on acute lung injury.Methods: Thirty adult, male Sprague-Dawley rats each weighing 180-210 g were used and divided into 3 groups: the raloxifene-lipopolysacchadde (LPS)-HC1 group(n=10), the LPS-raloxifene-HCl group (n=10), and the placebo group (n=10). All the rats were injected intraperitoneally (ip) with 5 mg/kg LPS, and raloxifene (30mg/kg) was orally administered 1 h before and 14 h after LPS injection into the raloxifene-LPS-HCl and the LPS-raloxifene-HCl groups, respectively; the placebo group received nothing. Sixteen hours after LPS injection, all the animals were anesthetized and the femoral artery was cannulated. All the rats received a direct intratracheal (IT) injection ofHCl (pH 1.2; 0.5 mL/kg). The mean arterial pressure(MAP) and blood gas concentrations were measured. Fifteen rats (5 in each group, respectively) underwent a micro positron emission to mography (microPET)scan of the thorax 4 h after HC1 instillation. The wet/dry (W/D) weight ratio determination and histopathological examination were also performed. Results:The rats in the LPS-raloxifene-HC1 group had a lower [18F]fluorodeoxyglucose uptake compared with the rats in the placebo group (4.67±1.33 vs 9.01±1.58,respectively, P<0.01). The rats in the LPS-raloxifene-HC1 group also had a lower histological lung injury score (8.20±1.23 vs 12.6±0.97, respectively, P<0.01) and W/D weight ratio (5.335±0.198 vs 5.886±0.257, respectively, P<0.01) compared to the placebo group. The rats in this group also showed better pulmonary gas exchange and more stable mean arterial pressure (MAP) compared to the placebo group. Conclusion: Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HC1 IT instillation.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  7. Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves de Albuquerque

    2012-01-01

    Full Text Available Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs can be toxic to cells. Increased blood concentration of oleic acid (OLA and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets.

  8. Biomarkers in acute lung injury.

    Science.gov (United States)

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

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

  9. Protective effect of erdosteine against hypochlorous acid-induced acute lung injury and lipopolysaccharide-induced neutrophilic lung inflammation in mice.

    Science.gov (United States)

    Hayashi, K; Hosoe, H; Kaise, T; Ohmori, K

    2000-11-01

    The effect of erdosteine, a mucoactive drug, on hypochlorous acid (HOCl)-induced lung injury, and the lipopolysaccharide (LPS)-induced increase in tumour necrosis factor-alpha (TNF-alpha) production and neutrophil recruitment into the airway, was investigated. Male BALB/c mice were orally administered erdosteine (3-100 mgkg(-1)), ambroxol hydrochloride (ambroxol) (3-30 mgkg(-1)), S-carboxymethyl-L-cysteine (S-CMC) (100-600 mgkg(-1)) or prednisolone (10 mgkg(-1)), 1 h before intratracheal injection of HOCl or LPS. In the HOCl-injected mice, erdosteine markedly suppressed increases in the ratios of lung wet weight to bodyweight and lung dry weight to bodyweight, whereas the other mucoactive drugs ambroxol and S-CMC had little effect. Erdosteine also inhibited the LPS-induced neutrophil influx, although it did not affect the increased level of TNF-alpha in the bronchoalveolar lavage fluid. The results suggest that attenuation of reactive oxygen species and neutrophil recruitment is involved in the clinical efficacy of erdosteine in the treatment of chronic bronchitis.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  11. Effects of minimal lipopolysaccharide-instilled lungs on ventilator-induced lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    LI Ke-zhong; WANG Qiu-jun; SUN Tao; YAO Shang-long

    2007-01-01

    @@ Mechanical ventilation (MV) may aggravate lung injury induced by a variety of injuries, including intratracheal hydrochloric acid instillation,1 intratracheal lipopolysaccharide (LPS) instillation with or without concurrent saline lavage,2 intravenous LPS,3 or intravenous oleic acid.4 However, the mechanism for this detrimental effect of MV is unclear.

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

    Science.gov (United States)

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

    2007-08-01

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

  13. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    T N Hagawane

    2016-01-01

    Results: It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6 levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. Interpretation & conclusions: The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

  14. Mechanisms of enhanced lung injury during sepsis

    DEFF Research Database (Denmark)

    Czermak, B J; Breckwoldt, M; Ravage, Z B;

    1999-01-01

    A major complication in sepsis is progressively impaired lung function and susceptibility to intrapulmonary infection. Why sepsis predisposes the lung to injury is not clear. In the current studies, rats were rendered septic by cecal ligation/puncture and evaluated for increased susceptibility...... to injury after a direct pulmonary insult (deposition of IgG immune complexes or airway instillation of lipopolysaccharide). By itself, cecal ligation/puncture did not produce evidence of lung injury. However, after a direct pulmonary insult, lung injury in septic animals was significantly enhanced...... or treatment with anti-C5a abolished all evidence of enhanced lung injury in septic animals. When stimulated in vitro, bronchoalveolar lavage macrophages from septic animals had greatly enhanced CXC chemokine responses as compared with macrophages from sham-operated animals or from septic animals that had been...

  15. Rabbit lung injury induced by explosive decompression

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the mechanism of rabbit lunginjury caused by explosive decompression. Methods: A total of 42 rabbits and 10 rats were served as the experimental animals. A slow recompressiondecompression test and an explosive decompression test were applied to the animals, respectively. And the effects of the given tests on the animals were discussed. Results: The slow recompression-decompression did not cause an obvious lung injury, but the explosive decompression did cause lung injuries in different degrees. The greater the decompression range was, the shorter the decompression duration was, and the heavier the lung injuries were. Conclusions: Explosive decompression can cause a similar lung injury as shock wave does. The primary mechanical causes of the lung injury might be a tensile strain or stress in the alveolar wall and the pulmonary surface's impacts on the inside wall of the chest.

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

    Science.gov (United States)

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

    2010-12-01

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

  17. Bleomycin-Induced Lung Injury

    Directory of Open Access Journals (Sweden)

    Tomás Reinert

    2013-01-01

    Full Text Available Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and Hodgkin’s lymphoma. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. The mechanism of bleomycin-induced pneumonitis (BIP involves oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and the elaboration of inflammatory cytokines. Ultimately, BIP can progress to lung fibrosis. The diagnosis of BIP is established by the combination of systemic symptoms, radiological and histological findings, and respiratory function tests abnormalities, while other disorders should be excluded. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. In general, the clinical picture is extremely complex. A greater understanding of the BIP pathogenesis may lead to the development of new agents capable of preventing or even treating the injury already present. Physicians who prescribe bleomycin must be aware of the potential pulmonary toxicity, especially in the presence of risk factors. This review will focus on BIP, mainly regarding recent advances and perspectives in diagnosis and treatment.

  18. First-pass studies of acute lung injury.

    Science.gov (United States)

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

    1993-10-01

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

  19. First-pass studies of acute lung injury

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-10-01

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

  20. Stem cells and repair of lung injuries

    Directory of Open Access Journals (Sweden)

    Randell Scott H

    2004-07-01

    Full Text Available Abstract Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung.

  1. Potential Biochemical Mechanisms of Lung Injury in Diabetes

    Science.gov (United States)

    Zheng, Hong; Wu, Jinzi; Jin, Zhen; Yan, Liang-Jun

    2017-01-01

    Accumulating evidence has shown that the lung is one of the target organs for microangiopathy in patients with either type 1 or type 2 diabetes mellitus (DM). Diabetes is associated with physiological and structural abnormalities in the diabetic lung concurrent with attenuated lung function. Despite intensive investigations in recent years, the pathogenic mechanisms of diabetic lung injury remain largely elusive. In this review, we summarize currently postulated mechanisms of diabetic lung injury. We mainly focus on the pathogenesis of diabetic lung injury that implicates key pathways, including oxidative stress, non-enzymatic protein glycosylation, polyol pathway, NF-κB pathway, and protein kinase c pathway. We also highlight that while numerous studies have mainly focused on tissue or cell damage in the lung, studies focusing on mitochondrial dysfunction in the diabetic lung have remained sketchy. Hence, further understanding of mitochondrial mechanisms of diabetic lung injury should provide invaluable insights into future therapeutic approaches for diabetic lung injury.

  2. Neurological outcome after experimental lung injury.

    Science.gov (United States)

    Bickenbach, Johannes; Biener, Ingeborg; Czaplik, Michael; Nolte, Kay; Dembinski, Rolf; Marx, Gernot; Rossaint, Rolf; Fries, Michael

    2011-12-15

    We examined the influences of acute lung injury and hypoxia on neurological outcome. Functional performance was assessed using a neurocognitive test and a neurologic deficit score (NDS) five days before. On experimental day, mechanically ventilated pigs were randomized to hypoxia only (HO group, n=5) or to acute lung injury (ALI group, n=5). Hemodynamics, respiratory mechanics, systemic cytokines and further physiologic variables were obtained at baseline, at the time of ALI, 2, 4 and 8h thereafter. Subsequently, injured lungs were recruited and animals weaned from the ventilator. Neurocognitive testing was re-examined for five days. Then, brains were harvested for neurohistopathology. After the experiment, neurocognitive performance was significantly worsened and the NDS increased in the ALI group. Histopathology revealed no significant differences. Oxygenation was comparable between groups although significantly higher inspiratory pressures occured after ALI. Cytokines showed a trend towards higher levels after ALI. Neurocognitive compromise after ALI seems due to a more pronounced inflammatory response and complex mechanical ventilation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-15

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

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

    OpenAIRE

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

    1985-01-01

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

  5. Relationship between Ulcerative Colitis and Lung Injuries

    Institute of Scientific and Technical Information of China (English)

    Zhi-peng Tang; Jia-wei Wu; Yan-cheng Dai; Ya-li Zhang; Rong-rong Bi

    2015-01-01

    Objective To explore the relationship between ulcerative colitis (UC) and lung injuries by assessing their clinical manifestations and characteristics. Methods From July 2009 to April 2012, 91 UC patients presenting to Longhua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study. According to the scores of disease activity index, the patients were divided into the mild, moderate, and severe groups. Meanwhile, the records of pulmonary symptoms, chest X-ray image, and pulmonary function were reviewed. Results Sixty-eight (74.7%) patients had at least 1 pulmonary symptom, such as cough (38.5%), shortness of breath (27.5%), and expectoration (17.6%). And 77 (84.6%) had at least 1 ventilation abnormality. Vital capacity value was significantly lower in the severe group than that in the mild group (91.82%±10.38%vs. 98.92%±12.12%, P Conclusions Lung injury is a common extraintestinal complication of UC. According to the theory in Traditional Chinese Medicine that the lung and large intestine are related, both the lungs and large intestine should be treated simultaneously.

  6. Fibrogenic Lung Injury Induces Non-Cell-Autonomous Fibroblast Invasion.

    Science.gov (United States)

    Ahluwalia, Neil; Grasberger, Paula E; Mugo, Brian M; Feghali-Bostwick, Carol; Pardo, Annie; Selman, Moisés; Lagares, David; Tager, Andrew M

    2016-06-01

    Pathologic accumulation of fibroblasts in pulmonary fibrosis appears to depend on their invasion through basement membranes and extracellular matrices. Fibroblasts from the fibrotic lungs of patients with idiopathic pulmonary fibrosis (IPF) have been demonstrated to acquire a phenotype characterized by increased cell-autonomous invasion. Here, we investigated whether fibroblast invasion is further stimulated by soluble mediators induced by lung injury. We found that bronchoalveolar lavage fluids from bleomycin-challenged mice or patients with IPF contain mediators that dramatically increase the matrix invasion of primary lung fibroblasts. Further characterization of this non-cell-autonomous fibroblast invasion suggested that the mediators driving this process are produced locally after lung injury and are preferentially produced by fibrogenic (e.g., bleomycin-induced) rather than nonfibrogenic (e.g., LPS-induced) lung injury. Comparison of invasion and migration induced by a series of fibroblast-active mediators indicated that these two forms of fibroblast movement are directed by distinct sets of stimuli. Finally, knockdown of multiple different membrane receptors, including platelet-derived growth factor receptor-β, lysophosphatidic acid 1, epidermal growth factor receptor, and fibroblast growth factor receptor 2, mitigated the non-cell-autonomous fibroblast invasion induced by bronchoalveolar lavage from bleomycin-injured mice, suggesting that multiple different mediators drive fibroblast invasion in pulmonary fibrosis. The magnitude of this mediator-driven fibroblast invasion suggests that its inhibition could be a novel therapeutic strategy for pulmonary fibrosis. Further elaboration of the molecular mechanisms that drive non-cell-autonomous fibroblast invasion consequently may provide a rich set of novel drug targets for the treatment of IPF and other fibrotic lung diseases.

  7. Lung Injury After One-Lung Ventilation: A Review of the Pathophysiologic Mechanisms Affecting the Ventilated and the Collapsed Lung.

    Science.gov (United States)

    Lohser, Jens; Slinger, Peter

    2015-08-01

    Lung injury is the leading cause of death after thoracic surgery. Initially recognized after pneumonectomy, it has since been described after any period of 1-lung ventilation (OLV), even in the absence of lung resection. Overhydration and high tidal volumes were thought to be responsible at various points; however, it is now recognized that the pathophysiology is more complex and multifactorial. All causative mechanisms known to trigger ventilator-induced lung injury have been described in the OLV setting. The ventilated lung is exposed to high strain secondary to large, nonphysiologic tidal volumes and loss of the normal functional residual capacity. In addition, the ventilated lung experiences oxidative stress, as well as capillary shear stress because of hyperperfusion. Surgical manipulation and/or resection of the collapsed lung may induce lung injury. Re-expansion of the collapsed lung at the conclusion of OLV invariably induces duration-dependent, ischemia-reperfusion injury. Inflammatory cytokines are released in response to localized injury and may promote local and contralateral lung injury. Protective ventilation and volatile anesthesia lessen the degree of injury; however, increases in biochemical and histologic markers of lung injury appear unavoidable. The endothelial glycocalyx may represent a common pathway for lung injury creation during OLV, because it is damaged by most of the recognized lung injurious mechanisms. Experimental therapies to stabilize the endothelial glycocalyx may afford the ability to reduce lung injury in the future. In the interim, protective ventilation with tidal volumes of 4 to 5 mL/kg predicted body weight, positive end-expiratory pressure of 5 to 10 cm H2O, and routine lung recruitment should be used during OLV in an attempt to minimize harmful lung stress and strain. Additional strategies to reduce lung injury include routine volatile anesthesia and efforts to minimize OLV duration and hyperoxia.

  8. Injury to the Developing Lung: experimental and clinic al aspects

    NARCIS (Netherlands)

    I.K.M. Reiss (Irwin)

    2008-01-01

    textabstractInjury to the developing lung or disturbance of normal lung development may lead to a chronic lung disease, bronchopulmonary dysplasia (BPD), which may have long-term effects. BPD is characterized by an arrest of development of the lung and the pulmonary vascular system and occurs in aro

  9. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

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

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

    LENUS (Irish Health Repository)

    Shields, Conor J

    2012-02-03

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

  11. Spontaneous breathing during high-frequency oscillatory ventilation improves regional lung characteristics in experimental lung injury

    NARCIS (Netherlands)

    van Heerde, M.; Roubik, K.; Kopelent, V.; Kneyber, M. C. J.; Markhorst, D. G.

    2010-01-01

    Background Maintenance of spontaneous breathing is advocated in mechanical ventilation. This study evaluates the effect of spontaneous breathing on regional lung characteristics during high-frequency oscillatory (HFO) ventilation in an animal model of mild lung injury. Methods Lung injury was induce

  12. The role of autophagy in lung ischemia/reperfusion injury after lung transplantation in rats

    Science.gov (United States)

    Liu, Sheng; Zhang, Jun; Yu, Bentong; Huang, Lei; Dai, Bin; Liu, Jichun; Tang, Jian

    2016-01-01

    Background: The aim of this study was to explore the role of autophagy in the cold I/R injury following lung transplantation. Methods: The rat orthotopic lung transplantation model was established to perform the level of autophagy in the cold I/R injury in this study. The pretreatment of inhibitor (3-Methyladenine [3-MA]) and activator (rapamycin [RAPA]) of autophagy were performed to assess the role of autophagy in the cold I/R injury following lung transplantation in rats. Results: After lung transplantation, the autophagy, lung cell apoptosis and lung injury were aggravated and peaked at 6 h following the transplantation. The inhibition of autophagy by 3-MA induced downregulated of autophagy, decreased cell apoptosis. Meanwhile, the lung injury, which was indicated by calculating the peak inspiratory pressure (PIP), pulmonary vein blood gas analysis (PO2) and ratio of wet to dry in lung (W/D), was ameliorated after treatment with 3-MA. The activation of autophagy by RAPA causing the upregulated of autophagy and apoptosis of lung cells, and enhanced the lung injury. Conclusion: All the results suggested that the autophagy was involved in the cold I/R injury in lung transplantation model, and played a potential role on the regulation of I/R injury after lung transplantation. PMID:27648150

  13. Pathogenesis of acute lung injury in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  14. Surfactant for pediatric acute lung injury.

    Science.gov (United States)

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

    2008-06-01

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

  15. Traumatic Brain Injury in Rats Induces Lung Injury and Systemic Immune Suppression

    NARCIS (Netherlands)

    Vermeij, Jan-Dirk; Aslami, Hamid; Fluiter, Kees; Roelofs, Joris J.; van den Bergh, Walter M.; Juffermans, Nicole P.; Schultz, Marcus J.; Van der Sluijs, Koen; van de Beek, Diederik; van Westerloo, David J.

    2013-01-01

    Traumatic brain injury (TBI) is frequently complicated by acute lung injury, which is predictive for poor outcome. However, it is unclear whether lung injury develops independently or as a result of mechanical ventilation after TBI. Further, TBI is strongly associated with the development of pneumon

  16. TLR2 deficiency aggravates lung injury caused by mechanical ventilation

    NARCIS (Netherlands)

    Kuipers, Maria Theresa; Jongsma, Geartsje; Hegeman, Maria A; Tuip-de Boer, Anita M; Wolthuis, Esther K; Choi, Goda; Bresser, Paul; van der Poll, Tom; Schultz, Marcus J; Wieland, Catharina W

    2014-01-01

    Innate immunity pathways are found to play an important role in ventilator-induced lung injury. We analyzed pulmonary expression of Toll-like receptor 2 (TLR2) in humans and mice and determined the role of TLR2 in the pathogenesis of ventilator-induced lung injury in mice. Toll-like receptor 2 gene

  17. Soluble ICAM-1 activates lung macrophages and enhances lung injury

    DEFF Research Database (Denmark)

    Schmal, H; Czermak, B J; Lentsch, A B

    1998-01-01

    production of TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of alveolar macrophages to sICAM-1 resulted in NFkappa...... of TNF-alpha and MIP-2 and increased neutrophil recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is intensified lung injury after intrapulmonary disposition of immune complexes.......B activation (which was blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response was also inhibited in the presence...

  18. Finite element modeling of blast lung injury in sheep.

    Science.gov (United States)

    Gibbons, Melissa M; Dang, Xinglai; Adkins, Mark; Powell, Brian; Chan, Philemon

    2015-04-01

    A detailed 3D finite element model (FEM) of the sheep thorax was developed to predict heterogeneous and volumetric lung injury due to blast. A shared node mesh of the sheep thorax was constructed from a computed tomography (CT) scan of a sheep cadaver, and while most material properties were taken from literature, an elastic-plastic material model was used for the ribs based on three-point bending experiments performed on sheep rib specimens. Anesthetized sheep were blasted in an enclosure, and blast overpressure data were collected using the blast test device (BTD), while surface lung injury was quantified during necropsy. Matching blasts were simulated using the sheep thorax FEM. Surface lung injury in the FEM was matched to pathology reports by setting a threshold value of the scalar output termed the strain product (maximum value of the dot product of strain and strain-rate vectors over all simulation time) in the surface elements. Volumetric lung injury was quantified by applying the threshold value to all elements in the model lungs, and a correlation was found between predicted volumetric injury and measured postblast lung weights. All predictions are made for the left and right lungs separately. This work represents a significant step toward the prediction of localized and heterogeneous blast lung injury, as well as volumetric injury, which was not recorded during field testing for sheep.

  19. Transfusion-related acute lung injury.

    Science.gov (United States)

    Federico, Anne

    2009-02-01

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

  20. Acute lung injury induces cardiovascular dysfunction

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  1. ω-3多不饱和脂肪酸在急性肺损伤中的应用进展%Advance in the clinical study of ω-3 polyunsaturated fatty acids on acute lung injury

    Institute of Scientific and Technical Information of China (English)

    章黎

    2011-01-01

    ω-3多不饱和脂肪酸(ω-3 PUFA)为免疫营养中的重要组成部分,具有通过多种分子机制对机体起调控炎症和免疫功能的作用.近年来,发现ω-3 PUFA在急性肺损伤和急性呼吸窘迫综合征治疗中的效果明显.%As one of pharmaconutrients, it has been proven that ω-3 polyunsaturated fatty acids can regulate inflammation and immunological function by different molecular mechanisms. Recently, it has been effectively used in the patients with acute lung injury and acute respiratory distress syndrome. So the progress in application of ω-3 polyunsaturated fatty acids in ALL/ARDS patients is reviewed in this article .

  2. Platelets protect lung from injury induced by systemic inflammatory response

    Science.gov (United States)

    Luo, Shuhua; Wang, Yabo; An, Qi; Chen, Hao; Zhao, Junfei; Zhang, Jie; Meng, Wentong; Du, Lei

    2017-01-01

    Systemic inflammatory responses can severely injure lungs, prompting efforts to explore how to attenuate such injury. Here we explored whether platelets can help attenuate lung injury in mice resulting from extracorporeal circulation (ECC)-induced systemic inflammatory responses. Mice were subjected to ECC for 30 min, then treated with phosphate-buffered saline, platelets, the GPIIb/IIIa inhibitor Tirofiban, or the combination of platelets and Tirofiban. Blood and lung tissues were harvested 60 min later, and lung injury and inflammatory status were assessed. As expected, ECC caused systemic inflammation and pulmonary dysfunction, and platelet transfusion resulted in significantly milder lung injury and higher lung function. It also led to greater numbers of circulating platelet-leukocyte aggregates and greater platelet accumulation in the lung. Platelet transfusion was associated with higher production of transforming growth factor-β and as well as lower levels of tumour necrosis factor-α and neutrophil elastase in plasma and lung. None of these platelet effects was observed in the presence of Tirofiban. Our results suggest that, at least under certain conditions, platelets can protect lung from injury induced by systemic inflammatory responses. PMID:28155889

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

    Science.gov (United States)

    Lee, Jae W

    2009-01-01

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

  4. Oxidative Stress and Lung Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Renata Salatti Ferrari

    2015-01-01

    Full Text Available Ischemia-reperfusion (IR injury is directly related to the formation of reactive oxygen species (ROS, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients.

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

    Science.gov (United States)

    Bruells, C S; Dembinski, R

    2012-04-01

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

  6. 间充质干细胞移植减轻大鼠盐酸吸入性肺损伤%Bone marrow-derived mesenchymal stem cells alleviate lung injury in a rat model of acid aspiration

    Institute of Scientific and Technical Information of China (English)

    吴晓丹; 贾庆安; 钱梦佳; 隆玄; 李善群; 宋元林; 王向东; 白春学

    2013-01-01

    rat model of acid aspiration induced lung injury.Methods BMSCs cultures were obtained from bone marrow of Sprague-Dawley (SD) rats.Twenty-four SD rats were randomly divided into 3 groups:Control,Injury and Injury + BMSCs groups,and hydrochloric acid (HCl) (1.2ml/kg,pH =1.5) or the same volume of phosphate buffered saline (PBS) instead were instilled into trachea of rats to make injury models or for control group respectively.Then,5 × 106 BMSCs or 0.5 ml PBS were injected into jugular vein of rats.Rats were exsanguinated at 6 h after injury.Arterial blood gas,wet/dry ratio and histological changes of lung tissue were determined.Bronchoalveolar lavage fluid (BALF) and serum were collected for the measurement of Tumor necrosis factor-α (TNF-α),Interleukin-6 (IL-6) and Interleukin-10 (IL-10) by Enzyme-linked immuno-sorbent assay (ELISA).In vitro,lung cells from normal rats and from HCl injury rats were co-cultured with BMSCs in a Transwell system (8 μm pore size).Thirty-six hours later,the numbers of migrated BMSCs were counted.In addition,lung cells from HCl injured rats were co-cultured with BMSCs in either a standard single well or in a Transwell (0.4 μm pore size).Control wells were prepared with only lung cells from normal rats or HC; injured rats.After incubation for 6 hours,the cell culture supernalants were then collected to assay the levels of TNF-α,IL-6 and IL-10using ELISA.Comparisons among multiple groups were performed using One-way analysis of variance (ANOVA).Comparisons between groups were carried out using independent-sample t-test.Results BMSCs transplantation attenuated histological lung injury and hypoxia caused by HCl instillation.Injury +BMSCs group decreased wet/dry ratio compared with Injury group.BMSCs administration mediated a down-regulation of inflammation by deceasing TNF-α concentration and increasing IL-10 in BALF and serum.Invitro,co-culture studies of BMSCs with lung cells provided evidence that lung cells stimulated BMSCs migration

  7. Obesity, Inflammation, and Lung Injury (OILI): The Good

    OpenAIRE

    Cheryl Wang

    2014-01-01

    Obesity becomes pandemic, predisposing these individuals to great risk for lung injury. In this review, we focused on the anti-inflammatories and addressed the following aspects: adipocytokines and obesity, inflammation and other mechanisms, adipocytokines and lung injury in obesity bridged by inflammation, and potential therapeutic targets. To sum up, the majority of evidence supported that adiponectin, omentin, and secreted frizzled-related protein 5 (SFRP5) were reduced significantly in ob...

  8. Lung Morphological Changes in Closed Chest Injury (an experimental study

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2012-01-01

    Full Text Available Objective: to study lung morphological changes in a closed chest injury model in laboratory animals. Material and methods. Experiments were carried out in 30 male albino nonbred rats weighing 350—380 g. Closed chest injury was simulated, by exposing the chest of anesthetized rats to a 300-g metal cylinder falling from a height of 30 cm. The observation periods were 1, 3, 6, and 24 hours. Results. The signs of evident perivenular edema that was uncharas-teristic to acute respiratory distress syndrome induced by other causes are an important peculiarity of lung morphological changes in this experimental model of closed chest injury. Conclusion. The experimental studies clarified the pattern of lung morphological changes in the early period after closed chest injury. Key words: closed chest injury, pulmonary edema.

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

    NARCIS (Netherlands)

    R.A. Lachmann

    2006-01-01

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

  10. Lung Injury and Repair In Search of New Treatment Modalities

    NARCIS (Netherlands)

    J. Tibboel (Jeroen)

    2013-01-01

    markdownabstract__Abstract__ The lung contains the largest surface of our body that is exposed to the environment. Day in, day out, our lungs are being exposed to many injurious components, ranging from noxious gasses and particles caused by traffic and chemical industries to a multitude of microor

  11. Therapeutic Strategies for Severe Acute Lung Injury

    Science.gov (United States)

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

    2015-01-01

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

  12. Obesity, Inflammation, and Lung Injury (OILI: The Good

    Directory of Open Access Journals (Sweden)

    Cheryl Wang

    2014-01-01

    Full Text Available Obesity becomes pandemic, predisposing these individuals to great risk for lung injury. In this review, we focused on the anti-inflammatories and addressed the following aspects: adipocytokines and obesity, inflammation and other mechanisms, adipocytokines and lung injury in obesity bridged by inflammation, and potential therapeutic targets. To sum up, the majority of evidence supported that adiponectin, omentin, and secreted frizzled-related protein 5 (SFRP5 were reduced significantly in obesity, which is associated with increased inflammation, indicated by increase of TNFα and IL-6, through activation of toll-like receptor (TLR4 and nuclear factor light chain κB (NF-κB signaling pathways. Administration of these adipocytokines promotes weight loss and reduces inflammation. Zinc-α2-glycoprotein (ZAG, vaspin, IL-10, interleukin-1 receptor antagonist (IL-1RA, transforming growth factor β (TGF-β1, and growth differentiation factor 15 (GDF15 are also regarded as anti-inflammatories. There were controversial reports. Furthermore, there is a huge lack of studies for obesity related lung injury. The effects of adiponectin on lung transplantation, asthma, chronic obstructive pulmonary diseases (COPD, and pneumonia were anti-inflammatory and protective in lung injury. Administration of IL-10 agonist reduces mortality of acute lung injury in rabbits with acute necrotizing pancreatitis, possibly through inhibiting proinflammation and strengthening host immunity. Very limited information is available for other adipocytokines.

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

    Science.gov (United States)

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

    2014-01-01

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

  14. The Field of Tissue Injury in the Lung and Airway

    Science.gov (United States)

    Steiling, Katrina; Ryan, John; Brody, Jerome S.; Spira, Avrum

    2009-01-01

    The concept of field cancerization was first introduced over six decades ago in the setting of oral cancer. Later, field cancerization involving histologic and molecular changes of neoplasms and adjacent tissue began to be characterized in smokers with or without lung cancer. Investigators also described a diffuse, non-neoplastic field of molecular injury throughout the respiratory tract that is attributable to cigarette smoking and susceptibility to smoking-induced lung disease. The potential molecular origins of field cancerization and the field of injury following cigarette smoke exposure in lung and airway epithelia are critical to understanding the impact of the field of injury on clinical diagnostics and therapeutics for smoking-induced lung disease. PMID:19138985

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

    Directory of Open Access Journals (Sweden)

    XiPing Zhang

    2009-01-01

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

  16. Serum and lung endothelin-1 increased in a canine model of ventilator-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    LAI Tian-shun; CAI Shao-xi; GUO Zhen-hui

    2010-01-01

    Background Nitric oxide (NO) plays an important role in acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and in ventilator-induced lung injury (VILI). A change in the balance of endothelin-1 (ET-1) and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model.Methods Models of oleic acid induced ALI were established in dogs; these models were then randomized into three groups undergone different tidal volume (VT) mechanical ventilation, which included a VT6 group (VT equaled to 6 ml/kg body weight, positive end expiratory pressure (PEEP) equaled to 10 cmH_2O, n=6), a VT10 group (VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH_2O, n=4) and a VT20 group (VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH_2O, n=6) for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial.Results PaO_2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALI models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation (P 0.05). There was no significant difference in serum ratio of ET-1/NO between any two out of three groups (P >0.05), although there was a significant positive relationship between serum ET-1 and serum NO (r=0.80, P0.05). In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation (P<0.05) as there was a significant positive relationship between ET-1 and NO in the lung (r=0.54, P<0.05).Conclusions The production of ET-1 and NO

  17. Rabbit model of radiation-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    Zhen-Zong Du; Hua Ren; Jian-Fei Song; Li-Fei Zhang; Feng Lin; Hai-Yong Wang

    2013-01-01

    Objective:To explore the feasibility of establishing an animal model of chronic radiation-induced lung injury.Methods:Twenty-eightNewZealand white rabbits were randomly divided into3 groups(the right lung irradiation group, the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established by high-does radiotherapy in the irradiation groups, then all rabbits underwentCT and pathological examinations at1,2,4,8,12,16 weeks, respectively after radiation.Results:Within4 weeks of irradiation, some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At8-12 weeks after irradiation,CT scanning showed ground glass samples signs, patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

  18. Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury.

    Science.gov (United States)

    Rey-Parra, G J; Vadivel, A; Coltan, L; Hall, A; Eaton, F; Schuster, M; Loibner, H; Penninger, J M; Kassiri, Z; Oudit, G Y; Thébaud, B

    2012-06-01

    Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes α-smooth muscle actin (α-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS.

  19. Lung Injury Induced by High Level of Free Fatty Acids in Rat Model%高游离脂肪酸引起肺损伤的大鼠模型的建立

    Institute of Scientific and Technical Information of China (English)

    高远; 虞敏; 施盛; 金宇飚; 袁忠祥

    2012-01-01

    目的:观察血游离脂肪酸(free fatty acids,FFA)升高对肺组织的损伤及辛伐他汀对此类肺损伤的保护作用.方法:将56只成年雄性SD大鼠随机分为4组,每组14只.4组分别为对照组(不予处理)、高三酰甘油血症组(HTG组)、高游离脂肪酸组(FFA组)、他汀组(实验前给予辛伐他汀,建立高游离脂肪酸模型同FFA组).4组动物模型建立后各取8只采集其血和肺组织,检测血脂(总胆固醇、三酰甘油、FFA)、脂质过氧化指标[丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、血细胞因子[白细胞介素-6(interleukin-6,IL-6),肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),内皮素-1(endothelin-1,ET-1),细胞黏附分子-1(intercellular adhesion module-1,ICAM-1)],并进行动脉血气分析和肺组织病理检查.4组各选取6只大鼠进行伊文思蓝试验,测定肺血管通透性.结果:HTG组、FFA组和他汀组血脂指标均较对照组显著升高,FFA组FFA比HTG组升高2倍以上.FFA组肺损伤明显,表现为血氧分压下降、肺毛细血管通透性升高、肺间质增厚和炎症细胞浸润、肺毛细血管淤血;同时MDA升高,SOD降低,ID6、TNF-α、ET-1和ICAM-1均显著升高.HTG组肺损伤程度较轻,该组除ET-1外,各过氧化指标和细胞因子水平改变均较FFA组小.他汀组血脂水平低于FFA组,血氧、病理、血管通透性、过氧化指标和细胞因子均较FFA组有改善.结论:血FFA升高可能通过脂质过氧化途径和ICAM-1途径引起肺损伤,辛伐他汀对此有保护作用.%Objective:To build a rat model of lung injury induced by high level of free fatty acids (FFA),and to investigate the protective effect of Simvastatin. Methods: A total of 56 male adult Sprague-Dawley rats were divided into four groups: the control group,HTG group (hypertriglyceridemia model),FFA group (high FFA model) and Statin group (rats were treated with simvastatin before they were injected with

  20. Smoking water pipe is injurious to lungs

    DEFF Research Database (Denmark)

    Sivapalan, Pradeesh; Ringbæk, Thomas; Lange, Peter

    2014-01-01

    This review describes the pulmonary consequences of water pipe smoking. Smoking water pipe affects the lung function negatively, is significantly associated with chronic obstructive pulmonary disease and increases the risk of lung infections. Case reports suggest that regular smokers of water pipe...

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

    Directory of Open Access Journals (Sweden)

    Ewan Christopher Goligher

    2009-01-01

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

  2. The Field of Tissue Injury in the Lung and Airway

    OpenAIRE

    Steiling, Katrina; Ryan, John; Brody, Jerome S.; Spira, Avrum

    2008-01-01

    The concept of field cancerization was first introduced over six decades ago in the setting of oral cancer. Later, field cancerization involving histologic and molecular changes of neoplasms and adjacent tissue began to be characterized in smokers with or without lung cancer. Investigators also described a diffuse, non-neoplastic field of molecular injury throughout the respiratory tract that is attributable to cigarette smoking and susceptibility to smoking-induced lung disease. The potentia...

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Prevention of reperfusion lung injury by lidocaine in isolated rat lung ventilated with higher oxygen levels.

    Directory of Open Access Journals (Sweden)

    Das K

    2003-01-01

    Full Text Available BACKGROUND: Lidocaine, an antiarrhythmic drug has been shown to be effective against post-ischaemic reperfusion injury in heart. However, its effect on pulmonary reperfusion injury has not been investigated. AIMS: We investigated the effects of lidocaine on a postischaemic reperfused rat lung model. MATERIALS AND METHODS: Lungs were isolated and perfused at constant flow with Krebs-Henseilet buffer containing 4% bovine serum albumin, and ventilated with 95% oxygen mixed with 5% CO2. Lungs were subjected to ischaemia by stopping perfusion for 60 minutes followed by reperfusion for 10 minutes. Ischaemia was induced in normothermic conditions. RESULTS: Postischaemic reperfusion caused significant (p < 0.0001 higher wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure compared to control lungs. Lidocaine, at a dose of 5mg/Kg b.w. was found to significantly (p < 0.0001 attenuate the increase in the wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure observed in post-ischaemic lungs. CONCLUSION: Lidocaine is effective in preventing post-ischaemic reperfusion injury in isolated, perfused rat lung.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  6. Sports-related lung injury during breath-hold diving

    Directory of Open Access Journals (Sweden)

    Tanja Mijacika

    2016-12-01

    Full Text Available The number of people practising recreational breath-hold diving is constantly growing, thereby increasing the need for knowledge of the acute and chronic effects such a sport could have on the health of participants. Breath-hold diving is potentially dangerous, mainly because of associated extreme environmental factors such as increased hydrostatic pressure, hypoxia, hypercapnia, hypothermia and strenuous exercise. In this article we focus on the effects of breath-hold diving on pulmonary function. Respiratory symptoms have been reported in almost 25% of breath-hold divers after repetitive diving sessions. Acutely, repetitive breath-hold diving may result in increased transpulmonary capillary pressure, leading to noncardiogenic oedema and/or alveolar haemorrhage. Furthermore, during a breath-hold dive, the chest and lungs are compressed by the increasing pressure of water. Rapid changes in lung air volume during descent or ascent can result in a lung injury known as pulmonary barotrauma. Factors that may influence individual susceptibility to breath-hold diving-induced lung injury range from underlying pulmonary or cardiac dysfunction to genetic predisposition. According to the available data, breath-holding does not result in chronic lung injury. However, studies of large populations of breath-hold divers are necessary to firmly exclude long-term lung damage.

  7. Sports-related lung injury during breath-hold diving.

    Science.gov (United States)

    Mijacika, Tanja; Dujic, Zeljko

    2016-12-01

    The number of people practising recreational breath-hold diving is constantly growing, thereby increasing the need for knowledge of the acute and chronic effects such a sport could have on the health of participants. Breath-hold diving is potentially dangerous, mainly because of associated extreme environmental factors such as increased hydrostatic pressure, hypoxia, hypercapnia, hypothermia and strenuous exercise.In this article we focus on the effects of breath-hold diving on pulmonary function. Respiratory symptoms have been reported in almost 25% of breath-hold divers after repetitive diving sessions. Acutely, repetitive breath-hold diving may result in increased transpulmonary capillary pressure, leading to noncardiogenic oedema and/or alveolar haemorrhage. Furthermore, during a breath-hold dive, the chest and lungs are compressed by the increasing pressure of water. Rapid changes in lung air volume during descent or ascent can result in a lung injury known as pulmonary barotrauma. Factors that may influence individual susceptibility to breath-hold diving-induced lung injury range from underlying pulmonary or cardiac dysfunction to genetic predisposition.According to the available data, breath-holding does not result in chronic lung injury. However, studies of large populations of breath-hold divers are necessary to firmly exclude long-term lung damage.

  8. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E;

    2011-01-01

    of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report.......A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...

  9. Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury

    OpenAIRE

    2008-01-01

    BACKGROUND: Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and c-Jun-NH(2)-terminal kinase-1 in ventilator-induced lung injury and investigate novel independent mechanisms contributing to lung injury during ...

  10. Effects of remifentanil on acute lung injury induced by oleic acid in rabbits%瑞芬太尼对兔油酸性急性肺损伤的影响

    Institute of Scientific and Technical Information of China (English)

    杜成; 孙思庆; 王润丰; 徐婷

    2015-01-01

    Objective:To investigate the effects of remifentanil ( RF) on acute lung injury( ALI) induced by oleic acid in rabbits. Methods:Eighteen healthy male New Zealand white rabbits weighing 2. 5-3. 5 kg were randomly divided into 3 groups ( n=6 each):control group, oleic acid group and RF group. The animals were anesthetized with intravenous 3% pentobarbital sodium 30 mg·kg-1 , tracheostomized and mechanically ventilated. The carotid artery and jugular vein were cannulated for blood sampling, fluid and drug administration. Oleic acid 0. 1 ml·kg-1 in 10 ml of normal saline (NS) was infused over 30 min in oleic acid group and RF group. RF 0. 2 μg·kg-1· min-1 was infused starting from 15 min before oleic acid administration until the death of the animals. PaO2 and plasma ICAM-1,TNF-αand IL-8 concentration were measured immediately before oleic acid infusion and at 6 h after the end of oleic acid infusion. The animals were killed and the lungs were immediately removed for microscopic examination and determination of W/D lung weight ratio. Results: PaO2 were significantly decreased while W/D ratio were significantly increased in oleic group and RF group as compared with control group. Oleic acid significantly increased plasma ICAM-1,TNF-αand IL-8 concentration and damaged the structure of lung tissue. Remifentanil infusion significantly attenuated the OA-induced changes in a dose-dependent manner. Conclusion:RF has protective effect against acute lung injury induced by oleic acid and inhibition of ICAM-1,TNF-αand IL-8 expression is involved in the mechanism.%目的::探讨瑞芬太尼对兔油酸性急性肺损伤( ALI )的影响。方法:选取健康成年雄性新西兰大白兔18只,由东南大学医学院实验动物中心提供,体质量2.5~3.5 kg,随机分为3组(n=6),即对照组、油酸组和瑞芬太尼组。对照组经30 min静脉输注生理盐水10 ml;油酸组经30 min静脉注射油酸0.1 ml·kg-1;瑞芬太尼组静脉输注瑞芬太尼0.2

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

    Directory of Open Access Journals (Sweden)

    Di Nardo Matteo

    2008-06-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Duan Yingli

    2012-01-01

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

  14. Tissue plasminogen activator attenuates ventilatorinduced lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liang-ti HUANG; Hsiu-chu CHOU; Leng-fang WANG; Chung-ming CHEN

    2012-01-01

    Aim:To test the hypothesis that the tissue plasminogen activator (tPA) may counteract the inhibitory effect ot plasminogen activator inhibitors (PAI) and attenuate lung injury in a rat model of ventilator-induced lung injury (VILI).Methods:Adult male Sprague-Dawley rats were ventilated with a HVZP (high-volume zero PEEP) protocol for 2 h at a tidal volume of 30 ml/kg,a respiratory rate of 25 breaths/min,and an inspired oxygen fraction of 21%.The rats were divided into 3 groups (n=7 for each):HVZP+tPA group receiving tPA (1.25 mg/kg,iv) 15 min before ventilation,HVZP group receiving HVZP+vehicle injection,and a control group receiving no ventilation.After 2 h of ventilation,the rats were killed; blood and lungs were collected for biochemical and histological analyses.Results:HVZP ventilation significantly increased total protein content and the concentration of macrophage inflammatory protein-2 (MIP-2) in the bronchoalveolar lavage fluid (BALF) as well as the lung injury score.Rats that received HVZP ventilation had significantly higher lung PAI-1 mRNA expression,plasma PAI-1and plasma D-dimer levels than the control animals,tPA treatment significantly reduced the BALF total protein and the lung injury score as compared to the HVZP group,tPA treatment also significantly decreased the plasma D-dimer levels and the HVZP ventilation-induced lung vascular fibrin thrombi,tPA treatment showed no effect on MIP-2 level in BALF.Conclusion:These results demonstrate that VILI increases lung PAI-1 mRNA expression,plasma levels of PAI-1 and D-limers,lung injury score and vascular fibrin deposition,tPA can attenuate VILI by decreasing capillary-alveolar protein leakage as well as local and systemic coagulation as shown by decreased lung vascular fibrin deposition and plasma D-dimers.

  15. Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Bhargava, Maneesh; Viken, Kevin J; Dey, Sanjoy; Steinbach, Michael S; Wu, Baolin; Jagtap, Pratik D; Higgins, LeeAnn; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel J; Kumar, Vipin; Arora, Mukta; Bitterman, Peter B; Ingbar, David H; Wendt, Chris H

    2016-08-01

    Pulmonary complications due to infection and idiopathic pneumonia syndrome (IPS), a noninfectious lung injury in hematopoietic stem cell transplant (HSCT) recipients, are frequent causes of transplantation-related mortality and morbidity. Our objective was to characterize the global bronchoalveolar lavage fluid (BALF) protein expression of IPS to identify proteins and pathways that differentiate IPS from infectious lung injury after HSCT. We studied 30 BALF samples from patients who developed lung injury within 180 days of HSCT or cellular therapy transfusion (natural killer cell transfusion). Adult subjects were classified as having IPS or infectious lung injury by the criteria outlined in the 2011 American Thoracic Society statement. BALF was depleted of hemoglobin and 14 high-abundance proteins, treated with trypsin, and labeled with isobaric tagging for relative and absolute quantification (iTRAQ) 8-plex reagent for two-dimensional capillary liquid chromatography (LC) and data dependent peptide tandem mass spectrometry (MS) on an Orbitrap Velos system in higher-energy collision-induced dissociation activation mode. Protein identification employed a target-decoy strategy using ProteinPilot within Galaxy P. The relative protein abundance was determined with reference to a global internal standard consisting of pooled BALF from patients with respiratory failure and no history of HSCT. A variance weighted t-test controlling for a false discovery rate of ≤5% was used to identify proteins that showed differential expression between IPS and infectious lung injury. The biological relevance of these proteins was determined by using gene ontology enrichment analysis and Ingenuity Pathway Analysis. We characterized 12 IPS and 18 infectious lung injury BALF samples. In the 5 iTRAQ LC-MS/MS experiments 845, 735, 532, 615, and 594 proteins were identified for a total of 1125 unique proteins and 368 common proteins across all 5 LC-MS/MS experiments. When comparing IPS to

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  17. Reducing ventilator-induced lung injury and other organ injury by the prone position

    Science.gov (United States)

    Suter, Peter M

    2006-01-01

    Mechanical ventilation can cause structural and functional disturbances in the lung, as well as other vital organ dysfunctions. Apoptosis is thought to be a histological sign of distant organ damage in ventilator-induced lung injury (VILI). Nakos and colleagues observed a protective effect of prone positioning against VILI in normal sheep. Less alteration in the lung architecture and function and in liver transaminases, and lower indices for apoptosis in the liver, the diaphragm and the lung were noted in the prone position compared with the supine position. If confirmed, these data open a new hypothesis for pathogenesis and prevention of VILI and its extrapulmonary complications. PMID:16677405

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    徐涛; 曾邦雄; 李兴旺

    2004-01-01

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

  20. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E;

    2011-01-01

    of acute rejection, worsened within 2 weeks, despite high-dose steroids, change of calcineurin inhibitor, and plasmapheresis. Within a few days after a single, 10-mg, intravenous dose of alemtuzumab, the patient's health improved markedly. She has remained stable for 4 months on a standard, ambulatory......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  1. ERYTHROMYCIN POLYLACTIC ACID MICROSPHERES FOR LUNG TARGETING

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    AIM: To prepare polylactic acid microspheres of Erythromycin for Lung targeting.METHEDS: The orthogonal test design was used to optimize the technology,of preparation. Thecharacter of the microspheres, drug release in vitro, stability and tissue distribution were examinedRESULTS: The Erythromycin polylactic acid microspheres was regular in its morphology. Drugwas enveloped in microspheres but not physically mixed with PDLLA. The average particle size was11.65μn with over 94% of the microspheres being in the range of 5~20trn; The drug loading andthe incorporation efciency were 18% and 60% respectively. The microspheres were stable for threemonth at 4 ℃ and room temperature. The in vitro release properties could be expressed by theHiguchi's equation: y = 28.067 + 3.8515t11/2 (r = 0.9834). Comparing with injection, the drug inmicrospheres was more concentrated in lung tissue. CONCLUSION: Erythromycin polylactic acidmicrospheres showed significant sustained release and lung targeting.

  2. Differing patterns of P-selectin expression in lung injury

    DEFF Research Database (Denmark)

    Bless, N M; Tojo, S J; Kawarai, H

    1998-01-01

    Using two models of acute lung inflammatory injury in rats (intrapulmonary deposition of immunoglobulin G immune complexes and systemic activation of complement after infusion of purified cobra venom factor), we have analyzed the requirements and patterns for upregulation of lung vascular P......-selectin. In the immune complex model, upregulation of P-selectin was defined by Northern and Western blot analysis of lung homogenates, by immunostaining of lung tissue, and by vascular fixation of 125I-labeled anti-P-selectin. P-selectin protein was detected by 1 hour (long before detection of mRNA) and expression......-selectin was dependent on an intact complement system, and the presence of blood neutrophils was susceptible to the antioxidant dimethyl sulfoxide and required C5a but not tumor necrosis factor alpha. In contrast, in the cobra venom factor model, upregulation of P-selectin, which is C5a dependent, was also dimethyl...

  3. Ozone therapy ameliorates paraquat-induced lung injury in rats.

    Science.gov (United States)

    Kaldirim, Umit; Uysal, Bulent; Yuksel, Ramazan; Macit, Enis; Eyi, Yusuf E; Toygar, Mehmet; Tuncer, Salim K; Ardic, Sukru; Arziman, Ibrahim; Aydin, Ibrahim; Oztas, Yesim; Karslioglu, Yildirim; Topal, Turgut

    2014-12-01

    Paraquat (PQ) overdose can cause acute lung injury and death. Ozone therapy (OT) was previously demonstrated to alleviate inflammation and necrosis in various pathologies. We therefore hypothesized that OT has ameliorative and preventive effects on PQ-induced lung damage due to anti-inflammatory and antioxidants properties. Sprague-Dawley rats (n = 24) were separated into three groups: sham, PQ, and PQ+OT groups. 15 mg/kg PQ was administered intraperitoneally in PQ and PQ+OT groups to induce experimental lung injury. One hour after PQ treatment, PQ+OT group was administered a single dose of ozone-oxygen mixture (1 mg/kg/day) by intraperitoneal route for four consecutive days. The animals were sacrificed on fifth day after PQ administration. Blood samples and lung tissues were collected to evaluate the inflammatory processes, antioxidant defense and pulmonary damage. Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, total TGF-β1 levels, and histological injury scores in PQ+OT group were significantly lower than PQ group (Ptherapy.

  4. Strategies to prevent intraoperative lung injury during cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Siminelakis Stavros N

    2010-01-01

    Full Text Available Abstract During open heart surgery the influence of a series of factors such as cardiopulmonary bypass (CPB, hypothermia, operation and anaesthesia, as well as medication and transfusion can cause a diffuse trauma in the lungs. This injury leads mostly to a postoperative interstitial pulmonary oedema and abnormal gas exchange. Substantial improvements in all of the above mentioned factors may lead to a better lung function postoperatively. By avoiding CPB, reducing its time, or by minimizing the extracorporeal surface area with the use of miniaturized circuits of CPB, beneficial effects on lung function are reported. In addition, replacement of circuit surface with biocompatible surfaces like heparin-coated, and material-independent sources of blood activation, a better postoperative lung function is observed. Meticulous myocardial protection by using hypothermia and cardioplegia methods during ischemia and reperfusion remain one of the cornerstones of postoperative lung function. The partial restoration of pulmonary artery perfusion during CPB possibly contributes to prevent pulmonary ischemia and lung dysfunction. Using medication such as corticosteroids and aprotinin, which protect the lungs during CPB, and leukocyte depletion filters for operations expected to exceed 90 minutes in CPB-time appear to be protective against the toxic impact of CPB in the lungs. The newer methods of ultrafiltration used to scavenge pro-inflammatory factors seem to be protective for the lung function. In a similar way, reducing the use of cardiotomy suction device, as well as the contact-time between free blood and pericardium, it is expected that the postoperative lung function will be improved.

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

    Directory of Open Access Journals (Sweden)

    Xianming Zhang

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

  6. Protective effects of asiaticoside on septic lung injury in mice.

    Science.gov (United States)

    Zhang, Li-na; Zheng, Jia-jia; Zhang, Li; Gong, Xia; Huang, Hai; Wang, Chang-dong; Wang, Bin; Wu, Meng-jiao; Li, Xiao-hui; Sun, Wen-juan; Liu, Ying-ju; Wan, Jing-yuan

    2011-09-01

    Asiaticoside (AS), a major triterpenoid saponin component isolated from Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities. The present study aimed to determine the protective effects and the underlying mechanisms of AS on septic lung injury induced by cecal ligation and puncture (CLP). Mice were pretreated with the AS (45 mg/kg) or AS as well as GW9662 at 1h before CLP, the survival, lung injury, inflammatory mediators and signaling molecules, and Peroxisome proliferator-activated receptor-γ (PPAR-γ) were determined 24 h after CLP. The results showed that AS significantly decreased CLP-induced the mortality, lung pathological damage, the infiltration of mononuclear, polymorphonuclear (PMN) leucocytes and total proteins. Moreover, AS inhibited CLP-induced the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB), the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein in lung tissues, and the production of serum tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Interestingly, the expression of PPAR-γ protein in lung tissue was up-regulated by AS. Furthermore, GW9662 (the inhibitor of PPAR-γ) significantly reversed these beneficial effects of AS in septic mice. These findings suggest that AS could effectively protect from septic lung injury induced by CLP and the underlying mechanisms might be related to up-regulation of PPAR-γ expression to some extent, which inhibits MAPKs and NF-κB pathway.

  7. Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism.

    Science.gov (United States)

    Fletcher, Marianne E; Boshier, Piers R; Wakabayashi, Kenji; Keun, Hector C; Smolenski, Ryszard T; Kirkham, Paul A; Adcock, Ian M; Barton, Paul J; Takata, Masao; Marczin, Nandor

    2015-06-15

    Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-π but not GST-μ expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD(+)/NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-π, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications.

  8. ω-3多不饱和脂肪酸治疗急性肺损伤的Meta分析%Impact of omega-3 fatty acids supplementation in acute lung injury patients: a Meta-analysis of randomized controlled trials

    Institute of Scientific and Technical Information of China (English)

    田宏亮; 田红岩; 韦丽娜; 段磊; 孔玉科; 曾嵘

    2012-01-01

    To evaluate the impact of omega-3 fatty acids intervention on clinical outcomes in acute lung injury patients. Methods: Literatures relating to the evaluation of the omega-3 fatty acids in acute lung injury patients were searched in databases including PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Databases , China National Knowledge Infrastructure, and Wanfang Database etc. All the eligible studies were randomized controlled trials and their results were published up to October 2012. The quality of the included studies was evaluated by Jadad evaluation standard. The data were analyzed with RevMan 5. 1 from the Cochrane Collaboration. Results: Totally 6 randomized controlled trials entered final meta analysis study and the baseline data of each trial were comparable. The results showed a significant effectiveness in the PaO2, PaO2/FiO2,Total Protein,LOS. However, the length of LOV stay and adverse effects showed no significant difference between two group. Conclusion: Omega-3 fatty acids interventions can benefit patients by reducing the morbidity of postoperative infectious complications and shortening the length of hospital stay.%目的:探讨ω-3多不饱和脂肪酸(ω-3PUFA)治疗急性肺损伤(ALI)病人的临床效果及其应用价值.方法:计算机检索PubMed、EMBASE、SCI、Cochrane Library、中国生物医学文献数据库、中文科技期刊全文数据库、中国期刊全文数据库和中华医学会数字化期刊,并辅助手工检索,收集采用ω-3PUFA治疗ALI的随机对照试验(RCT),检索至2012年10月截止.采用Jadad评分评价纳入研究质量,用RevMan 5.1软件进行Meta分析.结果:共纳入6个RCT,各试验间资料均有可比性.经Meta分析结果显示,试验组(ω-3PUFA治疗组)与对照组(常规治疗组)在ALI病人的动脉氧分压(PaO2)、氧合指数(PaO2/FiO2)、入住ICU时间(LOS)和总蛋白(TP)等方面均有显著性差异,而撤离呼吸机时间(LOV)和不良反应则

  9. Estabilidade do modelo animal de lesão pulmonar aguda induzida por ácido oleico Stability of the animal model of oleic acid-induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Eduardo Gaio

    2009-08-01

    Full Text Available OBJETIVO: Avaliar a estabilidade das variáveis hemodinâmicas, da mecânica respiratória e de troca gasosa do modelo animal de lesão pulmonar aguda induzida por ácido oleico. MÉTODOS: Trata-se de um estudo experimental no qual foram utilizados 10 cães de raça indeterminada. As variáveis foram aferidas inicialmente e em 30, 60, 90 e 120 min após a administração do ácido oleico. Para analisar as medidas repetidas, foram testados efeitos lineares e quadráticos e foram utilizados ajustes de modelos lineares mistos com estruturas de variâncias e covariâncias diversificadas, dependendo da variável analisada. RESULTADOS: Observamos estabilidade da pressão arterial média aos 30 min, assim como da frequência cardíaca, da pressão arterial pulmonar e da pressão de capilar pulmonar aos 60 min. Frequência respiratória, volume corrente, volume minuto e trabalho respiratório estabilizaram aos 30 min. Quanto às variáveis de troca gasosa, PaO2, relação PaO2/FiO2 e fração de shunt pulmonar estabilizaram-se aos 30 min. As demais variáveis mantiveram-se em ascensão ou queda contínuas. CONCLUSÕES: O modelo de lesão pulmonar aguda induzida por ácido oleico é estável para algumas das variáveis testadas; porém, a estabilização se dá em momentos diferentes. As variáveis da mecânica respiratória e de troca gasosa estabilizaram em 30 min, e as hemodinâmicas, em 60 min.OBJECTIVE: To evaluate the stability of hemodynamic, respiratory and gas exchange variables in an animal model of oleic acid-induced acute lung injury. METHODS: This was an experimental study involving 10 mongrel dogs. The variables were measured at baseline, as well as at 30, 60, 90 and 120 min after the administration of oleic acid. In order to analyze repeated measurements, linear and quadratic effects were tested. Mixed linear models with diversified variance and covariance structures were used, depending on the variable studied. RESULTS: We found that mean

  10. Cotton dust-mediated lung epithelial injury.

    OpenAIRE

    Ayars, G H; Altman, L C; O'Neil, C E; Butcher, B T; Chi, E Y

    1986-01-01

    To determine if constituents of cotton plants might play a role in byssinosis by injuring pulmonary epithelium, we added extracts of cotton dust, green bract, and field-dried bract to human A549 and rat type II pneumocytes. Injury was measured as pneumocyte lysis and detachment, and inhibition of protein synthesis. Extracts of cotton dust and field-dried bract produced significant dose- and time-dependent lysis and detachment of both target cells, while green bract extract was less damaging. ...

  11. Chorioamnionitis and Lung Injury in Preterm Newborns

    Directory of Open Access Journals (Sweden)

    Gustavo Rocha

    2013-01-01

    Full Text Available There is a strong evidence that histologic chorioamnionitis is associated with a reduction of incidence and severity of respiratory distress syndrome (RDS. Short-term maturational effects on the lungs of extremely premature infants seem to be, however, accompanied by a greater susceptibility of the lung, eventually contributing to an increased risk of bronchopulmonary dysplasia (BPD. Genetic susceptibility to BPD is an evolving area of research and several studies have directly related the risk of BPD to genomic variants. There is a substantial heterogeneity across the studies in the magnitude of the association between chorioamnionitis and BPD, and whether or not the association is statistically significant. Considerable variation is largely dependent on differences of inclusion and exclusion criteria, as well as on clinical and histopathological definitions. The presence of significant publication bias may exaggerate the magnitude of the association. Controlling for publication bias may conduct to adjusted results that are no longer significant. Recent studies generally seem to confirm the effect of chorioamnionitis on RDS incidence, while no effect on BPD is seen. Recent data suggest susceptibility for subsequent asthma to be increased on long-term followup. Additional research on this field is needed.

  12. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    Science.gov (United States)

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2015-12-04

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  13. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

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

    1995-01-01

    injury. In the current study, we sought to determine whether endogenous IL-10 is playing a regulatory role in the lung inflammatory response. On the basis of lung mRNA and ELISA measurements, IL-10 induction was found during development of inflammation in the IgG immune complex model of lung injury...

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

    Science.gov (United States)

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

    2014-10-01

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

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

    Science.gov (United States)

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

    2009-06-01

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

  16. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  17. ERYTHROMYCIN POLYLACTIC ACID MICROSPHERES FOR LUNG TARGETING

    Institute of Scientific and Technical Information of China (English)

    YANGFan; YANBing; 等

    2002-01-01

    AIM:To prepare polylactiv acid microspheres of Erythromycin for Lung targeting.METHEDS:The orthogonal test design was used to optimize the technology of preparation.The character of the microspheres,drug release in vitro,stabiligy and tissue distribution were examined. RESULTS:The Erythromycin polylatic acid microspheres was regular in its morphology.Drug was enveloped in microspheres but not physically mixed with PDLLA.The average particle size was 11.65μm with over 94% of the microspheres being in the range of 5-20μm;The drug loading and the incorporation efficiency were 18% and 60% respectively.The microspheres were stable for three month at 4℃ and room temperature.The in vitro release properties could be expressed by the Higuchi′s equation:y=28.067+3.8515t1/2(r=0.9834).Comparing with injection,the drug in microspheres was more concentrated in lung tissue.CONLUSION:Erythromycin polylactic acid microspheres showed significant sustained release and lung targeting.

  18. Lung contusion: inflammatory mechanisms and interaction with other injuries.

    Science.gov (United States)

    Raghavendran, Krishnan; Notter, Robert H; Davidson, Bruce A; Helinski, Jadwiga D; Kunkel, Steven L; Knight, Paul R

    2009-08-01

    This article reviews current animal models and laboratory studies investigating the pathophysiology of lung contusion (LC), a common and severe condition in patients with blunt thoracic trauma. Emphasis is on studies elucidating cells, mediators, receptors, and processes important in the innate pulmonary inflammatory response that contribute to LC injury. Surfactant dysfunction in the pathogenesis of LC is also discussed, as is the potential role of epithelial cell or neutrophil apoptosis. Studies examining combination injuries where LC is exacerbated by secondary insults such as gastric aspiration in trauma patients are also noted. The need for continuing mechanism-based research to further clarify the pathophysiology of LC injury, and to define and test potential therapeutic interventions targeting specific aspects of inflammation or surfactant dysfunction to improve clinical outcomes in patients with LC, is also emphasized.

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

    Science.gov (United States)

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

    2015-02-01

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

  20. Lung function

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

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

  1. Nicotinamide exacerbates hypoxemia in ventilator-induced lung injury independent of neutrophil infiltration.

    Directory of Open Access Journals (Sweden)

    Heather D Jones

    Full Text Available Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3 directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury.We administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε.Nicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice.Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but paradoxically also leads to the

  2. Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

    Science.gov (United States)

    Jones, Heather D.; Yoo, Jeena; Crother, Timothy R.; Kyme, Pierre; Ben-Shlomo, Anat; Khalafi, Ramtin; Tseng, Ching W.; Parks, William C.; Arditi, Moshe

    2015-01-01

    Background Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3) directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury. Methods We administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε. Results Nicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice. Conclusions Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but

  3. Bile-acid-induced cell injury and protection

    Institute of Scientific and Technical Information of China (English)

    Maria J Perez; Oscar Briz

    2009-01-01

    Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids (BAs) in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyl-Nmethylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties.

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

    Science.gov (United States)

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

    2006-05-01

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

  5. Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Tamás Dolinay

    Full Text Available BACKGROUND: Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and c-Jun-NH(2-terminal kinase-1 in ventilator-induced lung injury and investigate novel independent mechanisms contributing to lung injury during mechanical ventilation. METHODOLOGY AND PRINCIPLE FINDINGS: C57/BL6 wild-type mice and mice genetically deleted for mitogen-activated protein kinase kinase-3 (mkk-3(-/- or c-Jun-NH(2-terminal kinase-1 (jnk1(-/- were ventilated, and lung injury parameters were assessed. We demonstrate that mkk3(-/- or jnk1(-/- mice displayed significantly reduced inflammatory lung injury and apoptosis relative to wild-type mice. Since jnk1(-/- mice were highly resistant to ventilator-induced lung injury, we performed comprehensive gene expression profiling of ventilated wild-type or jnk1(-/- mice to identify novel candidate genes which may play critical roles in the pathogenesis of ventilator-induced lung injury. Microarray analysis revealed many novel genes differentially expressed by ventilation including matrix metalloproteinase-8 (MMP8 and GADD45alpha. Functional characterization of MMP8 revealed that mmp8(-/- mice were sensitized to ventilator-induced lung injury with increased lung vascular permeability. CONCLUSIONS: We demonstrate that mitogen-activated protein kinase pathways mediate inflammatory lung injury during ventilator-induced lung injury. C-Jun-NH(2-terminal kinase was also involved in alveolo-capillary leakage and edema formation, whereas MMP8 inhibited alveolo-capillary protein leakage.

  6. I-FABP as biomarker for the early diagnosis of acute mesenteric ischemia and resultant lung injury.

    Directory of Open Access Journals (Sweden)

    Rachel G Khadaroo

    Full Text Available Acute mesenteric ischemia (AMI is a life-threatening condition that can result in multiple organ injury and death. A timely diagnosis and treatment would have a significant impact on the morbidity and mortality in high-risk patient population. The purpose of this study was to investigate if intestinal fatty acid binding protein (I-FABP and α-defensins can be used as biomarkers for early AMI and resultant lung injury. C57BL/6 mice were subjected to intestinal ischemia by occlusion of the superior mesenteric artery. A time course of intestinal ischemia from 0.5 to 3 h was performed and followed by reperfusion for 2 h. Additional mice were treated with N-acetyl-cysteine (NAC at 300 mg/kg given intraperitoneally prior to reperfusion. AMI resulted in severe intestinal injury characterized by neutrophil infiltrate, myeloperoxidase (MPO levels, cytokine/chemokine levels, and tissue histopathology. Pathologic signs of ischemia were evident at 1 h, and by 3 h of ischemia, the full thickness of the intestine mucosa had areas of coagulative necrosis. It was noted that the levels of α-defensins in intestinal tissue peaked at 1 h and I-FABP in plasma peaked at 3 h after AMI. Intestinal ischemia also resulted in lung injury in a time-dependent manner. Pretreatment with NAC decreased the levels of intestinal α-defensins and plasma I-FABP, as well as lung MPO and cytokines. In summary, the concentrations of intestinal α-defensins and plasma I-FABP predicted intestinal ischemia prior to pathological evidence of ischemia and I-FABP directly correlated with resultant lung injury. The antioxidant NAC reduced intestinal and lung injury induced by AMI, suggesting a role for oxidants in the mechanism for distant organ injury. I-FABP and α-defensins are promising biomarkers, and may guide the treatment with antioxidant in early intestinal and distal organ injury.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  9. Melatonin reduces acute lung injury in endotoxemic rats

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  10. Stressed lungs: unveiling the role of circulating stress hormones in ozone-induced lung injury and inflammation.

    Science.gov (United States)

    Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction ...

  11. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury.

    Science.gov (United States)

    Imai, Yumiko; Kuba, Keiji; Neely, G Greg; Yaghubian-Malhami, Rubina; Perkmann, Thomas; van Loo, Geert; Ermolaeva, Maria; Veldhuizen, Ruud; Leung, Y H Connie; Wang, Hongliang; Liu, Haolin; Sun, Yang; Pasparakis, Manolis; Kopf, Manfred; Mech, Christin; Bavari, Sina; Peiris, J S Malik; Slutsky, Arthur S; Akira, Shizuo; Hultqvist, Malin; Holmdahl, Rikard; Nicholls, John; Jiang, Chengyu; Binder, Christoph J; Penninger, Josef M

    2008-04-18

    Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.

  12. Histomorphologic change of radiation pneumonitis in rat lungs: captopril reduces rat lung injury induced by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Hee [College of Medicine, Keimhyung Univ., Taegu (Korea, Republic of)

    1999-09-01

    To assess the histomorphologic changes in the rat lung injury induced by radiation, to determine whether captopril reduces the rat lung injury and to evaluate change in TNF-{alpha} and TGF {beta} and rat lung damage by radiation and captopril. Right lungs in male Sprague-Dawley rats were divided irradiation alone (10, 20, 30 Gy) or radiation (same dose with radiation alone group) with captopril (500 mg/L). Radiation alone group were sacrificed at twelve hours and eleven weeks after radiation and radiation with captopril group (captopril group) were sacrificed at eleven weeks after radiation with captopril. We examined the light microscope and electron microscopic features in the groups. In radiation alone group, there were patch parenchymal collapse and consolidation at twelve hours after radiation. The increase of radiation dose shows more prominent the severity and broader the affected areas. Eleven weeks after radiation, the severity and areas of fibrosis had increased in proportion to radiation dose given in the radiation alone group. There was notable decrease of lung fibrosis in captopril group than in radiation alone group. The number of mast cells rapidly increased with increase of radiation dose in radiation alone group and the degree of increase of mast cell number and severity of collagen accumulation more decreased in captopril group than in radiation alone group. In radiation alone group expression of TNF-{alpha} and TGF-{beta}] increased according to increase of radiation dose at twelve hours after radiation in both group. At eleven weeks after radiation, expression of TGF- P increased according to increase of radiation dose in radiation group but somewhat decreased in captopril group. In the captopril group the collagen deposition increased but less dense than those of radiation alone group. The severity of perivascular thickening, capillary change, the number and degranulation of mast cells more decreased in the captopril group than in the radiation

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

    OpenAIRE

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

    2013-01-01

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

  14. ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin

    NARCIS (Netherlands)

    R.M. Wösten-van Asperen; R. Lutter (Rene); J.J. Haitsma; M.P. Merkus; J.B. van Woensel; C.M. van der Loos; S. Florquin (Sandrine); B.F. Lachmann (Burkhard); A.P. Bos (Albert)

    2008-01-01

    textabstractVentilator-induced lung injury is characterised by inflammation and apoptosis, but the underlying mechanisms are poorly understood. The present study proposed a role for angiotensin-converting enzyme (ACE) via angiotensin II (Ang II) and/or bradykinin in acute lung injury. The authors as

  15. Mitochondrial biogenesis in the pulmonary vasculature during inhalation lung injury and fibrosis

    Science.gov (United States)

    Cell survival and injury repair is facilitated by mitochondrial biogenesis; however, the role of this process in lung repair is unknown. We evaluated mitochondrial biogenesis in the mouse lung in two injuries that cause acute inflammation and in two that cause chronic inflammatio...

  16. A metabolomic approach to the pathogenesis of ventilator-induced lung injury

    OpenAIRE

    Izquierdo García, José L.; Naz, Shama; Nin, Nicolás; Rojas, Yeny; Erazo, Marcela; Martínez Caro, Leticia; García, Antonia; De Paula, Marta; Fernández Segoviano, P.; Casals, Cristina; Esteban, Andrés; Ruíz Cabello, Jesús; Barbas, Coral; Lorente Balanza, José Ángel

    2014-01-01

    Global metabolic profiling using quantitative nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) is useful for biomarker discovery. The objective of this study was to discover biomarkers of acute lung injury induced by mechanical ventilation (ventilator-induced lung injury [VILI]), by using MRS and MS. 5.879 JCR (2014) Q1, 1/30 Anesthesiology UEM

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

    Lifescience Database Archive (English)

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

  18. Riboflavin supplementation does not attenuate hyperoxic lung injury in transgenic (spc-mt)hGR mice.

    Science.gov (United States)

    Heyob, Kathryn M; Rogers, Lynette K; Tipple, Trent E; Welty, Stephen E

    2011-04-01

    The aims of this study were to test the hypothesis that mice expressing mitochondrially targeted human glutathione reductase (GR) driven by a surfactant protein C promoter ((spc-mt)hGR) are functionally riboflavin deficient and that this deficiency exacerbates hyperoxic lung injury. The authors further hypothesized that dietary supplementation with riboflavin (FADH) will improve the bioactivity of GR, thus enhancing resistance to hyperoxic lung injury. Transgenic (mt-spc)hGR mice and their nontransgenic littermates were fed control or riboflavin-supplemented diets upon weaning. At 6 weeks of age the mice were exposed to either room air (RA) or >95% O(2) for up to 84 hours. GR activities (with and without exogenous FADH) and GR protein levels were measured in lung tissue homogenates. Glutathione (GSH) and glutathione disulfide (GSSG) concentrations were assayed to identify changes in GR activity in vivo. Lung injury was assessed by right lung to body weight ratios and bronchoalveolar lavage protein concentrations. The data showed that enhanced GR activity in the mitochondria of lung type II cells does not protect adult mice from hyperoxic lung injury. Furthermore, the addition of riboflavin to the diets of (spc-mt)hGR mice neither enhances GR activities nor offers protection from hyperoxic lung injury. The results indicated that modulation of mitochondrial GR activity in lung type II cells is not an effective therapy to minimize hyperoxic lung injury.

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

    Directory of Open Access Journals (Sweden)

    Rector Edward S

    2004-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Yuben Moodley

    2016-07-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  2. Smoked marijuana as a cause of lung injury.

    Science.gov (United States)

    Tashkin, D P

    2005-06-01

    In many societies, marijuana is the second most commonly smoked substance after tobacco. While delta9-tetrahydrocannabinol (THC) is unique to marijuana and nicotine to tobacco, the smoke of marijuana, like that of tobacco, consists of a toxic mixture of gases and particulates, many of which are known to be harmful to the lung. Although far fewer marijuana than tobacco cigarettes are generally smoked on a daily basis, the pulmonary consequences of marijuana smoking may be magnified by the greater deposition of smoke particulates in the lung due to the differing manner in which marijuana is smoked. Whereas THC causes modest short-term bronchodilation, regular marijuana smoking produces a number of long-term pulmonary consequences, including chronic cough and sputum, histopathologic evidence of widespread airway inflammation and injury and immunohistochemical evidence of dysregulated growth of respiratory epithelial cells, that may be precursors to lung cancer. The THC in marijuana could contribute to some of these injurious changes through its ability to augment oxidative stress, cause mitochondrial dysfunction, and inhibit apoptosis. On the other hand, physiologic, clinical or epidemiologic evidence that marijuana smoking may lead to chronic obstructive pulmonary disease or respiratory cancer is limited and inconsistent. Habitual use of marijuana is also associated with abnormalities in the structure and function of alveolar macrophages, including impairment in microbial phagocytosis and killing that is associated with defective production of immunostimulatory cytokines and nitric oxide, thereby potentially predisposing to pulmonary infection. In view of the growing interest in medicinal marijuana, further epidemiologic studies are needed to clarify the true risks of regular marijuana smoking on respiratory health.

  3. Extent and computed tomography appearance of early radiation induced lung injury for non-small cell lung cancer

    DEFF Research Database (Denmark)

    Bernchou, Uffe; Christiansen, Rasmus Lübeck; Asmussen, Jon Thor

    2017-01-01

    BACKGROUND AND PURPOSE: The present study investigates the extent and appearance of radiologic injury in the lung after radiotherapy for non-small cell lung cancer (NSCLC) patients and correlates radiologic response with clinical and dosimetric factors. METHODS AND MATERIALS: Eligible follow-up C...

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

    Science.gov (United States)

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

    2010-07-25

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

  5. Mechanical ventilation injury and repair in extremely and very preterm lungs.

    Directory of Open Access Journals (Sweden)

    Nadine Brew

    Full Text Available BACKGROUND: Extremely preterm infants often receive mechanical ventilation (MV, which can contribute to bronchopulmonary dysplasia (BPD. However, the effects of MV alone on the extremely preterm lung and the lung's capacity for repair are poorly understood. AIM: To characterise lung injury induced by MV alone, and mechanisms of injury and repair, in extremely preterm lungs and to compare them with very preterm lungs. METHODS: Extremely preterm lambs (0.75 of term were transiently exposed by hysterotomy and underwent 2 h of injurious MV. Lungs were collected 24 h and at 15 d after MV. Immunohistochemistry and morphometry were used to characterise injury and repair processes. qRT-PCR was performed on extremely and very preterm (0.85 of term lungs 24 h after MV to assess molecular injury and repair responses. RESULTS: 24 h after MV at 0.75 of term, lung parenchyma and bronchioles were severely injured; tissue space and myofibroblast density were increased, collagen and elastin fibres were deformed and secondary crest density was reduced. Bronchioles contained debris and their epithelium was injured and thickened. 24 h after MV at 0.75 and 0.85 of term, mRNA expression of potential mediators of lung repair were significantly increased. By 15 days after MV, most lung injury had resolved without treatment. CONCLUSIONS: Extremely immature lungs, particularly bronchioles, are severely injured by 2 h of MV. In the absence of continued ventilation these injured lungs are capable of repair. At 24 h after MV, genes associated with injurious MV are unaltered, while potential repair genes are activated in both extremely and very preterm lungs.

  6. Stem cell factor improves lung recovery in rats following neonatal hyperoxia-induced lung injury

    Science.gov (United States)

    Miranda, Luis F.; Rodrigues, Claudia O.; Ramachandran, Shalini; Torres, Eneida; Huang, Jian; Klim, Jammie; Hehre, Dorothy; McNiece, Ian; Hare, Joshua M.; Suguihara, Cleide Y.; Young, Karen C.

    2016-01-01

    BACKGROUND Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis. METHODS Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 µg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay. RESULTS As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs. CONCLUSION Exogenous SCF restores alveolar and vascular structure in neonatal rats with HILI by promoting neoangiogenesis. These findings suggest a new strategy to treat lung diseases characterized by dysangiogenesis. PMID:24153399

  7. Bronchoscopy-derived correlates of lung injury following inhalational injuries: a prospective observational study.

    Directory of Open Access Journals (Sweden)

    Samuel W Jones

    Full Text Available BACKGROUND: Acute lung injury (ALI is a major factor determining morbidity following burns and inhalational injury. In experimental models, factors potentially contributing to ALI risk include inhalation of toxins directly causing cell damage; inflammation; and infection. However, few studies have been done in humans. METHODS: We carried out a prospective observational study of patients admitted to the NC Jaycees Burn Center who were intubated and on mechanical ventilation for burns and suspected inhalational injury. Subjects were enrolled over an 8-month period and followed till discharge or death. Serial bronchial washings from clinically-indicated bronchoscopies were collected and analyzed for markers of cell injury and inflammation. These markers were compared with clinical markers of ALI. RESULTS: Forty-three consecutive patients were studied, with a spectrum of burn and inhalation injury severity. Visible soot at initial bronchoscopy and gram negative bacteria in the lower respiratory tract were associated with ALI in univariate analyses. Subsequent multivariate analysis also controlled for % body surface area burns, infection, and inhalation severity. Elevated IL-10 and reduced IL-12p70 in bronchial washings were statistically significantly associated with ALI. CONCLUSIONS: Independently of several factors including initial inhalational injury severity, infection, and extent of surface burns, high early levels of IL-10 and low levels of IL-12p70 in the central airways are associated with ALI in patients intubated after acute burn/inhalation injury. Lower airway secretions can be collected serially in critically ill burn/inhalation injury patients and may yield important clues to specific pathophysiologic pathways.

  8. Suspended animation inducer hydrogen sulfide is protective in an in vivo model of ventilator-induced lung injury

    NARCIS (Netherlands)

    Aslami, H.; Heinen, A.; Roelofs, J.J.T.H.; Zuurbier, C.J.; Schultz, M.J.; Juffermans, N.P.

    2010-01-01

    Acute lung injury is characterized by an exaggerated inflammatory response and a high metabolic demand. Mechanical ventilation can contribute to lung injury, resulting in ventilator-induced lung injury (VILI). A suspended-animation-like state induced by hydrogen sulfide (H2S) protects against hypoxi

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

    Directory of Open Access Journals (Sweden)

    Shih-Tao Wen

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

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

    Directory of Open Access Journals (Sweden)

    Tomclkova L.

    2014-05-01

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

  11. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment

    OpenAIRE

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Chad S Boomershine; Ortiz, Camila; Sherrill, Taylor P.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.

    2011-01-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice tha...

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

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G

    2011-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Tian-Shun Lai

    2015-01-01

    Full Text Available Background: Subsequent neutrophil (polymorphonuclear neutrophil [PMN]-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI, and mesenchymal stem cell (MSC can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair of VILI. However, whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown. This study aimed to test whether MSC intervention could attenuate the PMN-predominate inflammatory in the mechanical VILI. Methods: Sprague-Dawley rats were ventilated for 2 hours with large tidal volume (20 mL/kg. MSCs were given before or after ventilation. The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation, and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation. Results: Mechanical ventilation (MV caused significant lung injury reflected by increasing in PMN pulmonary sequestration, inflammatory chemokines (tumor necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein 2 in the bronchoalveolar lavage fluid, and injury score of the lung tissue. These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity, production of radical oxygen series. MSC intervention especially pretreatment attenuated subsequent lung injury, systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation. Conclusions: MV causes profound lung injury and PMN-predominate inflammatory responses. The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.

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

    Institute of Scientific and Technical Information of China (English)

    Tian-Shun Lai; Zhi-Hong Wang; Shao-Xi Cai

    2015-01-01

    Background:Subsequent neutrophil (polymorphonuclear neutrophil [PMN])-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI),and mesenchymal stem cell (MSC) can improve mice survival model of endotoxin-induced acute lung injury,reduce lung impairs,and enhance the repair of VILI.However,whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown.This study aimed to test whether MSC intervention could attenuate the PMN-predominate inflammatory in the mechanical VILI.Methods:Sprague-Dawley rats were ventilated for 2 hours with large tidal volume (20 mL/kg).MSCs were given before or after ventilation.The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation,and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation.Results:Mechanical ventilation (MV) caused significant lung injury reflected by increasing in PMN pulmonary sequestration,inflammatory chemokines (tumor necrosis factor-alpha,interleukin-6 and macrophage inflammatory protein 2) in the bronchoalveolar lavage fluid,and injury score of the lung tissue.These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity,production of radical oxygen series.MSC intervention especially pretreatment attenuated subsequent lung injury,systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation.Conclusions:MV causes profound lung injury and PMN-predominate inflammatory responses.The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.

  15. High bias gas flows increase lung injury in the ventilated preterm lamb.

    Directory of Open Access Journals (Sweden)

    Katinka P Bach

    Full Text Available BACKGROUND: Mechanical ventilation of preterm babies increases survival but can also cause ventilator-induced lung injury (VILI, leading to the development of bronchopulmonary dysplasia (BPD. It is not known whether shear stress injury from gases flowing into the preterm lung during ventilation contributes to VILI. METHODS: Preterm lambs of 131 days' gestation (term = 147 d were ventilated for 2 hours with a bias gas flow of 8 L/min (n = 13, 18 L/min (n = 12 or 28 L/min (n = 14. Physiological parameters were measured continuously and lung injury was assessed by measuring mRNA expression of early injury response genes and by histological analysis. Control lung tissue was collected from unventilated age-matched fetuses. Data were analysed by ANOVA with a Tukey post-hoc test when appropriate. RESULTS: High bias gas flows resulted in higher ventilator pressures, shorter inflation times and decreased ventilator efficiency. The rate of rise of inspiratory gas flow was greatest, and pulmonary mRNA levels of the injury markers, EGR1 and CTGF, were highest in lambs ventilated with bias gas flows of 18 L/min. High bias gas flows resulted in increased cellular proliferation and abnormal deposition of elastin, collagen and myofibroblasts in the lung. CONCLUSIONS: High ventilator bias gas flows resulted in increased lung injury, with up-regulation of acute early response genes and increased histological lung injury. Bias gas flows may, therefore, contribute to VILI and BPD.

  16. Protective effect of albumin on lung injury in traumatic/hemorrhagic shock in rats

    Institute of Scientific and Technical Information of China (English)

    DING Chen-yan; CHEN Zuo-bing; ZHENG Shu-sen; GAO Yuan; ZHANG Yun; ZHAO Xue-hong; NI Ling-mei

    2005-01-01

    Objective: To determine the effect of albumin administration on lung injury in traumatic/hemorrhagic shock (T/HS) in rats. Methods: Forty-eight adult Sprague-Dawley rats were divided into three groups randomly (n=16 in each group): Group A, Group B, Group C. In Group A, rats underwent laparotomy without shock. In Group B, rats undergoing T/HS were resuscitated with their blood plus lactated Ringer's (twice the volume of shed blood). In Group C, rats undergoing T/HS were resuscitated with their shed blood plus additional 3 ml of 5% human albumin. The expression of polymorphonuclear neutrophils CD18/CD11b in jugular vein blood was evaluated. The main lung injury indexes (the activity of myeloperoxidase and lung injury score) were measured. Results: Significant differences of the expression of CD18/11b and the severity degree of lung injury were found between the three groups.(P<0.05). The expression of CD18/CD11b and the main lung injury indexes in Group B and Goup C incresed significantly compared with those in Group A(P<0.05).At the same time, the expression of CD18/CD11b and the main lung injury indexes in Group C decreased dramatically, compared with those in Group B (P<0.05). Conclusions: The infusion of albumin during resuscitation period can protect lungs from injury and decrease the expression of CD18/CD11b in T/HS rats.

  17. High Bias Gas Flows Increase Lung Injury in the Ventilated Preterm Lamb

    Science.gov (United States)

    Bach, Katinka P.; Kuschel, Carl A.; Hooper, Stuart B.; Bertram, Jean; McKnight, Sue; Peachey, Shirley E.; Zahra, Valerie A.; Flecknoe, Sharon J.; Oliver, Mark H.; Wallace, Megan J.; Bloomfield, Frank H.

    2012-01-01

    Background Mechanical ventilation of preterm babies increases survival but can also cause ventilator-induced lung injury (VILI), leading to the development of bronchopulmonary dysplasia (BPD). It is not known whether shear stress injury from gases flowing into the preterm lung during ventilation contributes to VILI. Methods Preterm lambs of 131 days’ gestation (term = 147 d) were ventilated for 2 hours with a bias gas flow of 8 L/min (n = 13), 18 L/min (n = 12) or 28 L/min (n = 14). Physiological parameters were measured continuously and lung injury was assessed by measuring mRNA expression of early injury response genes and by histological analysis. Control lung tissue was collected from unventilated age-matched fetuses. Data were analysed by ANOVA with a Tukey post-hoc test when appropriate. Results High bias gas flows resulted in higher ventilator pressures, shorter inflation times and decreased ventilator efficiency. The rate of rise of inspiratory gas flow was greatest, and pulmonary mRNA levels of the injury markers, EGR1 and CTGF, were highest in lambs ventilated with bias gas flows of 18 L/min. High bias gas flows resulted in increased cellular proliferation and abnormal deposition of elastin, collagen and myofibroblasts in the lung. Conclusions High ventilator bias gas flows resulted in increased lung injury, with up-regulation of acute early response genes and increased histological lung injury. Bias gas flows may, therefore, contribute to VILI and BPD. PMID:23056572

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

    Directory of Open Access Journals (Sweden)

    Haji Altaf

    2008-10-01

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

  19. Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.L. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Hu, G.C. [Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL (United States); Zhu, S.S. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Li, J.F. [Department of Anesthesiology, Tengzhou Central People' s Hospital, Liaocheng, Shandong Province (China); Liu, G.J. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China)

    2014-10-14

    The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.

  20. Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats

    Directory of Open Access Journals (Sweden)

    Dyuti Sharma

    2015-09-01

    Full Text Available Bronchopulmonary dysplasia (BPD is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3 during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14 were fed a control diet (n = 2, a PUFA ω-6 diet (n = 6, or a PUFA ω-3 diet (n = 6, starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female were exposed to hyperoxia (O2, n = 70 or to the ambient air (Air, n = 70. Six groups of newborns rats were obtained: PUFA ω-6/O2 (n = 30, PUFA ω-6/air (n = 30, PUFA ω-3/O2 (n = 30, PUFA ω-3/air (n = 30, control/O2 (n = 10, and control/air (n = 10. After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20 and PUFA ω-6 groups (n = 60. Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30 compared to PUFA ω-6/O2 (n = 30 or to the control/O2 (n = 10, but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.

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

    Institute of Scientific and Technical Information of China (English)

    李春盛; 桂培春; 何新华

    2000-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

  3. Molecular signatures of trauma-hemorrhagic shock-induced lung injury: hemorrhage- and injury-associated genes.

    Science.gov (United States)

    Feinman, Rena; Deitch, Edwin A; Aris, Virginie; Chu, Hung B; Abungu, Billy; Caputo, Francis J; Galante, Anthony; Xu, DaZhong; Lu, Qi; Colorado, Iriana; Streck, Deanna; Dermody, James; Soteropoulos, Patricia

    2007-09-01

    The etiology of trauma-hemorrhagic shock (T/HS)-induced acute lung injury has been difficult to elucidate because of, at least in part, the inability of in vivo studies to separate the noninjurious pulmonary effects of trauma-hemorrhage from the tissue-injurious ones. To circumvent this in vivo limitation, we used a model of T/HS in which T/HS lung injury was abrogated by dividing the mesenteric lymph duct. In this way, it was possible to separate the pulmonary injurious response from the noninjurious systemic response to T/HS by comparing the pulmonary molecular responses of rats subjected to T/HS, which did and did not develop lung injury, with those of nonshocked rats. Using high-density oligonucleotide arrays and treatment group comparisons of whole lung tissue collected at 3 h after the end of the shock or sham-shock period, 139 of 8,799 assessed genes were identified by significant analysis of microarrays. Hemorrhage without the secondary effects of lung injury modulated the expression of 21 genes such as interleukin 1beta, metallothionein-2, and myeloctomatosis oncogene (c-myc). In response to injury, 42 genes were identified to be differentially expressed. Upregulated genes included the L1 retroposon and guanine deaminase, whereas downregulated genes included catalase and superoxide dismutase 1. Real-time polymerase chain reaction confirmed the differential expression for selected genes. PathwayAssist analysis identified interleukin 1beta as a central regulator of two subpathways of stress response-related genes (c-myc and superoxide dismutase 1/catalase) as well as several unrelated genes such as lipoprotein lipase. Our model system provided a unique opportunity to distinguish the molecular changes associated with T/HS-induced acute lung injury from the systemic molecular response to T/HS.

  4. CXCR4 Blockade Attenuates Hyperoxia Induced Lung Injury in Neonatal Rats

    Science.gov (United States)

    Drummond, Shelley; Ramachandran, Shalini; Torres, Eneida; Huang, Jian; Hehre, Dorothy; Suguihara, Cleide; Young, Karen C.

    2015-01-01

    Background Lung inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Stromal derived factor-1 (SDF-1) and its receptor chemokine receptor 4 (CXCR4) modulate the inflammatory response. Whether antagonism of CXCR4 will alleviate lung inflammation in neonatal hyperoxia-induced lung injury is unknown. Objective To determine whether CXCR4 antagonism would attenuate lung injury in rodents with experimental BPD by decreasing pulmonary inflammation. Methods Newborn rats exposed to normoxia (RA) or hyperoxia (FiO2=0.9) from postnatal day 2 (P2)-P16 were randomized to receive the CXCR4 antagonist, AMD3100 or placebo (PL) from P5 to P15. Lung alveolarization, angiogenesis, and inflammation were evaluated at P16. Results As compared to RA, hyperoxic-PL pups had a decrease in alveolarization, reduced lung vascular density and increased lung inflammation. In contrast, AMD3100-treated hyperoxic pups had improved alveolarization and increased angiogenesis. This improvement in lung structure was accompanied by a decrease in bronchoalveolar lavage fluid macrophage and neutrophil count and reduced lung myeloperoxidase activity. Conclusion CXCR4 antagonism decreases lung inflammation and improves alveolar as well as vascular structure in neonatal rats with experimental BPD. These findings suggest a novel therapeutic strategy to alleviate lung injury in preterm infants with BPD. PMID:25825119

  5. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bakkal, B.H. [Department of Radiation Oncology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Gultekin, F.A. [Department of General Surgery, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Guven, B. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Turkcu, U.O. [Mugla School of Health Sciences, Mugla Sitki Kocman University, Mugla (Turkey); Bektas, S. [Department of Pathology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Can, M. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey)

    2013-09-27

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  6. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    Directory of Open Access Journals (Sweden)

    B.H. Bakkal

    2013-09-01

    Full Text Available Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg. Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  7. Fibroblast Growth Factor-10 (FGF-10) Mobilizes Lung-resident Mesenchymal Stem Cells and Protects Against Acute Lung Injury.

    Science.gov (United States)

    Tong, Lin; Zhou, Jian; Rong, Linyi; Seeley, Eric J; Pan, Jue; Zhu, Xiaodan; Liu, Jie; Wang, Qin; Tang, Xinjun; Qu, Jieming; Bai, Chunxue; Song, Yuanlin

    2016-02-12

    FGF-10 can prevent or reduce lung specific inflammation due to traumatic or infectious lung injury. However, the exact mechanisms are poorly characterized. Additionally, the effect of FGF-10 on lung-resident mesenchymal stem cells (LR-MSCs) has not been studied. To better characterize the effect of FGF-10 on LR-MSCs, FGF-10 was intratracheally delivered into the lungs of rats. Three days after instillation, bronchoalveolar lavage was performed and plastic-adherent cells were cultured, characterized and then delivered therapeutically to rats after LPS intratracheal instillation. Immunophenotyping analysis of FGF-10 mobilized and cultured cells revealed expression of the MSC markers CD29, CD73, CD90, and CD105, and the absence of the hematopoietic lineage markers CD34 and CD45. Multipotency of these cells was demonstrated by their capacity to differentiate into osteocytes, adipocytes, and chondrocytes. Delivery of LR-MSCs into the lungs after LPS injury reduced the inflammatory response as evidenced by decreased wet-to-dry ratio, reduced neutrophil and leukocyte recruitment and decreased inflammatory cytokines compared to control rats. Lastly, direct delivery of FGF-10 in the lungs of rats led to an increase of LR-MSCs in the treated lungs, suggesting that the protective effect of FGF-10 might be mediated, in part, by the mobilization of LR-MSCs in lungs.

  8. [Analysis of risk factors of drug-induced lung injury in patients receiving gemcitabine treatment].

    Science.gov (United States)

    Nakamichi, Hidenori; Fujita, Tetsuo; Tsuji, Daiki; Atsumi, Ichiko; Totsuka, Kasumi; Suzuki, Rina; Miki, Yoshihiro; Tomita, Kazuhiro; Nakamura, Hidenori; Shiokawa, Mitsuru

    2012-05-01

    Gemcitabine hydrochloride is a very safe medicine that even outpatients can be administered, and the bone marrow depression that is the dose limiting factor remains moderate and does not need special treatment, although it is confirmed in most cases. Meanwhile, caution is required because there is a possibility of drug-induced lung injury and death due to high frequency, compared with the appearance rate described in the packaging insertion. We investigated the clinical background of a patient in whom drug-induced lung injury appeared, and clarified the risk factor by administering gemcitabine hydrochloride. Males, people aged 65 or over, those with a smoking history and those undergoing first-line chemotherapy treatment are at risk of drug-induced lung injury. Attention must be paid to the occurrence of drug-induced lung injury, to examining the clinical course, the chest image, and the blood test, and to do earlier detection, the offending medicine discontinuance, and beginning of the treatment.

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

    Science.gov (United States)

    Gupta, Arjun; Sen, Shiraj; Naina, Harris

    2016-04-06

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

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

    Directory of Open Access Journals (Sweden)

    Carolina Costola-de-Souza

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

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

    DEFF Research Database (Denmark)

    Afshari, Arash; Brok, Jesper; Møller, Ann

    2010-01-01

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

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

    OpenAIRE

    Lee, Jae W

    2009-01-01

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

  13. APRV Mode in Ventilator Induced Lung Injury (VILI

    Directory of Open Access Journals (Sweden)

    Ata Mahmoodpoor

    2014-01-01

    Full Text Available Ventilator-Induced Lung Injury (VILI, being a significant iatrogenic complication in the ICU patients, is associated with high morbidity and mortality. Numerous approaches, protocols and ventilation modes have been introduced and examined to decrease the incidence of VILI in the ICU patients. Airway pressure release ventilation (APRV, firstly introduced by Stock and Downs in 1987, applies higher Continuous Positive Airway Pressure (CPAP levels in prolonged periods (P and T high in order to preserve satisfactory lung volume and consequently alveolar recruitment. This mode benefits a time-cycled release phase to a lower set of pressure for a short period of time (P and T low i.e. release time (1,2. While some advantages have been introduced for APRV such as efficiently recruited alveoli over time, more homogeneous ventilation, less volutrauma, probable stabilization of patent alveoli and reduction in atelectrauma, protective effects of APRV on lung damage only seem to be substantial if spontaneous breathing responds to more than 30% of total minute ventilation (3. APRV in ARDS patients should be administered cautiously; T low<0.6 seconds, for recruiting collapsed alveoli; however overstretching of alveoli especially during P high should not be neglected and appropriate sedation considered. The proposed advantages for APRV give the impression of being outstanding; however, APRV, as a non-physiologic inverse ratio mode of ventilation, might result in inflammation mainly due to impaired patient-ventilator interaction explaining the negative or minimally desirable effects of APRV on inflammation (4. Consequently, continuous infusion of neuromuscular blocking drugs during ARDS has been reported to reduce mortality (5. There are insufficient confirming data on the superiority of APRV above other ventilatory methods in regard to oxygenation, hemodynamics, regional blood flow, patient comfort and length of mechanical ventilation. Based on current findings

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

    Peters, A.L.

    2017-01-01

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

  16. Protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury in a rat model.

    Science.gov (United States)

    Liu, Wenwu; Liu, Kehuan; Ma, Chunqing; Yu, Jiangang; Peng, Zhaoyun; Huang, Guoyang; Cai, Zhiyu; Li, Runping; Xu, Weigang; Sun, Xuejun; Liu, Kan; Zheng, Juan

    2014-01-01

    Hyperbaric oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia leads to inflammation and acute lung injury. This study aimed to investigate the protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury. Rats were intraperitoneally treated with sodium hydrosulphide (NaHS) at 28 μmol/kg immediately before hyperoxia exposure and then exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) with continuous ventilation for six hours, Immediately after hyperoxia exposure, rats were sacrificed via anesthesia. The bronchoalveolar lavage fluid (BALF) was harvested for the detection of protein concentration and IL-1 content, and the lungs were collected for HE staining, TUNEL staining and detection of wet/dry weight ratio. Our results showed hyperbaric hyperoixa exposure could significantly damage the lung (HE staining), increase the protein and IL-13 in the BALF, elevate the wet/dry Weight ratio and raise the TUNEL positive cells. However, pre-treatment with hydrogen sulfide improved the lung morphology, reduced the TUNEL positive cells and attenuated the lung inflammation (reduction in IL-13 of BALF and HE staining). Taken together, our findings indicate that hydrogen sulfide pretreatment may exert protective effects on hyperbaric hyperoxia-induced lung injury.

  17. Radiological and functional assessment of radiation-induced lung injury in the rat

    NARCIS (Netherlands)

    Vujaskovic, Z; Down, JD; van t'Veld, AA; Mooyaart, EL; Meertens, H; Piers, DA; Szabo, BG; Konings, AWT

    1998-01-01

    The purpose of this study is to develop an experimental model to measure localized radiation-induced lung injury using multiple end-points including breathing frequency, high-resolution computed tomography (CT), and radionuclide perfusion. The rats were anaesthetized and the right lung irradiated wi

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

    Science.gov (United States)

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

    2015-10-01

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

  19. Nitric Oxide as a Mediator of Oxidant Lung Injury Due to Paraquat

    Science.gov (United States)

    Berisha, Hasan I.; Pakbaz, Hedayatollah; Absood, Afaf; Said, Sami I.

    1994-08-01

    At low concentrations, nitric oxide is a physiological transmitter, but in excessive concentrations it may cause cell and tissue injury. We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue. All signs of injury, including increased airway and perfusion pressures, pulmonary edema, and protein leakage into the airspaces, were dose-dependently attenuated or totally prevented by either N^G-nitro-L-arginine methyl ester or N^ω-nitro-L-arginine, selective and competitive inhibitors of nitric oxide synthase. Protection was reversed by excess L-arginine but not by its enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat injury was moderated or delayed as it was when paraquat was given to anesthetized guinea pigs. The rapid onset of injury and its failure to occur in the absence of Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was responsible for the stimulated nitric oxide synthesis. The findings indicate that nitric oxide plays a critical role in the production of lung tissue injury due to paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue injury.

  20. Addition of ulinastatin to preservation solution promotes protection against ischemia-reperfusion injury in rabbit lung

    Institute of Scientific and Technical Information of China (English)

    XU Ming; WEN Xiao-hong; CHEN Shu-ping; AN Xiao-xia; XU He-yun

    2011-01-01

    Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose (LPDG), an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion (I/R) injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution alone.Methods Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50 000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis (PaO2, PaCO2), mean pulmonary artery pressure (MPAP) and serum TNF-α level were measured intermittently. The pulmonary water index (D/W), tissue myeloperoxidase (MPO) activity, tissue malondialdehyde (MDA) content and morphologic changes were analyzed.Results The study group showed significantly higher PaO2 and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two groups.Conclusions This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions,inhibiting the release of inflammatory factors and neutrophils immigration.

  1. Penetrating injury of the lungs and multiple injuries of lower extremities caused by aircraft bombs splinters

    Directory of Open Access Journals (Sweden)

    Golubović Zoran

    2010-01-01

    Full Text Available Introduction. Injuries caused by aircraft bombs cause severe damages to the human body. They are characterized by massive destruction of injured tissues and organs, primary contamination by polymorph bacterial flora and modified reactivity of the body. Upon being wounded by aircraft bombs projectiles a victim simultaneously sustains severe damages of many organs and organ systems due to the fact that a large number of projectiles at the same time injure the chest, stomach, head and extremities. Case report. We presented a patient, 41 years of age, injured by aircraft bomb with hemo-pneumothorax and destruction of the bone and soft tissue structures of the foot, as well as the treatment result of such heavy injuries. After receiving thoracocentesis and short reanimation, the patient underwent surgical procedure. The team performed thoracotomy, primary treatment of the wound and atypical resection of the left lung. Thoracic drains were placed. The wounds on the lower leg and feet were treated primarily. Due to massive destruction of bone tissue of the right foot by cluster bomb splinters, and impossibility of reconstruction of the foot, guillotine amputation of the right lower leg was performed. Twelve days after the wounding caused by cluster bomb splinters, soft tissue of the left lower leg was covered by Tirsch free transplantant and the defect in the area of the left foot was covered by dorsalis pedis flap. The transplant and flap were accepted and the donor sites were epithelized. Twenty-six days following the wounding reamputation was performed and amputation stump of the right lower leg was closed. The patient was given a lower leg prosthesis with which he could move. Conclusion. Upon being wounded by aircraft bomb splinters, the injured person sustains severe wounds of multiple organs and organ systems due to simultaneous injuries caused by a large number of projectiles. It is necessary to take care of the vital organs first because they

  2. Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation.

    Science.gov (United States)

    McKallip, Robert J; Ban, Hao; Uchakina, Olga N

    2015-01-01

    Exposure to bacterial endotoxins, such as lipopolysaccharide (LPS), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for LPS-induced inflammation. In the current study, we investigated the potential use of the hyaluronic acid (HA) synthesis inhibitor 4-methylumbelliferone (4-MU) on LPS-induced acute lung inflammation. Culturing LPS-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production, and an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from LPS-induced lung injury. Specifically, 4-MU treatment led to a reduction in LPS-induced hyaluronic acid synthase (HAS) messenger RNA (mRNA) levels, reduction in lung permeability, and reduction in proinflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target HA production may be an effective treatment for the inflammatory response following exposure to LPS.

  3. Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

    Directory of Open Access Journals (Sweden)

    Olga N. Uchakina

    2013-10-01

    Full Text Available Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB, can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS. To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU on staphylococcal enterotoxin B (SEB induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB.

  4. The role of iron in Libby amphibole-induced acute lung injury and inflammation.

    Science.gov (United States)

    Shannahan, Jonathan H; Ghio, Andrew J; Schladweiler, Mette C; McGee, John K; Richards, Judy H; Gavett, Stephen H; Kodavanti, Urmila P

    2011-05-01

    Complexation of host iron (Fe) on the surface of inhaled asbestos fibers has been postulated to cause oxidative stress contributing to in vivo pulmonary injury and inflammation. We examined the role of Fe in Libby amphibole (LA; mean length 4.99 µm ± 4.53 and width 0.28 µm ± 0.19) asbestos-induced inflammogenic effects in vitro and in vivo. LA contained acid-leachable Fe and silicon. In a cell-free media containing FeCl(3), LA bound #17 µg of Fe/mg of fiber and increased reactive oxygen species generation #3.5 fold, which was reduced by deferoxamine (DEF) treatment. In BEAS-2B cells exposure to LA, LA loaded with Fe (FeLA), or LA with DEF did not increase HO-1 or ferritin mRNA expression. LA increased IL-8 expression, which was reduced by Fe loading but increased by DEF. To determine the role of Fe in LA-induced lung injury in vivo, spontaneously hypertensive rats were exposed intratracheally to either saline (300 µL), DEF (1 mg), FeCl(3) (21 µg), LA (0.5 mg), FeLA (0.5 mg), or LA + DEF (0.5 mg). LA caused BALF neutrophils to increase 24 h post-exposure. Loading of Fe on LA but not chelation slightly decreased neutrophilic influx (LA + DEF > LA > FeLA). At 4 h post-exposure, LA-induced lung expression of MIP-2 was reduced in rats exposed to FeLA but increased by LA + DEF (LA + DEF > LA > FeLA). Ferritin mRNA was elevated in rats exposed to FeLA compared to LA. In conclusion, the acute inflammatory response to respirable fibers and particles may be inhibited in the presence of surface-complexed or cellular bioavailable Fe. Cell and tissue Fe-overload conditions may influence the pulmonary injury and inflammation caused by fibers.

  5. [Diagnostics of lung contusion in patients with thoracic closed injury and prophylaxis of complications].

    Science.gov (United States)

    Rachko, Iu V

    2007-01-01

    Among 304 patients hospitalised with thorax closed injury 205 patients had lung contusion. The use of a complex diagnostics allowed to discharge 176 patients without any complications. The development of complections was observed in 128 patients, which occurred after the patients had had their injuries. Application of endoscopic sanation and treatment allowed to discharge patients in early terms.

  6. DEPLETION OF IRON AND ASCORBATE IN RODENTS DIMINISHES LUNG INJURY AFTER SILICA

    Science.gov (United States)

    Exposures of the lung to iron chelates can be associated with an injury. The catalysis of oxygen-based free radicals is postulated to participate in this injury. Such oxidant generation by mineral oxide particles can be dependent on availability of both iron and a reductant. We t...

  7. Experimental study of acute lung injury induced by different tidal volume ventilation in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin-ri; DU Yong-cheng; JIANG Hong-ying; XU Jian-ying; XU Yong-jian

    2005-01-01

    @@ Mechanical ventilation (MV) is a dual blade sward which if misused could lead to lung injury, called ventilator induced lung injury (VILI). Pathogenesis of VILI is very complex with various manifestations, which is the focus in MV field in recent years.1 In our research, the rats were ventilated with different tidal volume, then the pathological changes of the lungs were observed under macroscopy, light and electronic microscope, and various laboratory tests in blood and bronchoalveolar lavage fluid (BALF) were also carried out in order to probe further the pathologic characteristics and the pathogenesis of VILI.

  8. Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injury.

    Science.gov (United States)

    Liebler, Janice M; Lutzko, Carolyn; Banfalvi, Agnes; Senadheera, Dinithi; Aghamohammadi, Neema; Crandall, Edward D; Borok, Zea

    2008-08-01

    We studied the capacity of adult human bone marrow-derived cells (BMDC) to incorporate into distal lung of immunodeficient mice following lung injury. Immunodeficient NOD/SCID and NOD/SCID/beta(2) microglobulin (beta(2)M)(null) mice were administered bleomycin (bleo) or saline intranasally. One, 2, 3 and 4 days after bleo or saline, human BMDC labeled with CellTracker Green CMFDA (5-chloromethylfluorescein diacetate) were infused intravenously. Retention of CMFDA(+) cells was maximal when delivered 4 days after bleo treatment. Seven days after bleo, cells from NOD/SCID mice were CMFDA(+), which increased 10- to 100-fold in NOD/SCID/beta(2)M(null) mice. Preincubation of BMDC with Diprotin A, a reversible inhibitor of CD26 peptidase activity that enhances the stromal-derived factor-1 (SDF-1/CXCL12)/CXCR4 axis, resulted in a 30% increase in the percentage of CMFDA(+) cells retained in the lung. These data indicate that human BMDC can be identified in lungs of mice following injury, albeit at low levels, and this may be modestly enhanced by manipulation of the SDF-1/CXCR4 axis. Given the overall low number of human cells detected, methods to increase homing and retention of adult BMDC, and consideration of other stem cell populations, will likely be required to facilitate engraftment in the treatment of lung injury.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2012-08-01

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

  11. Lactobacillus rhamnosus GG and Bifidobacterium longum attenuate lung injury and inflammatory response in experimental sepsis.

    Directory of Open Access Journals (Sweden)

    Ludmila Khailova

    Full Text Available INTRODUCTION: Probiotic use to prevent nosocomial gastrointestinal and potentially respiratory tract infections in critical care has shown great promise in recent clinical trials of adult and pediatric patients. Despite well-documented benefits of probiotic use in intestinal disorders, the potential for probiotic treatment to reduce lung injury following infection and shock has not been well explored. OBJECTIVE: Evaluate if Lactobacillus rhamnosus GG (LGG or Bifidobacterium longum (BL treatment in a weanling mouse model of cecal ligation and puncture (CLP peritonitis will protect against lung injury. METHODS: 3 week-old FVB/N mice were orally gavaged with 200 µl of either LGG, BL or sterile water (vehicle immediately prior to CLP. Mice were euthanized at 24 h. Lung injury was evaluated via histology and lung neutrophil infiltration was evaluated by myeloperoxidase (MPO staining. mRNA levels of IL-6, TNF-α, MyD88, TLR-4, TLR-2, NFΚB (p50/p105 and Cox-2 in the lung analyzed via real-time PCR. TNF-α and IL-6 in lung was analyzed via ELISA. RESULTS: LGG and BL treatment significantly improved lung injury following experimental infection and sepsis and lung neutrophil infiltration was significantly lower than in untreated septic mice. Lung mRNA and protein levels of IL-6 and TNF-α and gene expression of Cox-2 were also significantly reduced in mice receiving LGG or BL treatment. Gene expression of TLR-2, MyD88 and NFΚB (p50/p105 was significantly increased in septic mice compared to shams and decreased in the lung of mice receiving LGG or BL while TLR-4 levels remained unchanged. CONCLUSIONS: Treatment with LGG and BL can reduce lung injury following experimental infection and sepsis and is associated with reduced lung inflammatory cell infiltrate and decreased markers of lung inflammatory response. Probiotic therapy may be a promising intervention to improve clinical lung injury following systemic infection and sepsis.

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

    李洋

    2013-01-01

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

  14. Role of NLRP3 inflammasomes in lung injury induced by gut hypoxic stress and its mechanism

    Directory of Open Access Journals (Sweden)

    Shi-qiang XIONG

    2015-01-01

    Full Text Available Hypoxic stress of the gut may induce impairment of gut barrier function, ensuing translocation of gutderived factors which can damage the function of remote organs, especially the development of acute lung injury (ALI. High altitude pulmonary edema (HAPE is a non-cardiogenic pulmonary injury caused by hypoxia, while inflammation involved in the pathogenesis of HAPE has been gradually recognized. It has been also recognized that the cleavage and maturation of proinflammatory cytokines mediated by NLRP3 inflammasome play a crucial role in the pathogenesis of lung injury. Further investigation on the role of NLRP3 inflammasome in lung injury induced by gut hypoxic stress is of an important clinical significance for further improvement in the treatment of hypoxic inflammatory diseases. DOI: 10.11855/j.issn.0577-7402.2014.11.14

  15. Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep

    Directory of Open Access Journals (Sweden)

    Kallapur Suhas G

    2009-12-01

    Full Text Available Abstract Background Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia. Objective To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury. Methods 129 d gestational age lambs (n = 5-8/gp; term = 150 d were operatively delivered and ventilated after exposure to either 1 no medication, 2 antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3 0.5 mg/kg Dexamethasone IV at delivery or 4 Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (VT to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with VT 8 mL/kg and PEEP 5 cmH20 for 2 h 45 min. Results High VT ventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids. Conclusions Antenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.

  16. Reproduction and evaluation of a rat model of inhalation lung injury caused by black gunpowder smog

    Directory of Open Access Journals (Sweden)

    Yi-fan LIU

    2013-09-01

    Full Text Available Objective To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6. The arterial blood gas, wet to dry weight ratio (W/D of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (BALF were determined. Macroscopic and microscopic changes in lung tissue were observed. Results The composition of black gunpowder smog was composed mainly of CO2 and CO, and their concentrations remained stable within 12 minutes. Smog inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 1h, and the W/D of lung reached peak value 2h after inhalation (P<0.05. The amount of leukocytes and content of protein in BALF increased significantly within 24h after inhalation (P<0.05. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in lung tissue as manifestations of acute lung injury, and the injury did not recover at 96h after inhalation. Conclusion The rat model of inhalation lung injury can be reproduced using black gunpowder smog, and it has the advantages of its readiness for reproduction, reliability and stability, and it could be used for the experiment of inhalation injury in a battlefield environment.

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

    Science.gov (United States)

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

    2000-12-01

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

  18. Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study.

    Science.gov (United States)

    Moodley, Yuben; Vaghjiani, Vijesh; Chan, James; Baltic, Svetlana; Ryan, Marisa; Tchongue, Jorge; Samuel, Chrishan S; Murthi, Padma; Parolini, Ornella; Manuelpillai, Ursula

    2013-01-01

    Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.

  19. Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study.

    Directory of Open Access Journals (Sweden)

    Yuben Moodley

    Full Text Available Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC, bone marrow MSC (BM-MSC and human amniotic epithelial cells (hAEC in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC, IL-6 (AM-MSC, BM-MSC, hAEC and TNF-α (AM-MSC. The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC. IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.

  20. Membrane translocation of IL-33 receptor in ventilator induced lung injury.

    Directory of Open Access Journals (Sweden)

    Shih-Hsing Yang

    Full Text Available Ventilator-induced lung injury is associated with inflammatory mechanism and causes high mortality. The objective of this study was to discover the role of IL-33 and its ST2 receptor in acute lung injury induced by mechanical ventilator (ventilator-induced lung injury; VILI. Male Wistar rats were intubated after tracheostomy and received ventilation at 10 cm H2O of inspiratory pressure (PC10 by a G5 ventilator for 4 hours. The hemodynamic and respiratory parameters were collected and analyzed. The morphological changes of lung injury were also assessed by histological H&E stain. The dynamic changes of lung injury markers such as TNF-α and IL-1β were measured in serum, bronchoalveolar lavage fluid (BALF, and lung tissue homogenization by ELISA assay. During VILI, the IL-33 profile change was detected in BALF, peripheral serum, and lung tissue by ELISA analysis. The Il-33 and ST2 expression were analyzed by immunohistochemistry staining and western blot analysis. The consequence of VILI by H&E stain showed inducing lung congestion and increasing the expression of pro-inflammatory cytokines such as TNF-α and IL-1β in the lung tissue homogenization, serum, and BALF, respectively. In addition, rats with VILI also exhibited high expression of IL-33 in lung tissues. Interestingly, the data showed that ST2L (membrane form was highly accumulated in the membrane fraction of lung tissue in the PC10 group, but the ST2L in cytosol was dramatically decreased in the PC10 group. Conversely, the sST2 (soluble form was slightly decreased both in the membrane and cytosol fractions in the PC10 group compared to the control group. In conclusion, these results demonstrated that ST2L translocation from the cytosol to the cell membranes of lung tissue and the down-expression of sST2 in both fractions can function as new biomarkers of VILI. Moreover, IL-33/ST2 signaling activated by mechanically responsive lung injury may potentially serve as a new therapy target.

  1. Aerosolized alpha-tocopherol ameliorates acute lung injury following combined burn and smoke inhalation injury in sheep.

    Science.gov (United States)

    Morita, Naoki; Traber, Maret G; Enkhbaatar, Perenlei; Westphal, Martin; Murakami, Kazunori; Leonard, Scott W; Cox, Robert A; Hawkins, Hal K; Herndon, David; Traber, Lillian D; Traber, Daniel L

    2006-03-01

    Victims of fire accidents who sustain both thermal injury to the skin and smoke inhalation have gross evidence of oxidant injury. Therefore, we hypothesized that delivery of vitamin E, an oxygen superoxide scavenger, directly into the airway would attenuate acute lung injury postburn and smoke inhalation. Sheep (N = 17 female, 35 +/- 5 kg) were divided into 3 groups: (1) injured, then nebulized with vitamin E (B&S, Vitamin E, n = 6); (2) injured, nebulized with saline (B&S, Saline, n = 6); and (3) not injured, not treated (Sham, n = 5). While under deep anesthesia with isoflurane, the sheep were subjected to a flame burn (40% total body surface area, 3rd degree) and inhalation injury (48 breaths of cotton smoke, Ringer lactate solution (4 mL/kg/%burn/24 h) and placed on a ventilator [positive end-expiratory pressure (PEEP) = 5 cm H2O, tidal volume = 15 mL/kg] for 48 h. B&S injury halved the lung alpha-tocopherol concentrations (0.9 +/- 0.1 nmol/g) compared with sham-injured animals (1.5 +/- 0.3), whereas vitamin E treatment elevated the lung alpha-tocopherol concentrations (7.40 +/- 2.61) in the injured animals. B&S injury decreased pulmonary gas exchange (PaO2/FiO2 ratios) from 517 +/- 15 at baseline to 329 +/- 49 at 24 h and to 149 +/- 32 at 48 h compared with sham ratios of 477 +/- 14, 536 +/- 48, and 609 +/- 49, respectively. Vitamin E treatment resulted in a significant improvement of pulmonary gas exchange; ratios were 415 +/- 34 and 283 +/- 42 at 24 and 48 h, respectively. Vitamin E nebulization therapy improved the clinical responses to burn and smoke inhalation-induced acute lung injury.

  2. Apneic oxygenation combined with extracorporeal arteriovenous carbon dioxide removal provides sufficient gas exchange in experimental lung injury

    DEFF Research Database (Denmark)

    Nielsen, Niels Dalsgaard; Kjærgaard, Benedict; Nielsen, Jakob Koefoed

    injury was induced by repeated lung lavage. Thereafter the tracheal tube was, after a lung recruitment maneuver, connected to 20 cmH2O continuous positive airway pressure (FiO2 = 1.0) for oxygenation of the blood. A pumpless membrane lung (Interventional Lung Assist, NovaLung, Germany) was connected......Background and aim of study We hypothesized that continuous high airway pressure without ventilatory movements (apneic oxygenation), using an open lung approach, combined with extracorporeal, pumpless, arterio-venous, carbon dioxide (CO2) removal would provide adequate gas exchange in acute lung...... injury. The aim of this study was to test this hypothesis in a lung injury model using pigs of human adult size, to mimic the O2 consumption and the CO2 production of adult patients.   Materials and methods In eight anesthetized, tracheally intubated and mechanically ventilated pigs (85-95 kg), lung...

  3. Spatiotemporal Aeration and Lung Injury Patterns Are Influenced by the First Inflation Strategy at Birth.

    Science.gov (United States)

    Tingay, David G; Rajapaksa, Anushi; Zonneveld, C Elroy; Black, Don; Perkins, Elizabeth J; Adler, Andy; Grychtol, Bartłomiej; Lavizzari, Anna; Frerichs, Inéz; Zahra, Valerie A; Davis, Peter G

    2016-02-01

    Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.

  4. Glutathione Reductase Targeted to Type II Cells Does Not Protect Mice from Hyperoxic Lung Injury

    Science.gov (United States)

    Heyob, Kathryn M.; Rogers, Lynette K.; Welty, Stephen E.

    2008-01-01

    Exposure of the lung epithelium to reactive oxygen species without adequate antioxidant defenses leads to airway inflammation, and may contribute to lung injury. Glutathione peroxidase catalyzes the reduction of peroxides by oxidation of glutathione (GSH) to glutathione disulfide (GSSG), which can in turn be reduced by glutathione reductase (GR). Increased levels of GSSG have been shown to correlate negatively with outcome after oxidant exposure, and increased GR activity has been protective against hyperoxia in lung epithelial cells in vitro. We tested the hypothesis that increased GR expression targeted to type II alveolar epithelial cells would improve outcome in hyperoxia-induced lung injury. Human GR with a mitochondrial targeting sequence was targeted to mouse type II cells using the SPC promoter. Two transgenic lines were identified, with Line 2 having higher lung GR activities than Line 1. Both transgenic lines had lower lung GSSG levels and higher GSH/GSSG ratios than wild-type. Six-week-old wild-type and transgenic mice were exposed to greater than 95% O2 or room air (RA) for 84 hours. After exposure, Line 2 mice had higher right lung/body weight ratios and lavage protein concentrations than wild-type mice, and both lines 1 and 2 had lower GSSG levels than wild-type mice. These findings suggest that GSSG accumulation in the lung may not play a significant role in the development of hyperoxic lung injury, or that compensatory responses to unregulated GR expression render animals more susceptible to hyperoxic lung injury. PMID:18566333

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice

    Science.gov (United States)

    Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula

    2015-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. PMID:26272953

  7. The Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits.

    Directory of Open Access Journals (Sweden)

    Helmut D Hummler

    Full Text Available Permissive hypercapnia has been shown to reduce lung injury in subjects with surfactant deficiency. Experimental studies suggest that hypercapnic acidosis by itself rather than decreased tidal volume may be a key protective factor.To study the differential effects of a lung protective ventilatory strategy or hypercapnic acidosis on gas exchange, hemodynamics and lung injury in an animal model of surfactant deficiency.30 anesthetized, surfactant-depleted rabbits were mechanically ventilated (FiO2 = 0.8, PEEP = 7cmH2O and randomized into three groups: Normoventilation-Normocapnia (NN-group: tidal volume (Vt = 7.5 ml/kg, target PaCO2 = 40 mmHg; Normoventilation-Hypercapnia (NH-group: Vt = 7.5 ml/kg, target PaCO2 = 80 mmHg by increasing FiCO2; and a Hypoventilation-Hypercapnia (HH-group: Vt = 4.5 ml/kg, target PaCO2 = 80 mmHg. Plasma lactate and interleukin (IL-8 were measured every 2 h. Animals were sacrificed after 6 h to perform bronchoalveolar lavage (BAL, to measure lung wet-to-dry weight, lung tissue IL-8, and to obtain lung histology.PaO2 was significantly higher in the HH-group compared to the NN-group (p<0.05, with values of the NH-group between the HH- and NN-groups. Other markers of lung injury (wet-dry-weight, BAL-Protein, histology-score, plasma-IL-8 and lung tissue IL-8 resulted in significantly lower values for the HH-group compared to the NN-group and trends for the NH-group towards lower values compared to the NN-group. Lactate was significantly lower in both hypercapnia groups compared to the NN-group.Whereas hypercapnic acidosis may have some beneficial effects, a significant effect on lung injury and systemic inflammatory response is dependent upon a lower tidal volume rather than resultant arterial CO2 tensions and pH alone.

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

    Science.gov (United States)

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

    2005-08-01

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

  9. Amino acids and metal ions protect endothelial cells from lethal injury

    Energy Technology Data Exchange (ETDEWEB)

    Varani, J.; Ginsburg, I.; Johnson, K.J.; Gibbs, D.F.; Weinberg, J.M.; Ward, P.A. (Univ. of Michigan, Ann Arbor (United States))

    1991-03-11

    Killing of rat pulmonary artery endothelial cells by activated neutrophils is dependent on generation of hydrogen peroxide and its conversion to a highly toxic radical (presumably the hydroxyl radical) in a ferrous iron-dependent reaction. Glycine (as well as several other amino acids) is capable of inhibiting endothelial cell killing in vitro by either activated neutrophils or reagent hydrogen peroxide. Inhibition of killing is enhanced in the presence of micromolar concentrations of manganous ion (Mn2+). The combined effects of glycine and Mn2+ require concomitant presence of bicarbonate ion and is inhibited by high phosphate levels. Glycine can also protect endothelial cells from lethal injury inducted by ionomycin. There appears to be no enhancement with Mn2+, however against this form of lethal injury. The protective effects of glycine, Mn2+ and bicarbonate ion against injury by hydrogen peroxide is associated with a direct disproportionation of the hydrogen peroxide to water with little generation of molecular oxygen. Either glycine or Mn2+ alone does not have this effect. In addition to protecting endothelial cells from hydrogen peroxide-mediated injury, glycine or MN2+ is almost completely protective. Additionally, treatment of rats with concentrations of EDTA that do not by themselves induce injury greatly accentuates lung injury induced by glucose oxidase. These findings suggest that circulating amino acids in combination with Mn2+ and bicarbonate ions may contribute to the normal anti-oxidant barrier. These findings may also form the basis for a possible new therapeutic approach to oxygen radical-mediated injury.

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

    Institute of Scientific and Technical Information of China (English)

    Guang-Ping Fan

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maria Entezari

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Junko Kosaka

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

  13. Effects of pentoxifylline on TNF-alpha and lung histopathology in HCL-induced lung injury

    Directory of Open Access Journals (Sweden)

    Itamar Souza de Oliveira-Júnior

    2008-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of pentoxifylline on hydrochloric acid-induced lung lesions in rats subjected to mechanical ventilation. METHODS: Twenty male, adult Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group as follows: control-MV (mechanical ventilation, MV group; bilateral instillation of HCl (HCl group; bilateral instillation of HCl followed by pentoxifylline (50 mg/kg bw infusion (HCl+PTX group and pentoxifylline infusion followed by bilateral instillation of HCl (PTX+HCl group. At 20, 30, 90 and 180 min after treatments, the blood partial pressures of CO2 and O2 were measured. The animals were euthanized, and bronchoalveolar lavages were taken to determine the contents of total proteins, corticosterone and TNF-alpha. Samples of lung tissue were used for histomorphometric studies and determining the wet-to-dry (W/D lung weight ratio. RESULTS: In the MV group, rats had alveolar septal congestion, and, in the HCl group, a remarkable recruitment of neutrophils and macrophages into the alveoli was noticed; these events were reduced in the animals with PTX+HCl. The partial pressure of oxygen increased in PTX+HCl animals (121±5 mmHg as compared with the HCl (62±6 mmHg and HCl+PTX (67±3 mmHg groups within 30 minutes. TNF-alpha levels in bronchoalveolar lavage were significantly higher in the HCl group (458±50 pg/mL, reduced in the HCl+PTX group (329±45 pg/mL and lowest in the PTX+HCl group (229±41 pg/mL. The levels of corticosterone in bronchoalveolar lavage were significantly lower in the HCl (8±1.3 ng/mL and HCl+PTX group (16±2 ng/mL and were highest in the PTX+HCl (27±1.9 ng/mL. CONCLUSION: Pretreatment with PTX improves oxygenation, reduces TNF-alpha concentration and increases the concentration of corticosterone in bronchoalveolar lavage upon lung lesion induced by HCl.

  14. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Inoue Takehiro

    2010-04-01

    Full Text Available Abstract Background Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6 is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA could ameliorate radiation-induced lung injury in mice. Methods BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1 or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA. Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. Results The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Conclusions Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

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

    Directory of Open Access Journals (Sweden)

    Xun Liang

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

  16. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751 (Egypt); Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Omar, Hany A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Maghrabi, Ibrahim A. [Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); AlSaeed, Mohammed S. [Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); EL-Tarras, Adel E. [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia)

    2014-01-01

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

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

    Science.gov (United States)

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

    2013-07-01

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

  18. Infliximab attenuates activated charcoal and polyethylene glycol aspiration-induced lung injury in rats.

    Science.gov (United States)

    Güzel, Aygül; Günaydin, Mithat; Güzel, Ahmet; Alaçam, Hasan; Murat, Naci; Gacar, Ayhan; Güvenç, Tolga

    2012-04-01

    Aspiration is a serious complication of gastrointestinal (GI) decontamination procedure. Studies have shown that tumor necrosis factor-α (TNF-α) blockers have beneficial effects on lung injury. Therefore, the authors investigated the attenuation by infliximab (INF) on activated charcoal (AC)- and polyethylene glycol (PEG)-induced lung injury in rat model. Forty-two male Sprague-Dawley rats were allotted into 1 of 6 groups: saline (NS), activated charcoal (AC), polyethylene glycol (PEG), NS+INF treated, AC+INF treated, and PEG+INF treated. All materials were aspirated into the lungs at a volume of 1 mL/kg. Before aspiration, the rats were injected subcutaneously with INF. Seven days later, both lungs and serum specimens in all groups were evaluated histopathologically, immunohistochemically, and biochemically. Following aspiration of AC and PEG, evident histopathological changes were assigned in the lung tissue that were associated with increased expression of inducible nitric oxide synthase (iNOS), increased serum levels of oxidative stress markers (malondialdehyde [MDA], surfactant protein-D [SP-D], TNF-α), and decreased antioxidant enzyme (glutathione peroxidase [GSH-Px]) activities. INF treatment significantly decreased the elevated serum MDA and TNF-α levels and increased serum GSH-Px levels. Furthermore, the current results show that there is a significant reduction in the activity of iNOS in lung tissue and increased serum SP-D levels of AC and PEG aspiration-induced lung injury with INF treatment. These findings suggest that INF attenuates lung inflammation and prevents GI decontamination agent-induced lung injury in rats.

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

    Directory of Open Access Journals (Sweden)

    Guo Li

    2015-01-01

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

  20. Role of eicosanoids in a model of smoke-induced lung injury. Final report, 1 June 1987-4 June 1988

    Energy Technology Data Exchange (ETDEWEB)

    Witten, M.L.

    1988-06-29

    Smoke inhalation has been identified as a major cause of lung injury and death in fires with mortality rate of approximately 75%. Soldiers regularly occupy enclosed spaces and travel near flammable fuels. The combination of burning material and an enclosed space are major factors that lead to smoke inhalation. A combination of diesel fuel and polycarbonate plastic was used to generate smoke-induced lung injury. Rabbits were exposed to 60 tidal-volume breaths of smoke in approximately 10 minutes. Acute smoke-exposure caused changes in broncho-alveolar lavage (BAL) and plasma eicosanoid concentration, especially at 0.5 hours post-smoke exposure. In addition, there were decreases in technetium-labeled diethylene-triamine pentaacetic acid (99mTcDTPA) T1/2, increases in BAL total white cell count and alveolar macrophage acid phosphatase activity, and pathological evidence of pulmonary edema and type 2 pneumocyte injury. It is concluded that lung eicosanoids are involved in the inflammatory process caused by severe smoke inhalation. However, the specific roles these lung eicosanoids play in the smoke-induced injury process are not known at this time.

  1. Pancreatic enzymes in the gut contributing to lung injury after trauma/hemorrhagic shock

    Institute of Scientific and Technical Information of China (English)

    石汉平; 刘正军; 闻英

    2004-01-01

    Objective: To examine whether pancreatic proteolytic enzymes involve in lung injury induced by trauma/hemorrhagic shock (T/HS). Results: Lung permeability, pulmonary myeloperoxidase levels and the ratio of bronchoalveolar lavage fluid protein to plasma protein increased after T/HS, and significantly decreased in intraluminal-ANGD treated but not in intravenous-ANGD treated rats. Histological analysis demonstrated fewer injured villi in the intraluminal-ANGD treated rats compared with those in the control rats. Linear regression analysis revealed that the percentage of injured ileal mucosal villi directly related to pulmonary polymorphic neutrophil sequestration and lung permeability to Evans blue dye. Conclusions: Pancreatic proteolytic enzymes in the ischemic gut may be important toxic factors contributing to lung injury after T/HS.

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

    Institute of Scientific and Technical Information of China (English)

    李春盛; 周景; 桂培春; 何新华

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bakowitz Magdalena

    2012-08-01

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

  4. Multislice spiral computed tomography to determine the effects of a recruitment maneuver in experimental lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Henzler, Dietrich; Rossaint, Rolf [University Hospital, RWTH Aachen, Anesthesiology Department, Aachen (Germany); Mahnken, Andreas H.; Wildberger, Joachim E.; Guenther, Rolf W. [University Hospital of the RWTH Aachen, Clinic of Diagnostic Radiology, Aachen (Germany); Kuhlen, Ralf [University Hospital of the RWTH Aachen, Operative Intensive Care Department, Aachen (Germany)

    2006-06-15

    Although recruitment of atelectatic lung is a common aim in acute respiratory distress syndrome (ARDS), the effects of a recruitment maneuver have not been assessed quantitatively. By multislice spiral CT (MSCT), we analyzed the changes in lung volumes calculated from the changes in the CT values of hyperinflated (V{sub HYP}), normally (V{sub NORM}), poorly (V{sub POOR}) and nonaerated (V{sub NON}) lung in eight mechanically ventilated pigs with saline lavage-induced acute lung injury before and after a recruitment maneuver. This was compared to single slice analysis near the diaphragm. The increase in aerated lung was mainly for V{sub POOR} and the less in V{sub NORM}. Total lung volume and intrathoracic gas increased. No differences were found for tidal volumes measured by spirometry or determined by CT. The inspiratory-expiratory volume differences were not different after the recruitment maneuver in V{sub NON} (from 62{+-}18 ml to 43{+-}26 ml, P=0.114), and in V{sub NORM} (from 216{+-}51 ml to 251{+-}37 ml, P=0.102). Single slice analysis significantly underestimated the increase in normally and poorly aerated lung. Quantitative analysis of lung volumes by whole lung MSCT revealed the increase of poorly aerated lung as the main mechanism of a standard recruitment maneuver. MSCT can provide additional information as compared to single slice CT. (orig.)

  5. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment.

    Science.gov (United States)

    Degryse, Amber L; Tanjore, Harikrishna; Xu, Xiaochuan C; Polosukhin, Vasiliy V; Jones, Brittany R; Boomershine, Chad S; Ortiz, Camila; Sherrill, Taylor P; McMahon, Frank B; Gleaves, Linda A; Blackwell, Timothy S; Lawson, William E

    2011-06-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4(+)/β-gal(+)) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine.

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

    Directory of Open Access Journals (Sweden)

    Hadi Najah R

    2011-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    刘瑶

    2014-01-01

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

  8. Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

    Science.gov (United States)

    Erer, Dilek; Özer, Abdullah; Demirtaş, Hüseyin; Gönül, İpek Işık; Kara, Halil; Arpacı, Hande; Çomu, Faruk Metin; Oktar, Gürsel Levent; Arslan, Mustafa; Küçük, Ayşegül

    2016-01-01

    Objectives To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model. Materials and methods Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined. Results Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (Palprostadil- and iloprost-treated groups (P=0.017 and P=0.001; PAlprostadil and iloprost significantly reduce lung tissue I/R injury. Alprostadil has more prominent protective effects against renal I/R injury, while iloprost is superior in terms of protecting the skeletal muscle tissue against I/R injury. PMID:27601882

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

    Directory of Open Access Journals (Sweden)

    Shunying Jin

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

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Protective effect of heme oxygenase-1 on lung injury induced by erythrocyte instillation in rats

    Institute of Scientific and Technical Information of China (English)

    PANG Qing-feng; ZHOU Qiao-mei; ZENG Si; DOU Li-dong; JI Yong; ZENG Yin-ming

    2008-01-01

    Background Intratracheal instillation of blood induces self-repaired acute lung injury.However,the mechanism of repair has been unclear.Heme-oxygenase (HO)-1,which catalyzes heine breakdown,acts as an inducible defense against oxidative stress and plays an important role in inflammation.The objective of this study was to test the role of HO-1 in lung injury caused by intratracheal instillation of red cells.Methods Forty healthy,male Sprague-Dawley rats were randomly divided into five groups:normal group,saline group,erythrocyte group,erythrocyte+zinc-protoporphyrin (ZnPP,HO-1 inhibitor) group and saline+ZnPP group.At 2 days after intratracheal instillation of red cells,lung tissues and lavage samples were isolated for biochemical determinations and histological measurements.Results Histological analysis revealed that administration of ZnPP worsened the acute lung injury induced by instilled erythrocytes.HO-1 was over-expressed in the erythrocyte group and in the erythrocyte+ZnPP group.Compared with the erythrocyte+ZnPP group,the levels of total protein,lactate dehydrogenase and tumor necrosis factor-α in the lavage were lower (P<0.01),while the level of interleukin-10 was higher in the erythrocyte group (P<0.01).Conclusion HO-1 protects against erythrocyte-induced inflammatory injury in lung.

  12. Cellular changes in bronchoalveolar lavage fluid in hyperoxia-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    Xinbiao HE; Wei ZHAO

    2008-01-01

    It is well known that high concentration oxy-gen exposure is a model of acute lung injury (ALI). However, controversy exists over the mechanism. This study was designed to clarify the cellular characteristics in bronchoalveolar lavage fluid (BALF) and body weight loss of rats exposed to oxygen(>90%). Young male Wistar rats, aged 6 weeks, were divided into three groups: (1) room air group (exposed to room air, n=22); (2) hyperoxia < 48 h group (exposed to over 90% oxygen for less than 48 h, n=18); (3) hyperoxia 66-72 h group (exposed to over 90% oxygen for 66-72 h group, n=7). Compared to the room air group, the total cell counts in the hyperoxia 66-72 h group decreased, whereas the neu-trophils increased significantly. The body weights of the rats exposed to room air continued to increase. However, the body weights of oxygen-exposed rats increased slightly on the first day and weight loss was seen from the second day. All rats were noted to have bilateral pleural effusion in the hyperoxia 66-72 h group. The data suggests that (1) an increase in neutrophil count is an evident feature of hyperoxia-induced lung injury; (2) high concentration oxygen exposure can give rise to anorexia and malnutri-tion, which may play a role in hyperoxia-induced lung injury. Blocking neutrophil influx into lung tissue in the early phase and improving malnutrition are two effective methods to reduce hyperoxic lung injury.

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

    Science.gov (United States)

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

    1994-03-01

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

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

    Institute of Scientific and Technical Information of China (English)

    周琼; 白明; 邹世清

    2004-01-01

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

  15. Erdosteine ameliorates lung injury induced by transient aortic occlusion in rats.

    Science.gov (United States)

    Kurtoglu, Tunay; Sacar, Mustafa; Inan, Bilal Kaan; Duver, M Harun; Guler, Adem; Ucak, Alper; Us, Melih Hulusi; Yilmaz, Ahmet Turan

    2007-01-01

    The aim of this experimental study was to evaluate the protective effect of erdosteine on lung injury induced by ischaemia-reperfusion (IR) of the lower extremities of rats. Wistar albino rats (n = 21) were divided into three groups. In the IR group (n = 7), the aorta was cross-clamped for two hours, followed by one hour of reperfusion. In the erdosteine group (n = 7), animals were pretreated with erdosteine 100 mg/kg daily via gastric lavage, starting three days before aortic occlusion. In the control group (n 5 7), the lungs were removed and blood samples were taken immediately after sternotomy. No treatment was given in the control and IR groups. After both lungs were removed, biochemical parameters were measured and broncho-alveolar lavage (BAL ) assessment was made. MDA levels and MPO activities in the lung tissue were significantly reduced in the erdosteine group compared to the IR group. BAL assessment revealed decreased neutrophil counts in the erdosteine-treated group. Pretreatment of animals with erdosteine significantly attenuated transient aortic occlusion-induced remote lung injury, characterised by leukocyte accumulation and lipid peroxidation. The results suggest that erdosteine may be beneficial in amelioration of lung injury caused by IR.

  16. Activated protein C protection from lung inflammation in endotoxin-induced injury.

    Science.gov (United States)

    Pirrone, Federica; Mazzola, Silvia M; Pastore, Camilla; Paltrinieri, Saverio; Sironi, Giuseppe; Riccaboni, Pietro; Viola, Manuela; Passi, Alberto; Clement, Maria G; Albertini, Mariangela

    2008-11-01

    We studied the protection of recombinant human activated protein C (rhAPC) in endotoxin-induced lung inflammation and injury and whether this effect is correlated with modulation of lung matrix metalloproteinase (MMP) activity. We randomly assigned 12 Large White pigs to receive intravenous Escher-ichia coli lipopolysaccharide (LPS; 40 mu g/kg/hr), rhAPC (24 mu g/ kg/hr), or both. We monitored respiratory mechanics and function, cell counts, and cytokine concentrations in bron-choalveolar lavage fluid (BALF). Lung samples were collected for the zymography of MMP-2 and MMP-9 activities and for histology. In septic pigs, rhAPC decreased proMMP-9 release as well as MMP-9 activation, and increased proMMP-2 presence without any evident activation compared with specimens that were given LPS alone. In addition, lung injury in rhAPC-treated animals was significantly attenuated, as shown by higher respiratory compliance, delayed increase in tumor necrosis alfa and interleukin-1beta as well as neutrophil recruitment in the BALF, reduced lung edema, and histologic changes. In conclusion, rhAPC is beneficial in acute lung injury, and the protection may depend, at least in part, on modulation of MMP-2/9 activity.

  17. Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.

    Directory of Open Access Journals (Sweden)

    Diego C Reino

    Full Text Available Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI and multiple organ dysfunction syndrome (MODS. Since Toll-like receptors (TLR act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS mediate gut-induced lung injury via TLR4 activation.The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT mice induced lung injury. Using C3H/HeJ mice that harbor a TLR4 mutation, we found that TLR4 activation was necessary for the development of T/HS porcine lymph-induced lung injury as determined by Evan's blue dye (EBD lung permeability and myeloperoxidase (MPO levels as well as the induction of the injurious pulmonary iNOS response. TRIF and Myd88 deficiency fully and partially attenuated T/HS lymph-induced increases in lung permeability respectively. Additional studies in TLR2 deficient mice showed that TLR2 activation was not involved in the pathology of T/HS lymph-induced lung injury. Lastly, the lymph samples were devoid of bacteria, endotoxin and bacterial DNA and passage of lymph through an endotoxin removal column did not abrogate the ability of T/HS lymph to cause lung injury in naïve mice.Our findings suggest that non-microbial factors in the intestinal mesenteric lymph after T/HS are capable of recreating T/HS-induced lung injury via TLR4 activation.

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

    Institute of Scientific and Technical Information of China (English)

    Roland; Andersson

    2010-01-01

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

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

    Science.gov (United States)

    1996-10-01

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

  20. BN 52021 (a platelet activating factor-receptor antagonist decreases alveolar macrophage-mediated lung injury in experimental extrinsic allergic alveolitis

    Directory of Open Access Journals (Sweden)

    J-L. Pérez-Arellano

    1998-01-01

    Full Text Available Several lines of research indirectly suggest that platelet activating factor (PAF may intervene in the pathogenesis of extrinsic allergic alveolitis (EAA. The specific aim of our study was to evaluate the participation of PAF on macrophage activation during the acute phase of EAA in an experimental model of this disease developed in guinea pigs. Initially we measured the concentration of PAF in bronchoalvedar lavage fluid, blood and lung tissue. In a second phase we evaluate the participation of PAF on alveolar macrophage activation and parenchymal lung injury. The effect of PAF on parenchymal lung injury was evaluated by m easuring several lung parenchymatous lesion indices (lung index, bronchoalvedar lavage fluid (BALF lactic hydrogenase activity and BALF alkaline phosphatase activity and parameters of systemic response to the challenge (acute phase reagents. We observed that induction of the experimental EAA gave rise to an increase in the concentration of PAF in blood and in lung tissue. The use of the PAF-receptor antagonist BN52021 decreases the release of lysosomal enzymes (β-glucuronidase and tartrate-sensitive acid phosphatase to the extracellular environment both in vivo and in vitro. Furthermore, antagonism of the PAF receptors notably decreases pulmonary parenchymatous lesion. These data suggest that lung lesions from acute EAA are partly mediated by local production of PAF.

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

    Science.gov (United States)

    Januszkiewicz, A J; Mayorga, M A

    1994-05-20

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

  2. Nitrogen Dioxide-Induced Acute Lung Injury in Sheep

    Science.gov (United States)

    1994-01-01

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

  3. Protective Role of Cyclooxygenase (COX)-2 in Experimental Lung Injury: Evidence of a Lipoxin A(4)-Mediated Effect.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: Polymorphoneutrophils (PMNs) are activated by inflammatory mediators following splanchnic ischemia\\/reperfusion (I\\/R), potentially injuring organs such as the lung. As a result, some patients develop respiratory failure following abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects against acid aspiration and bacterial instillation via lipoxins, a family of potent anti-inflammatory lipid mediators. We explored the role of COX-2 and lipoxin A(4) in experimental I\\/R-mediated lung injury. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: (1) controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I\\/R group); (3) I\\/R and SC236, a selective COX-2 inhibitor; (4) I\\/R and aspirin; and (5) I\\/R and iloprost, a prostacyclin (PGI(2)) analogue. Lung injury was assessed by wet\\/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)alpha (a hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) were analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed. RESULTS: I\\/R significantly increased tissue MPO, the wet\\/dry lung ratio, and neutrophil counts. These measures were significantly further aggravated by SC236 and improved by iloprost. I\\/R increased COX-2 immunostaining and both PGE(2) and 6-keto-PGF(1alpha) levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A(4) compared with I\\/R alone. Iloprost markedly increased lipoxin A(4) levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A(4) levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of COX-2 regulated lung protection.

  4. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion.

    Science.gov (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling

    2012-02-01

    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  5. Estrogen receptor hormone agonists limit trauma hemorrhage shock-induced gut and lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Danielle Doucet

    Full Text Available BACKGROUND: Acute lung injury (ALI and the development of the multiple organ dysfunction syndrome (MODS is a major cause of death in trauma patients. Earlier studies in trauma hemorrhagic shock (T/HS have documented that splanchnic ischemia leading to gut inflammation and loss of barrier function is an initial triggering event that leads to gut-induced ARDS and MODS. Since sex hormones have been shown to modulate the response to T/HS and proestrous (PE females are more resistant to T/HS-induced gut and distant organ injury, the goal of our study was to determine the contribution of estrogen receptor (ERalpha and ERbeta in modulating the protective response of female rats to T/HS-induced gut and lung injury. METHODS/PRINCIPAL FINDINGS: The incidence of gut and lung injury was assessed in PE and ovariectomized (OVX female rats subjected to T/HS or trauma sham shock (T/SS as well as OVX rats that were administered estradiol (E2 or agonists for ERalpha or ERbeta immediately prior to resuscitation. Marked gut and lung injury was observed in OVX rats subjected to T/HS as compared to PE rats or E2-treated OVX rats subjected to T/HS. Both ERalpha and ERbeta agonists were equally effective in limiting T/HS-induced morphologic villous injury and bacterial translocation, whereas the ERbeta agonist was more effective than the ERalpha agonist in limiting T/HS-induced lung injury as determined by histology, Evan's blue lung permeability, bronchoalevolar fluid/plasma protein ratio and myeloperoxidase levels. Similarly, treatment with either E2 or the ERbeta agonist attenuated the induction of the intestinal iNOS response in OVX rats subjected to T/HS whereas the ERalpha agonist was only partially protective. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that estrogen attenuates T/HS-induced gut and lung injury and that its protective effects are mediated by the activation of ERalpha, ERbeta or both receptors.

  6. Toll-like receptor 4 dependent responses to lung injury in a murine model of pulmonary contusion

    OpenAIRE

    2009-01-01

    Blunt chest trauma resulting in pulmonary contusion with an accompanying acute inflammatory response is a common but poorly understood injury. We previously demonstrated that toll-like receptor 2 participates in the inflammatory response to lung injury. We hypothesized that the toll-like receptor 4, in a MyD88-dependent manner, may also participate in the response to lung injury. To investigate this, we used a model of pulmonary contusion in the mouse that is similar to that observed clinical...

  7. Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung injury following inhalation exposure to nerve agent VX.

    Science.gov (United States)

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

    2006-06-01

    Respiratory disturbances play a central role in chemical warfare nerve agent (CWNA) induced toxicity; they are the starting point of mass casualty and the major cause of death. We developed a microinstillation technique of inhalation exposure to nerve agent VX and assessed lung injury by biochemical analysis of the bronchoalveolar lavage fluid (BALF). Here we demonstrate that normal guinea pig BALF has a significant amount of cholinesterase activity. Treatment with Huperzine A, a specific inhibitor of acetylcholinesterase (AChE), showed that a minor fraction of BALF cholinesterase is AChE. Furthermore, treatment with tetraisopropyl pyrophosphoramide (iso-OMPA), a specific inhibitor of butyrylcholinesterase (BChE), inhibited more than 90% of BChE activity, indicating the predominance of BChE in BALF. A predominance of BChE expression in the lung lavage was seen in both genders. Substrate specific inhibition indicated that nearly 30% of the cholinesterase in lung tissue homogenate is AChE. BALF and lung tissue AChE and BChE activities were strongly inhibited in guinea pigs exposed for 5 min to 70.4 and 90.4 microg/m3 VX and allowed to recover for 15 min. In contrast, BALF AChE activity was increased 63% and 128% and BChE activity was increased 77% and 88% after 24 h of recovery following 5 min inhalation exposure to 70.4 microg/m3 and 90.4 mg/m3 VX, respectively. The increase in BALF AChE and BChE activity was dose dependent. Since BChE is synthesized in the liver and present in the plasma, an increase in BALF indicates endothelial barrier injury and leakage of plasma into lung interstitium. Therefore, a measure of increased levels of AChE and BChE in the lung lavage can be used to determine the chronology of barrier damage as well as the extent of lung injury following exposure to chemical warfare nerve agents.

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  10. Relationship between Notch Receptors and Hyperoxia-induced Lung Injury in Newborn Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate role of Notch1-3 in hyperoxia-induced lung injury in newborn rat exposed to 85% O2, SD rat litters born on the 22th day were randomly divided into two groups: room air group and hyperoxia group. The animals were sacrificed 1, 4, 7, 10, 14 and 21 days after continued exposure to oxygen (n=40, oxygen>0.85) or room air (n=40). 6 rats each group were used to assess lung histological changes by HE staining and expression of Notch in lungs by immunohistochemistry. Total RNA was extracted by Trizol reagent from frozen lung tissues. Notch mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). Our results showed that 7, 14 and 21 days after O2 exposure, hyperoxia group showed lung injury characterized by pulmonary edema, hemorrhage and lung development arrest. Positive staining for Notch1,Notch 2 in hyperoxia group was much lower than those in room air group at all time points (P<0.01, P<0.05), but compared with the controls, the hyperoxia group showed higher expression of Notch3 (P>0.05). Immunostained cells were typically airways epithelia, alveolar epithelial and inflammatory cells, and fibroblasts in hyperoxia group (P<0.01). Notch mRNA levels showed similar change as protein level (P< 0.01). It is concluded that the prolonged exposure to 85 % O2 resulted in abnormal expression of Notch receptors, which might contribute to the pathogenesis of hyperoxia-induced lung injury in newborn rats. The decreased inhibition of Notch1 might be one of the protective reaction and major mechanisms for proliferation/differentiation of type Ⅱ alveolar epithelial cells. The up-regulation of Notch3 activity might result in the lung development arrest of the newborn rats.

  11. Edaravone attenuates ischemia-reperfusion injury by inhibiting oxidative stress in a canine lung transplantation model

    Institute of Scientific and Technical Information of China (English)

    XU Jin-zhi; SHEN Bao-zhong; LI Ye; ZHANG Tong; XU Wan-hai; LIU Xiao-wei; LU Hong-guang

    2008-01-01

    Background Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion(IR) injury of many organs.In this study,we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model. Methods Twelve weight-matched pairs of random-bred dogs were randomized into two groups.Within each pair,one dog served as donor and the other as recipient.In the study group,prostaglandin EI(PGEl)(8 μg/kg)was injected into the donor pulmonary artery(PA)before occlusion and the donor lungs were flushed with 1.0L of LPD solution containing edaravone(10mg/kg)and stored in the same LPD solution at a temperature of 1.C for 8 hours.The left single lung transplantation was then performed and recipients received intravenous injection with edaravone l 1 0 mg/kg)at the onset of reperfusion.In the control group,edaravone was substituted by the same volume of sterile saline solution.Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury.One hour after repeffusion.or after dissection of the left lung,the right lung was excluded from peffusion and ventilation after which,cardiopulmonary parameters were measured.Wet/dry ratios,malondiaIdehyde(MDA)and myeloperoxidase (MPO)levels were assessed and histological analysis of lung tissue performed at the same time.Results All animals survived until the end of the experiment.The study group showed significantly decreased wet/dry ratios(treated:(74.1±4.2)%vs control:(86.8±5.2)%,P<0.01),MDA levels(treated:0.50±0.08 vs control:0.88±0.15,P <0.01)and MPO activity(treated:0.23±0.05 vs control:0.43±0.07,P

  12. Lung injury after cigarette smoking is particle-related

    Science.gov (United States)

    That specific component responsible and the mechanistic pathway for increased human morbidity and mortality after cigarette smoking have yet to be delineated. We propose that 1) injury and disease following cigarette smoking are associated with exposure and retention of particles...

  13. TGF-beta, radiation-induced pulmonary Injury and lung cancer

    NARCIS (Netherlands)

    Vujaskovic, Z; Groen, HJM

    2000-01-01

    Purpose: To determine whether changes in TGF-beta plasma levels during radiation therapy may be useful in predicting radiation-induced pulmonary injury and tumour response in non-small-cell lung cancer (NSCLC) patients. Materials and methods: Plasma TGF-beta was investigated in 27 patients with stag

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

    NARCIS (Netherlands)

    Bern, R.A.

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    刘学民; 刘青光; 潘承恩

    2002-01-01

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

  18. Complement activation contributes to ventilator-induced lung injury in rats

    NARCIS (Netherlands)

    B. Petersen; T. Busch; J. Gaertner; J.J. Haitsma (Jack); S.C. Krabbendam (Stefan); M. Ebsen (Michael); B.F. Lachmann (Burkhard); U.X. Kaisers

    2016-01-01

    textabstractThe complement system contributes to ventilator induced lung injury (VILI). We hypothesized that pretreatment with the C1 esterase inhibitor (C1INH) Berinert® constrains complement activation consecutively inducing improvements in arterial oxygenation and histological pulmonary damage. A

  19. Mechanisms and consequences of lung epithelial injury in severe RSV disease

    NARCIS (Netherlands)

    van den Berg, E.

    2015-01-01

    The studies in this thesis have examined mechanisms and consequences of lung epithelial injury in severe RSV disease. In this context, they specifically contribute to the knowledge of apoptosis and the formation of pulmonary edema. The results of our studies underscore the complexity of the mechanis

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

    OpenAIRE

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

    2008-01-01

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

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

    Lifescience Database Archive (English)

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

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

    NARCIS (Netherlands)

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

    1995-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Roger G SPRAGG

    2003-01-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  6. Biomarkers of asbestos-induced lung injury: the influence of fiber characteristics and exposure methodology

    Science.gov (United States)

    ATS 2013 Biomarkers of asbestos-induced lung injury: the influence of fiber characteristics and exposure methodology Urmila P Kodavanti, Debora Andrews, Mette C Schaldweiler, Jaime M Cyphert, Darol E Dodd, and Stephen H Gavett NHEERL, U.S. EPA, Research Triangle Park, NC; NIEH...

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

    Science.gov (United States)

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

    2003-03-01

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

  8. Smart imaging of acute lung injury: exploration of myeloperoxidase activity using in vivo endoscopic confocal fluorescence microscopy.

    Science.gov (United States)

    Chagnon, Frédéric; Bourgouin, Alexandra; Lebel, Réjean; Bonin, Marc-André; Marsault, Eric; Lepage, Martin; Lesur, Olivier

    2015-09-15

    The pathophysiology of acute lung injury (ALI) is well characterized, but its real-time assessment at bedside remains a challenge. When patients do not improve after 1 wk despite supportive therapies, physicians have to consider open lung biopsy (OLB) to identify the process(es) at play. Sustained inflammation and inadequate repair are often observed in this context. OLB is neither easy to perform in a critical setting nor exempt from complications. Herein, we explore intravital endoscopic confocal fluorescence microscopy (ECFM) of the lung in vivo combined with the use of fluorescent smart probe(s) activated by myeloperoxidase (MPO). MPO is a granular enzyme expressed by polymorphonuclear neutrophils (PMNs) and alveolar macrophages (AMs), catalyzing the synthesis of hypoclorous acid, a by-product of hydrogen peroxide. Activation of these probes was first validated in vitro in relevant cells (i.e., AMs and PMNs) and on MPO-non-expressing cells (as negative controls) and then tested in vivo using three rat models of ALI and real-time intravital imaging with ECFM. Semiquantitative image analyses revealed that in vivo probe-related cellular/background fluorescence was associated with corresponding enhanced lung enzymatic activity and was partly prevented by specific MPO inhibition. Additional ex vivo phenotyping was performed, confirming that fluorescent cells were neutrophil elastase(+) (PMNs) or CD68(+) (AMs). This work is a first step toward "virtual biopsy" of ALI without OLB.

  9. Indium oxide (In2O3) nanoparticles induce progressive lung injury distinct from lung injuries by copper oxide (CuO) and nickel oxide (NiO) nanoparticles.

    Science.gov (United States)

    Jeong, Jiyoung; Kim, Jeongeun; Seok, Seung Hyeok; Cho, Wan-Seob

    2016-04-01

    Indium is an essential element in the manufacture of liquid crystal displays and other electronic devices, and several forms of indium compounds have been developed, including nanopowders, films, nanowires, and indium metal complexes. Although there are several reports on lung injury caused by indium-containing compounds, the toxicity of nanoscale indium oxide (In2O3) particles has not been reported. Here, we compared lung injury induced by a single exposure to In2O3 nanoparticles (NPs) to that caused by benchmark high-toxicity nickel oxide (NiO) and copper oxide (CuO) NPs. In2O3 NPs at doses of 7.5, 30, and 90 cm(2)/rat (50, 200, and 600 µg/rat) were administered to 6-week-old female Wistar rats via pharyngeal aspiration, and lung inflammation was evaluated 1, 3, 14, and 28 days after treatment. Neutrophilic inflammation was observed on day 1 and worsened until day 28, and severe pulmonary alveolar proteinosis (PAP) was observed on post-aspiration days 14 and 28. In contrast, pharyngeal aspiration of NiO NPs showed severe neutrophilic inflammation on day 1 and lymphocytic inflammation with PAP on day 28. Pharyngeal aspiration of CuO NPs showed severe neutrophilic inflammation on day 1, but symptoms were completely resolved after 14 days and no PAP was observed. The dose of In2O3 NPs that produced progressive neutrophilic inflammation and PAP was much less than the doses of other toxic particles that produced this effect, including crystalline silica and NiO NPs. These results suggest that occupational exposure to In2O3 NPs can cause severe lung injury.

  10. [Advances in the study of the relationship between autophagy and sepsis-induced lung injury].

    Science.gov (United States)

    Wang, Xingtong; Li, Hengyu; Xia, Zhaofan

    2014-08-01

    Sepsis is one of the most common pathogenetic causes of acute lung injury (ALI), and at present there is still a lack of effective targeted techniques and methods for its prevention and treatment. Autophagy is a homeostatic mecha- nism common to all eukaryotic cells, including adaption to environment, defense against invasion of pathogens, and maintenance of cellular homeostasis. Autophagy is also involved in a variety of lung-related diseases. In septic lung injury, autophagy not only serves to dissipate dysfunctional organelles, but also inhibits the release of inflammatory cytokines. This review aims at eliciting the role of autophagy in sepsis-induced ALI and further exploring the potential targets of autophagy in inhibiting inflammation, in an effort to provide a new perspective for clinical treatment of sepsis-induced ALI.

  11. Effect of Sodium Ferulate on Fluidity and Morphology of Cell Membrane in Ozone Induced Lung Injury

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To study the effect of sodium ferulate (SF), an active component of Radix Angelica, on lung damage induced by ozone (O3). Methods: Mice model of lung injury was induced by ozone inhalation and treated with SF. The level of lipid peroxide and microviscosity in alveolar epithelial cell membrane of the mice was determined, and the structural change of lung cells was observed by microscopy. Results: Ozone could increase the level of malondialdehyde (MDA) and the microviscosity in alveolar epithelial cell membrane, and induce inflammatory changes in morphologic structure. These abnormal changes were improved after SF administration, which was manifested as alleviation of heightened microviscosity, increase of membrane fluidity, as well as the basically normalized pulmonary cellular structure under microscope. Conclusion: SF has a preventive effect against oxidized pulmonary injury induced by ozone, the action of which could be through scavenging oxygen free radicals, reducing lipid peroxide production, increasing membranous fluidity and mitigating inflammatory changes in cell structure.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  13. Aging promotes pro-fibrotic matrix production and increases fibrocyte recruitment during acute lung injury.

    Science.gov (United States)

    Sueblinvong, Viranuj; Neveu, Wendy A; Neujahr, David C; Mills, Stephen T; Rojas, Mauricio; Roman, Jesse; Guidot, David M

    2014-01-01

    Fibrotic lung diseases increase with age. Previously we determined that senescence increases tissue expression of fibronectin EDA (Fn-EDA) and decreases fibroblast expression of Thy-1, and that fibrocytes contribute to fibrosis following bleomycin-induced lung injury in mice. In this study we hypothesized that fibroblasts lacking Thy-1 expression produce an extracellular matrix that promotes fibrocyte retention and myofibroblast transdifferentiation, thereby promoting fibrogenesis. Young and old mice were treated with bleomycin intratracheally; fibrocytes in the bone marrow, blood, and lungs were quantified, and lung fibroblast Thy-1 expression assessed. Bone marrow-derived fibrocytes were cultured on matrices derived from Thy-1(+) or Thy-1(-) fibroblasts ± the pro-fibrotic cytokine TGFβ1. Older mice had more fibrocytes in their bone marrows at baseline and more fibrocytes in their lungs following bleomycin treatment. In parallel, lung fibroblasts in older mice had lower expression of Thy-1 at baseline that increased transiently 7 days after bleomycin treatment but then rapidly waned such that 14 days after bleomycin treatment Thy-1 expression was again markedly lower. Fibrocytes cultured on matrices derived from Thy-1(-) fibroblasts + TGFβ1 had increased gene expression for collagen type 1, fibronectin, Fn-EDA, and α-smooth muscle actin. In parallel, whereas the matrices derived from Thy-1(-) fibroblasts stimulated phosphorylation of Akt in cultured fibrocytes, the matrices derived from Thy-1(+) fibroblasts induced apoptosis. These findings suggest that senescence increases fibrocyte recruitment to the lung following injury and that loss of Thy-1 expression by lung fibroblasts promotes fibrocyte retention and myofibroblast trans-differentiation that renders the "aging lung" susceptible to fibrosis.

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

    Science.gov (United States)

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

    2016-08-01

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

  15. Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Hyun Jung; Do, Kyung-Hyun; Chae, Eun Jin [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Kim, Hwa Jung [University of Ulsan College of Medicine, Cancer Center, Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul (Korea, Republic of); Song, Joon Seon; Jang, Se Jin [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of); Hong, Sang-Bum; Huh, Jin Won [University of Ulsan College of Medicine, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, En [Inje University Haundae Paik Hospital, Department of Pediatrics, Busan (Korea, Republic of); Hong, Soo-Jong [University of Ulsan College of Medicine, Department of Pediatrics, Childhood Asthma and Atopy Center, Environmental Health Center, Asan Medical Center, Seoul (Korea, Republic of)

    2017-01-15

    To identify clinical and radiologic findings that affect disease severity and short-term prognosis of humidifier disinfectant-associated lung injury in adults and to compare computed tomography (CT) findings between the patients with and without death or lung transplantation. Fifty-nine adults (mean age, 34 years; M/F = 12:47) were enrolled in this retrospective study. Medical records and prospective surveillance data were used to assess clinical and radiological factors associated with a poor clinical outcome. Multivariate generalized estimating equation models were used to analyse serial CT findings. Overall cumulative major events including lung transplantation and mortality were assessed using the Kaplan-Meier method. Almost half needed ICU admission (47.5 %) and 17 died (28.8 %). Young age, peripartum and low O{sub 2} saturation were factors associated with ICU admission. On initial chest radiographs, consolidation (P < 0.001) and ground-glass opacity (P = 0.01) were significantly noted in patients who required ICU admission. CT findings including consolidation (odds ratio (OR), 1.02), pneumomediastinum (OR, 1.66) and pulmonary interstitial emphysema (OR, 1.61) were the risk factors for lung transplantation and mortality. Clinical and radiologic findings are related to the risks of lung transplantation and mortality of humidifier disinfectant-associated lung injury. Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. (orig.)

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2012-09-15

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

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

    Directory of Open Access Journals (Sweden)

    Faller Simone

    2012-10-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  2. Salvianolic acid B attenuates lung inflammation induced by cigarette smoke in mice.

    Science.gov (United States)

    Zhang, Dong-Fang; Zhang, Jin; Li, Ran

    2015-08-15

    Salvianolic acid B (Sal B), a bioactive compound isolated from the Chinese herb Radix Salviae Miltiorrhizae, has been reported to exhibit anti-inflammatory and anti-oxidantive effects. The aim of this study was to investigate the protective effects of Sal B on cigarette smoke (CS)-induced acute lung inflammation. Sal B was given intraperitoneally (i.p.) to mice 1h before CS exposure daily for four consecutive days. Bronchoalveolar lavage fluid (BALF) was collected to assess the levels of inflammatory cytokines and cell counts. Lung tissues were used to analysis pathological changes, total glutathione (GSH), nuclear factor erythroid-2 related factor 2 (Nrf-2), and nuclear factor-kappa B (NF-κB) expression. The results showed that Sal B inhibited CS-induced lung pathological changes, the infiltration of inflammatory cells, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) productions. Sal B also up-regulated CS-induced total glutathione (GSH) production. Furthermore, Sal B was found to up-regulate Nrf-2, hemeoxygenase1 (HO1) expression and suppress CS-induced NF-κB activation. In conclusion, the current study demonstrated that Sal B exhibited a protective effect on CS-induced lung injury and the possible mechanism was involved in activating Nrf-2 and inhibiting NF-κB activation.

  3. Strategies to improve oxygenation in experimental acute lung injury

    NARCIS (Netherlands)

    A. Hartog (Arthur)

    2000-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  5. Increased intestinal protein permeability in a model of lung injury induced by phorbol myristate acetate.

    Science.gov (United States)

    St John, R C; Mizer, L A; Weisbrode, S E; Dorinsky, P M

    1991-11-01

    Multiple nonpulmonary organ failure is a frequent complication of the adult respiratory distress syndrome (ARDS), and contributes significantly to the high mortality rate associated with this disorder. Although previous studies suggest that systemic organ injury may be an integral component of ARDS, little is known about the specific functional alterations that occur in these target organs. The present study was designed, therefore, to test the hypothesis that endothelial damage, as assessed by microvascular permeability changes, develops in systemic organs in a model of acute lung injury. To test this postulate, the microvascular permeability for total protein was estimated using the steady-state relationship between the lymph (CL) to plasma (Cp) protein concentration ratio (i.e., CL/Cp) and lymph flow in autoperfused cat ileum preparations. Specifically, CL/Cp was measured in five cats, 2 h after acute lung injury was induced by intravenously administered phorbol myristate acetate (PMA), 15 micrograms/kg, and the results were compared with those of seven time-matched control animals. Prior to PMA infusion, the PaO2/FIO2 ratio was 451 +/- 28 in both groups and remained unchanged (486 +/- 26) in the control group. By contrast, the PaO2/FIO2 ratio fell to 275 +/- 95 after PMA infusion (p less than 0.05). In addition, whereas CL/Cp was 0.099 +/- 0.008 in the control animals, it increased to 0.36 +/- 0.06 in the PMA-injured animals (p less than 0.01). In summary, this study demonstrated that in this model of acute lung injury produced by PMA-induced activation of circulating inflammatory cells, both acute lung injury and systemic organ injury (i.e., morphologic and permeability alterations) occurred.

  6. COMPLEX CLINICAL AND INSTRUMENTAL EVALUATION OF LUNG INJURY IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    I. I. Nesterovich

    2016-01-01

    Full Text Available The damage of the respiratory system is a quite common  extra-articular manifestation  of rheumatoid  arthritis (RA. It is important  to note that its clinical symptoms occur in only 20–30% of patients; however, subclinical forms identified by active screening are observed in 70–80% of patients.Objective: to compare the significance of pulmonary complaints,  the results of physical examination, and the data of instrumental  studies for the detection  of lung injury in patients with RA.Subjects and methods. The study enrolled 70 RA patients (63 women and 7 men aged 24 to 83 years. Only 10% of them had clinically evident lung injury associated with RA. Patients with other pulmonary diseases, such as asthma, chronic obstructive pulmonary disease, etc., were excluded. Physical examination, radiography/fluoroscopy, high-resolution computed  tomography (HRCT, single-photon emission computed  tomography (SPECT of the lung, and lung function testing (LFT with the determination of lung diffusion capacity.Results and discussion. The data of physical examination  were nonspecific and unconvincing.  Pulmonary  complaints (dyspnea, cough, expectoration were seen in 65% of the patients; an objective assessment revealed changes (vesiculotympanitic resonance,  harsh breathing, and pleural friction rub in 40%. The X-ray films/fluorograms  displayed abnormalities (pulmonary fibrosis, focal changes in only 10% of cases. 92% of the patients had lung HRCT  changes including moderate (bronchial  obstruction (40%, rheumatoid  nodules (10%, ground glass opacities (60%, bronchial thickening (20%, pleural effusion (10%, tree-in-bud opacities (3% and severe (pulmonary hypertension  (10%, bronchiectasis (10%, emphysema (5% and lung tissue fibrotic changes as the honeycomb lung (2% ones. SPECT showed local hypoperfusion in the mantle and mediastinal parts of the lungs in 80% of cases. LFT analysis demonstrated reduced lung diffusion capacity in 41% of

  7. The Effects of Dexamethasone and L-NAME on Acute Lung Injury in Rats with Lung Contusion.

    Science.gov (United States)

    Kozan, Ahmet; Kilic, Nermin; Alacam, Hasan; Guzel, Ahmet; Guvenc, Tolga; Acikgoz, Mehmet

    2016-10-01

    The therapeutic efficiency of an anti-inflammatory agent, dexamethasone (DXM), and a nitric oxide synthase (NOS) inhibitor, Nitro-L-arginine methyl ester (L-NAME), in lung tissue injury after lung contusion was investigated. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), YKL-40, an inflammatory peptide, inducible NOS (iNOS), and Clara cell protein 16 (CC-16) were evaluated. Immunohistochemical analyses were also performed, and the lung tissue was examined histopathologically. The study consisted of eight groups of Sprague-Dawley rats (n = 10 in each group), weighing 250-300 g: (1) control, (2) contusion, (3) control + DXM, (4) contusion + DXM, (5) control + L-NAME (6) contusion + L-NAME, (7) control + DXM + L-NAME, and (8) contusion + DXM + L-NAME. A previously developed lung contusion model was used, in addition to the control group. The rats were administered DXM and L-NAME intraperitoneally (i.p.) at doses of 15 and 60 mg/kg/day, respectively. DXM and L-NAME administration decreased the iNOS level in the contusion groups. DXM increased the levels of YKL-40 and IL-10 in both the control and contusion groups, with higher levels in the contusion groups. L-NAME increased the serum level of IL-10 in the lung contusion groups. DXM increased the synthesis of CC-16 in the control and contusion groups. The combined use of a high-dose steroid and NOS inhibitor resulted in the death of the rats. Steroids can increase the level of cytokines, such as YKL-40 and IL-10, and the synthesis of CC-16 and prevent pneumonia, ALI/ARDS, and sepsis in lung contusion.

  8. Effects of early bronchoalveolar lavage fluid collected from dogs with smoke inhalation injury on the lungs of rats

    Institute of Scientific and Technical Information of China (English)

    NIE Fa-chuan; SU Dong; YANG Zong-cheng; BI Min; HUANG Yue-sheng

    2004-01-01

    Objective: Whether early massive bronchoalveolar lavage can remove the harmful substances from the lungs injured with smoke inhalation remains uncertain. This study was designed to observe the effects of early massive bronchoalveolar lavage fluid (BALF) on the healthy lungs in rats. Methods: Mongrel dogs were inflicted with severe smoke inhalation injury. The injured lungs were lavaged with large amount of normal saline in the first hour after injury and the BALF was collected. The BALF was injected into the healthy lungs of 30 rats (group C) in the dosage of 5 ml/kg. The functions and pathological changes of the lungs were observed 24 h after perfusion with the BALF. The data were compared with those of 23 rats (group B) whose lungs were perfused with the BALF collected from normal dogs and those of 21 rats (group A)whose lungs were perfused with normal saline. Results: The mortality rate 24 h after lung perfusion was higher in group C than in groups A and B. The survivors of group C exhibited fluctuation of respiratory rate (RR), remarkable decrease of PaO2, significantly higher content of lung water, decrease of total static pulmonary compliance and pulmonary expansion index, and increasse of inflammatory cytokines in the tissues of lungs. Only slight mechanic obstructive effect on the airway was observed in rats of group A and B. The pathological changes of the lungs of the rats in group C were similar to those of the dogs with actual smoke inhalation injury. Conclusion: Our findings indicate that the BALF collected from dogs with acute severe smoke inhalation injury in the early stage after injury injured the normal lungs of rats with the bioactive substances in the BALF. These findings show us that it is a valuable therapeutic procedure to apply massive bronchoalveolar fluid lavage in the early stage after inhalation injury.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  10. Systemic Metabolic Impairment and Lung Injury Following Acrolein Inhalation

    Science.gov (United States)

    A single ozone exposure causes pulmonary injury and systemic metabolic alterations through neuronal and hypothalamus pituitary adrenal axis activation. Metabolically impaired Goto Kakizaki (GK) rats with non-obese type-2 diabetes are more sensitive to ozone induced changes than h...

  11. Sphingosine-1-phosphate receptor 1 agonism attenuates lung ischemia-reperfusion injury

    Science.gov (United States)

    Stone, Matthew L.; Sharma, Ashish K.; Zhao, Yunge; Charles, Eric J.; Huerter, Mary E.; Johnston, William F.; Kron, Irving L.; Lynch, Kevin R.

    2015-01-01

    Outcomes for lung transplantation are the worst of any solid organ, and ischemia-reperfusion injury (IRI) limits both short- and long-term outcomes. Presently no therapeutic agents are available to prevent IRI. Sphingosine 1-phosphate (S1P) modulates immune function through binding to a set of G protein-coupled receptors (S1PR1-5). Although S1P has been shown to attenuate lung IRI, the S1P receptors responsible for protection have not been defined. The present study tests the hypothesis that protection from lung IRI is primarily mediated through S1PR1 activation. Mice were treated with either vehicle, FTY720 (a nonselective S1P receptor agonist), or VPC01091 (a selective S1PR1 agonist and S1PR3 antagonist) before left lung IR. Function, vascular permeability, cytokine expression, neutrophil infiltration, and myeloperoxidase levels were measured in lungs. After IR, both FTY720 and VPC01091 significantly improved lung function (reduced pulmonary artery pressure and increased pulmonary compliance) vs. vehicle control. In addition, FTY720 and VPC01091 significantly reduced vascular permeability, expression of proinflammatory cytokines (IL-6, IL-17, IL-12/IL-23 p40, CC chemokine ligand-2, and TNF-α), myeloperoxidase levels, and neutrophil infiltration compared with control. No significant differences were observed between VPC01091 and FTY720 treatment groups. VPC01091 did not significantly affect elevated invariant natural killer T cell infiltration after IR, and administration of an S1PR1 antagonist reversed VPC01091-mediated protection after IR. In conclusion, VPC01091 and FTY720 provide comparable protection from lung injury and dysfunction after IR. These findings suggest that S1P-mediated protection from IRI is mediated by S1PR1 activation, independent of S1PR3, and that selective S1PR1 agonists may provide a novel therapeutic strategy to prevent lung IRI. PMID:25910934

  12. Recurrent recruitment manoeuvres improve lung mechanics and minimize lung injury during mechanical ventilation of healthy mice.

    Directory of Open Access Journals (Sweden)

    Lucy Kathleen Reiss

    Full Text Available INTRODUCTION: Mechanical ventilation (MV of mice is increasingly required in experimental studies, but the conditions that allow stable ventilation of mice over several hours have not yet been fully defined. In addition, most previous studies documented vital parameters and lung mechanics only incompletely. The aim of the present study was to establish experimental conditions that keep these parameters within their physiological range over a period of 6 h. For this purpose, we also examined the effects of frequent short recruitment manoeuvres (RM in healthy mice. METHODS: Mice were ventilated at low tidal volume V(T = 8 mL/kg or high tidal volume V(T = 16 mL/kg and a positive end-expiratory pressure (PEEP of 2 or 6 cm H(2O. RM were performed every 5 min, 60 min or not at all. Lung mechanics were followed by the forced oscillation technique. Blood pressure (BP, electrocardiogram (ECG, heart frequency (HF, oxygen saturation and body temperature were monitored. Blood gases, neutrophil-recruitment, microvascular permeability and pro-inflammatory cytokines in bronchoalveolar lavage (BAL and blood serum as well as histopathology of the lung were examined. RESULTS: MV with repetitive RM every 5 min resulted in stable respiratory mechanics. Ventilation without RM worsened lung mechanics due to alveolar collapse, leading to impaired gas exchange. HF and BP were affected by anaesthesia, but not by ventilation. Microvascular permeability was highest in atelectatic lungs, whereas neutrophil-recruitment and structural changes were strongest in lungs ventilated with high tidal volume. The cytokines IL-6 and KC, but neither TNF nor IP-10, were elevated in the BAL and serum of all ventilated mice and were reduced by recurrent RM. Lung mechanics, oxygenation and pulmonary inflammation were improved by increased PEEP. CONCLUSIONS: Recurrent RM maintain lung mechanics in their physiological range during low tidal volume ventilation of healthy mice by

  13. Severe lung injuries due to SO/sub 2/ inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Wunderlich, P.; Leupold, W.; Mittenzwey, K.W.; Rupprecht, E.

    1982-01-01

    By accident a 12 year old boy had to spend 4 hours in a SO/sub 2/-enriched atmosphere (concentration 13.8 mg per cubicmeter = 4.8 ppm). The course of the following intoxication was tetraphasic: 1. acute irritation of the mucous membranes of the upper airways and of the eye: rhinopharyngitis, laryngitis and bronchitis, conjunctivitis and corneal lesions (duration: 5 days), 2. symptom free interval (duration: 3 days), 3. subacute destruction of the low airways and the lung: destructing bronchitis, bronchiolitis, alveolitis, emphysema of the lung, mediastinum and skin, gradual development of bronchiectasis (duration: 9-12 months) and 4. gradual transition into terminal scarification: emphysema of the lung, continuous partial respiratory insufficiency with combined, especially obstructive disturbance of ventilation (without alterations observed during the last 4 years). On occasions of this fateful and therapeutically hardly influenced course recommendations are given for initial general and topical administration of very high doses of corticosteroids in each case of inhalative intoxication as the only measure which probably would have prevented it.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-05

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

  15. Antioxidant effects of selenium on lung injury in paraquat intoxicated rats

    Science.gov (United States)

    Kim, K.S.; Suh, G.J.; Kwon, W.Y.; Kwak, Y.H.; Lee, Kenneth; Lee, H.J.; Jeong, K.Y.; Lee, M.W.

    2012-01-01

    CONTEXT: Paraquat (PQ) causes lethal intoxication by inducing oxidant injury to the lung. Selenium is a cofactor for glutathione peroxidase (GPx), which is one of the major endogenous antioxidant enzymes. OBJECTIVE: To determine whether selenium post-treatment activates GPx, decreases lung injury, and improves survival in PQ intoxicated rats. MATERIALS AND METHODS: Male Spraque-Dawley rats were categorized into three groups: sham (n = 6), PQ (n = 12), and PQ + Se (n = 12). In the PQ and PQ + Se groups, 50 mg/kg of PQ was administered intraperitoneally. After 10 minutes, 60 μg/kg of Se (PQ + Se) or saline (PQ) was administered via the tail vein. Six rats per group were euthanized 6 hours or 24 hours later. Lung tissues were harvested for the measurement of GPx activity, reduced glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) and for histological analysis. Using separated set of rats, survival of PQ (n = 10) and PQ + Se (n = 10) were observed for 72 hours. RESULTS: GPx activity in the PQ group at the 6-hour and 24-hour time points was lower than in the sham group (p CONCLUSION: Single dose of selenium post-treatment activates GPx and attenuates lipid peroxidation and lung injury early after paraquat intoxication, but does not improve 72 hours of survival.

  16. Expression of aquaporin-1 and aquaporin-3 in lung tissue of rat model with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    ZHAO Song; LI Xiang-nan

    2010-01-01

    @@ End-stage lung diseases are common and frequentlyoccurring diseases which are difficult for clinical treatment. In recent years, lung transplantation has become a widely accepted and effective therapeutic option for patients with the end-stage pulmonary diseases. Early pulmonary edema resulting from ischemia-reperfusion injury accounts for the major part of mortality and morbidity after lung transplantation. The water channel proteins in lung injury have been little studied, and their impact on the formation of pulmonary edema remains unclear. In this study, we established a rat lung ischemia-reperfusion model to study its impact on the expressions of water channel proteins in lung tissue and explore a new approach to lung transplantation in pulmonary edema pathogenesis.

  17. Protective effect of ginsenoside Rg1 on glutamate-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    Li SHEN; Jian-zhong HAN; Chen LI; Shao-jie YUE; Yong LIU; Xiao-qun QIN; Hui-jun LIU; Zi-qiang LUO

    2007-01-01

    Aim: To examine the possible protective effect of ginsenoside Rg1, an active component of ginseng, on lung injury caused by glutamate in vivo. Methods: The lungs of mice receiving glutamate (0.5 g/kg) and/or ginsenoside Rg1 (0.03 g/kg) via intraperitoneal administration were collected. The indexes of lung wet weight/body weight ratios (LW/BW), lung wet/dry weight ratios (W/D), heart rate (HR),and breathing rate (BR) were determined. The activity of nitric oxide synthase(NOS), xanthine oxidase (XOD), superoxide dismutase (SOD), catalase (CAT), the content of NO, and malondialdehyde in the lung homogenate were measured.Results: Treatment with glutamate for 2 h increased LW/BW, W/D, HR, and BR.These changes were nearly abolished by pretreatment with ginsenoside Rg1 for 30 min before glutamate injection. An analysis of the lung homogenate demon-strated the protective effect as evidenced by the inhibition of NOS (12%) and XOD (50%) inactivity, the enhanced activity of SOD (20%) and CAT (25%).Conclusion: Ginsenoside Rg1 has a potential protective role in lung diseases associated with glutamate toxicity.

  18. Activation of nicotinic cholinergic receptors prevents ventilator-induced lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Fabienne Brégeon

    Full Text Available Respiratory distress syndrome is responsible for 40 to 60 percent mortality. An over mortality of about 10 percent could result from additional lung injury and inflammation due to the life-support mechanical ventilation, which stretches the lung. It has been recently demonstrated, in vitro, that pharmacological activation of the alpha 7 nicotinic receptors (α7-nAChR could down regulate intracellular mediators involved in lung cell inflammatory response to stretch. Our aim was to test in vivo the protective effect of the pharmacological activation of the α7-nAChR against ventilator-induced lung injury (VILI. Anesthetized rats were ventilated for two hours with a high stretch ventilation mode delivering a stroke volume large enough to generate 25-cmH(2O airway pressure, and randomly assigned to four groups: pretreated with parenteral injection of saline or specific agonist of the α7-nAChR (PNU-282987, or submitted to bilateral vagus nerve electrostimulation while pre-treated or not with the α7-nAChR antagonist methyllycaconitine (MLA. Controls ventilated with a conventional stroke volume of 10 mL/kg gave reference data. Physiological indices (compliance of the respiratory system, lung weight, blood oxygenation, arterial blood pressure and lung contents of inflammatory mediators (IL-6 measured by ELISA, substance P assessed using HPLC were severely impaired after two hours of high stretch ventilation (sham group. Vagal stimulation was able to maintain the respiratory parameters close to those obtained in Controls and reduced lung inflammation except when associated to nicotinic receptor blockade (MLA, suggesting the involvement of α7-nAChR in vagally-mediated protection against VILI. Pharmacological pre-treatment with PNU-282987 strongly decreased lung injury and lung IL-6 and substance P contents, and nearly abolished the increase in plasmatic IL-6 levels. Pathological examination of the lungs confirmed the physiological differences observed

  19. Targeted Type 2 Alveolar Cell Depletion. A Dynamic Functional Model for Lung Injury Repair.

    Science.gov (United States)

    Garcia, Orquidea; Hiatt, Michael J; Lundin, Amber; Lee, Jooeun; Reddy, Raghava; Navarro, Sonia; Kikuchi, Alex; Driscoll, Barbara

    2016-03-01

    Type 2 alveolar epithelial cells (AEC2) are regarded as the progenitor population of the alveolus responsible for injury repair and homeostatic maintenance. Depletion of this population is hypothesized to underlie various lung pathologies. Current models of lung injury rely on either uncontrolled, nonspecific destruction of alveolar epithelia or on targeted, nontitratable levels of fixed AEC2 ablation. We hypothesized that discrete levels of AEC2 ablation would trigger stereotypical and informative patterns of repair. To this end, we created a transgenic mouse model in which the surfactant protein-C promoter drives expression of a mutant SR39TK herpes simplex virus-1 thymidine kinase specifically in AEC2. Because of the sensitivity of SR39TK, low doses of ganciclovir can be administered to these animals to induce dose-dependent AEC2 depletion ranging from mild (50%) to lethal (82%) levels. We demonstrate that specific levels of AEC2 depletion cause altered expression patterns of apoptosis and repair proteins in surviving AEC2 as well as distinct changes in distal lung morphology, pulmonary function, collagen deposition, and expression of remodeling proteins in whole lung that persist for up to 60 days. We believe SPCTK mice demonstrate the utility of cell-specific expression of the SR39TK transgene for exerting fine control of target cell depletion. Our data demonstrate, for the first time, that specific levels of type 2 alveolar epithelial cell depletion produce characteristic injury repair outcomes. Most importantly, use of these mice will contribute to a better understanding of the role of AEC2 in the initiation of, and response to, lung injury.

  20. Inflammation and lung maturation from stretch injury in preterm fetal sheep.

    Science.gov (United States)

    Hillman, Noah H; Polglase, Graeme R; Pillow, J Jane; Saito, Masatoshi; Kallapur, Suhas G; Jobe, Alan H

    2011-02-01

    Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (V(T)) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury. After maternal anesthesia and hysterotomy, 129-day gestation fetal lambs (n = 7-8/group) had the head and chest exteriorized. Each fetus was intubated, and airway fluid was gently removed. While placental support was maintained, the fetus received ventilation with an escalating V(T) to 15 ml/kg without positive end-expiratory pressure (PEEP) for 15 min using heated, humidified 100% nitrogen. The fetus was then returned to the uterus for 1, 6, or 24 h. Control lambs received a PEEP of 2 cmH(2)O for 15 min. Tissue samples from the lung and systemic organs were evaluated. Stretch injury increased the early response gene Egr-1 and increased expression of pro- and anti-inflammatory cytokines within 1 h. The injury induced granulocyte/macrophage colony-stimulating factor mRNA and matured monocytes to alveolar macrophages by 24 h. The mRNA for the surfactant proteins A, B, and C increased in the lungs by 24 h. The airway epithelium demonstrated dynamic changes in heat shock protein 70 (HSP70) over time. Serum cortisol levels did not increase, and induction of systemic inflammation was minimal. We conclude that a brief period of high V(T) ventilation causes a proinflammatory cascade, a maturation of lung monocytic cells, and an induction of surfactant protein mRNA.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  2. Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Erer D

    2016-08-01

    Full Text Available Dilek Erer,1,* Abdullah Özer,1,* Hüseyin Demirtaş,1 İpek Işık Gönül,2 Halil Kara,3 Hande Arpacı,4 Faruk Metin Çomu,5 Gürsel Levent Oktar,1 Mustafa Arslan,6 Ayşegül Küçük7 1Department of Cardiovascular Surgery, 2Department of Pathology, Gazi University Medical Faculty, 3Department of Pharmacology, Yıldırım Beyazıt University Medical Faculty, 4Department of Oral and Maxillofacial Surgery, Ankara University Faculty of Dentistry, Besevler, Ankara, 5Department of Physiology, Kırıkkale University Medical Faculty, Kırıkkale, 6Department of Anesthesiology and Reanimation, Gazi University Medical Faculty, Ankara, 7Department of Physiology, Dumlupınar University Medical Faculty, Kütahya, Turkey *These authors contributed equally to this work Objectives: To evaluate the effects of alprostadil (prostaglandin [PGE1] analog and iloprost (prostacyclin [PGI2] analog on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R injury in an experimental rat model.Materials and methods: Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius tissue specimens were examined.Results: Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (P<0.0001, P=0.015, and P<0.01, respectively. Polymorphonuclear leukocyte infiltration, pulmonary partial destruction, consolidation, alveolar edema, and hemorrhage scores were significantly lower in alprostadil- and iloprost-treated groups (P=0.017 and P=0.001; P<0.01 and P<0.0001. Polymorphonuclear leukocyte infiltration scores in skeletal muscle tissue were significantly lower in the iloprost-treated group than the scores found in the nontreated I

  3. Genetic targets of hydrogen sulfide in ventilator-induced lung injury--a microarray study.

    Directory of Open Access Journals (Sweden)

    Sashko Spassov

    Full Text Available Recently, we have shown that inhalation of hydrogen sulfide (H2S protects against ventilator-induced lung injury (VILI. In the present study, we aimed to determine the underlying molecular mechanisms of H2S-dependent lung protection by analyzing gene expression profiles in mice. C57BL/6 mice were subjected to spontaneous breathing or mechanical ventilation in the absence or presence of H2S (80 parts per million. Gene expression profiles were determined by microarray, sqRT-PCR and Western Blot analyses. The association of Atf3 in protection against VILI was confirmed with a Vivo-Morpholino knockout model. Mechanical ventilation caused a significant lung inflammation and damage that was prevented in the presence of H2S. Mechanical ventilation favoured the expression of genes involved in inflammation, leukocyte activation and chemotaxis. In contrast, ventilation with H2S activated genes involved in extracellular matrix remodelling, angiogenesis, inhibition of apoptosis, and inflammation. Amongst others, H2S administration induced Atf3, an anti-inflammatory and anti-apoptotic regulator. Morpholino mediated reduction of Atf3 resulted in elevated lung injury despite the presence of H2S. In conclusion, lung protection by H2S during mechanical ventilation is associated with down-regulation of genes related to oxidative stress and inflammation and up-regulation of anti-apoptotic and anti-inflammatory genes. Here we show that Atf3 is clearly involved in H2S mediated protection.

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

    Directory of Open Access Journals (Sweden)

    Zhongchen Zhang

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

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Xiaomei Feng

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-12-28

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

  9. Role of caveolin-1 expression in the pathogenesis of pulmonary edema in ventilator-induced lung injury

    Science.gov (United States)

    Maniatis, Nikolaos A.; Kardara, Matina; Hecimovich, Dan; Letsiou, Eleftheria; Castellon, Maricela; Roussos, Charalambos; Shinin, Vasily; Votta-Vellis, E. Gina; Schwartz, David E.; Minshall, Richard D.

    2012-01-01

    Caveolin-1 is a key regulator of pulmonary endothelial barrier function. Here, we tested the hypothesis that caveolin-1 expression is required for ventilator-induced lung injury (VILI). Caveolin-1 gene-disrupted (Cav-1-/-) and age-, sex-, and strain-matched wild-type (WT) control mice were ventilated using two protocols: volume-controlled with protective (8 mL/kg) versus injurious (21 mL/Kg) tidal volume for up to 6 hours; and pressure-controlled with protective (airway pressure = 12 cm H2O) versus injurious (30 cm H2O) ventilation to induce lung injury. Lung microvascular permeability (whole-lung 125I-albumin accumulation, lung capillary filtration coefficient [Kf, c]) and inflammatory markers (bronchoalveolar lavage [BAL] cytokine levels and neutrophil counts) were measured. We also evaluated histologic sections from lungs, and the time course of Src kinase activation and caveolin-1 phosphorylation. VILI induced a 1.7-fold increase in lung 125I-albumin accumulation, fourfold increase in Kf, c, significantly increased levels of cytokines CXCL1 and interleukin-6, and promoted BAL neutrophilia in WT mice. Lung injury by these criteria was significantly reduced in Cav-1-/- mice but fully restored by i.v. injection of liposome/Cav-1 cDNA complexes that rescued expression of Cav-1 in lung microvessels. As thrombin is known to play a significant role in mediating stretch-induced vascular injury, we observed in cultured mouse lung microvascular endothelial cells (MLECs) thrombin-induced albumin hyperpermeability and phosphorylation of p44/42 MAP kinase in WT but not in Cav-1-/- MLECs. Thus, caveolin-1 expression is required for mechanical stretch-induced lung inflammation and endothelial hyperpermeability in vitro and in vivo. PMID:23372929

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

    Institute of Scientific and Technical Information of China (English)

    LAN Mei-juan; HE Xiao-di

    2009-01-01

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

  11. Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury

    Science.gov (United States)

    2015-10-01

    patients with severe traumatic injury will determine if the use of tranexamic acid within 2 hours of injury is associated with less immune suppression...forms”, contact information for the study team, links to our Facebook and Twitter pages, feedback forms, our community power point presentation, and...4308 Nearest person month worked 1 Contribution to Project: Dr. Fuchs has developed and validated laboratory techniques associated with the

  12. Ozone Therapy and Hyperbaric Oxygen Treatment in Lung Injury in Septic Rats

    Directory of Open Access Journals (Sweden)

    Levent Yamanel, Umit Kaldirim, Yesim Oztas, Omer Coskun, Yavuz Poyrazoglu, Murat Durusu, Tuncer Cayci, Ahmet Ozturk, Seref Demirbas, Mehmet Yasar, Orhan Cinar, Salim Kemal Tuncer, Yusuf Emrah Eyi, Bulent Uysal, Turgut Topal, Sukru Oter, Ahmet Korkmaz

    2011-01-01

    Full Text Available Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO therapy. It has been shown that ozone therapy (OT reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1β and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1β, lung GSH-Px and histologic outcome.

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

    Science.gov (United States)

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

    2016-12-01

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

  14. p53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis.

    Science.gov (United States)

    Shetty, Shwetha K; Tiwari, Nivedita; Marudamuthu, Amarnath S; Puthusseri, Bijesh; Bhandary, Yashodhar P; Fu, Jian; Levin, Jeffrey; Idell, Steven; Shetty, Sreerama

    2017-03-05

    Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. The pathogenesis of interstitial lung diseases, including its most common form, IPF, remains poorly understood. Alveolar epithelial cell (AEC) apoptosis, proliferation, and accumulation of myofibroblasts and extracellular matrix deposition results in progressive loss of lung function in IPF. We found induction of tumor suppressor protein, p53, and apoptosis with suppression of urokinase-type plasminogen activator (uPA) and the uPA receptor in AECs from the lungs of IPF patients, and in mice with bleomycin, cigarette smoke, silica, or sepsis-induced lung injury. Treatment with the caveolin-1 scaffolding domain peptide (CSP) reversed these effects. Consistent with induction of p53, AECs from IPF lungs or mice with diverse types of lung injuries showed increased p53 acetylation and miR-34a expression with reduction in Sirt1. This was significantly reduced after treatment of wild-type mice with CSP, and uPA-deficient mice were unresponsive. Bleomycin failed to induce miR-34a in p53- or plasminogen activator inhibitor-1 (PAI-1)-deficient mice. CSP-mediated inhibition of miR-34a restored Sirt1, suppressed p53 acetylation and apoptosis in injured AECs, and prevented pulmonary fibrosis (PF). AEC-specific suppression of miR-34a inhibited bleomycin-induced p53, PAI-1, and apoptosis and prevented PF, whereas overexpression of precursor-miR-34a increased p53, PAI-1, and apoptosis in AECs of mice unexposed to bleomycin. Our study validates p53-miR-34a feedback as a potential therapeutic target in PF.

  15. The Protective Effect of Sodium Ferulate and Oxymatrine Combination on Paraquat-induced Lung Injury.

    Science.gov (United States)

    Wang, Wei; Pei, Xiaokun; Xu, Mengxin; Sun, Songmei; Zhang, Chunlei; Mu, Keying; Liu, Zhifeng

    2015-01-01

    Experimental evidence suggested that sodium ferulate (SF) and oxymatrine (OMT) combination had synergistic anti-inflammatory and antioxidant effects. We hypothesized that SF and OMT combination treatment might have protective effects on paraquat-induced acute lung injury. In our study, the Swiss mice were randomly divided into seven groups, including control, paraquat (PQ), SF (6.2 mg/Kg/day); OMT (13.8 mg/Kg/day) and three SF+OMT groups (3.1 + 6.9; 6.2 + 13.8 and 12.3 + 27.7 mg/Kg/day). The mortality and death time were monitored. Sprague-Dawley rats were randomly divided into seven groups including control, PQ, SF (3.1 mg/Kg/day); OMT (6.9 mg/Kg/day) and three SF+OMT groups (1.6 + 3.4; 3.1 + 6.9 and 6.2 + 13.8 mg/Kg/day). The lung wet/dry weight (W/D) ratio, lung histopathologic changes, C-reactive protein (CRP), interleukin-6 (IL-6), nuclear factor κB (NF-κB), malondialdehyde (MDA) and superoxidase dismutase (SOD) were analysed. Compared with PQ group, the mortality significantly decreased and the death time prolonged in SF and OMT combination treatment groups of mice. Also in SF and OMT combination treatment groups of rats, the increased lung W/D ratio and histopathological score induced by PQ injection were significantly decreased; the levels of CRP, IL-6, NF-κB and MDA in serum and lung homogenate were significantly decreased; the SOD activities in serum and lung homogenate were improved. These results suggested that SF and OMT combination had an obvious protective effect on PQ-induced lung injury. The anti-inflammatory and antioxidant effect might be involved in the mechanism.

  16. Bone Marrow-Derived c-kit+ Cells Attenuate Neonatal Hyperoxia-Induced Lung Injury

    Science.gov (United States)

    Ramachandran, Shalini; Suguihara, Cleide; Drummond, Shelley; Chatzistergos, Konstantinos; Klim, Jammie; Torres, Eneida; Huang, Jian; Hehre, Dorothy; Rodrigues, Claudia O.; McNiece, Ian K.; Hare, Joshua M.; Young, Karen C.

    2016-01-01

    Recent studies suggest that bone marrow (BM)-derived stem cells have therapeutic efficacy in neonatal hyperoxia-induced lung injury (HILI). c-kit, a tyrosine kinase receptor that regulates angiogenesis, is expressed on several populations of BM-derived cells. Preterm infants exposed to hyperoxia have decreased lung angiogenesis. Here we tested the hypothesis that administration of BM-derived c-kit+ cells would improve angiogenesis in neonatal rats with HILI. To determine whether intratracheal (IT) administration of BM-derived c-kit+ cells attenuates neonatal HILI, rat pups exposed to either normobaric normoxia (21% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to P15 were randomly assigned to receive either IT BM-derived green fluorescent protein (GFP)+ c-kit− cells (PL) or BM-derived GFP+ c-kit+ cells on P8. The effect of cell therapy on lung angiogenesis, alveolarization, pulmonary hypertension, vascular remodeling, cell proliferation, and apoptosis was determined at P15. Cell engraftment was determined by GFP immunostaining. Compared to PL, the IT administration of BM-derived c-kit+ cells to neonatal rodents with HILI improved alveolarization as evidenced by increased lung septation and decreased mean linear intercept. This was accompanied by an increase in lung vascular density, a decrease in lung apoptosis, and an increase in the secretion of proangiogenic factors. There was no difference in pulmonary vascular remodeling or the degree of pulmonary hypertension. Confocal microscopy demonstrated that 1% of total lung cells were GFP+ cells. IT administration of BM-derived c-kit+ cells improves lung alveolarization and angiogenesis in neonatal HILI, and this may be secondary to an improvement in the lung angiogenic milieu. PMID:23759597

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

    Institute of Scientific and Technical Information of China (English)

    Hsing I Chen

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hodder R

    2012-08-01

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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

    Feng, Xiaosheng; Jia, Aiqing

    2014-08-01

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

  2. The role of alveolar epithelium in radiation-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Celine Almeida

    Full Text Available Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy and fractionated doses (24-36 Gy of (137Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c, the number of pro-SP-c(+ cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.

  3. Immunohistochemical detection of CCR2 and CX3CR1 in sepsis-induced lung injury.

    Science.gov (United States)

    An, Jun-Ling; Ishida, Yuko; Kimura, Akihiko; Tsokos, Michael; Kondo, Toshikazu

    2009-11-20

    Sepsis is a systemic inflammatory disease with high mortality. In the present study, we immunohistochemically examined CCR2 and CX3CR1 expression in sepsis-induced lung injury, and discussed its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48h. Immunohistochemically, mononuclear cells recruited into the lungs expressed CCR2 and CX3CR1 in both sepsis and non-septic groups. In double-color immunofluorescence analysis, CCR2- or CX3CR1-positive cells could be identified as CD68-positive macrophages. Moreover, most of CD68-positive macrophages expressed both CCR2 and CX3CR1. Morphometrically, the average of CCR2- and CX3CR1-positive macrophages was significantly increased in sepsis group, compared with control group (sepsis vs. control: 41.6+/-1.3% vs. 8.0+/-0.4% in CCR2; 36.2+/-1.3% vs. 9.2+/-0.4% in CX3CR1). These observations implied that CCR2- or CX3CR1-positive macrophages were recruited into the lungs under several pathological conditions. In particular, their recruitment might be more evident in sepsis. Moreover, from the forensic aspects, immunohistochemical detection of CCR2 and CX3CR1 expression in the lungs can be considered as valuable diagnostic tools for the postmortem diagnosis of sepsis.

  4. The role of endocrine mechanisms in ventilator-associated lung injury in critically ill patients.

    Science.gov (United States)

    Penesova, A; Galusova, A; Vigas, M; Vlcek, M; Imrich, R; Majek, M

    2012-07-01

    The critically ill subjects are represented by a heterogeneous group of patients suffering from a life-threatening event of different origin, e.g. trauma, cardiopulmonary failure, surgery or sepsis. The majority of these patients are dependent on the artificial lung ventilation, which means a life-saving chance for them. However, the artificial lung ventilation may trigger ventilation-associated lung injury (VALI). The mechanical ventilation at higher volumes (volutrauma) and pressure (barotrauma) can cause histological changes in the lungs including impairments in the gap and adherens junctions and desmosomes. The injured lung epithelium may lead to an impairment of the surfactant production and function, and this may not only contribute to the pathophysiology of VALI but also to acute respiratory distress syndrome. Other components of VALI are atelectrauma and toxic effects of the oxygen. Collectively, all these effects may result in a lung inflammation associated with a subsequent profibrotic changes, endothelial dysfunction, and activation of the local and systemic endocrine responses such as the renin-angiotensin system (RAS). The present review is aimed to describe some of the pathophysiologic aspects of VALI providing a basis for novel therapeutic strategies in the critically ill patients.

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

    Science.gov (United States)

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

    2007-09-01

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

  6. The role of alveolar epithelium in radiation-induced lung injury.

    Science.gov (United States)

    Almeida, Celine; Nagarajan, Devipriya; Tian, Jian; Leal, Sofia Walder; Wheeler, Kenneth; Munley, Michael; Blackstock, William; Zhao, Weiling

    2013-01-01

    Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy) and fractionated doses (24-36 Gy) of (137)Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c(+) cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.

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

    Institute of Scientific and Technical Information of China (English)

    Jian-Xin Zhang; Sheng-Chun Dang

    2006-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

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

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

    NARCIS (Netherlands)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    2012-10-15

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

  15. DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation.

    Science.gov (United States)

    Spahn, Jessica H; Li, Wenjun; Bribriesco, Alejandro C; Liu, Jie; Shen, Hua; Ibricevic, Aida; Pan, Jie-Hong; Zinselmeyer, Bernd H; Brody, Steven L; Goldstein, Daniel R; Krupnick, Alexander S; Gelman, Andrew E; Miller, Mark J; Kreisel, Daniel

    2015-04-15

    Neutrophils are critical mediators of innate immune responses and contribute to tissue injury. However, immune pathways that regulate neutrophil recruitment to injured tissues during noninfectious inflammation remain poorly understood. DAP12 is a cell membrane-associated protein that is expressed in myeloid cells and can either augment or dampen innate inflammatory responses during infections. To elucidate the role of DAP12 in pulmonary ischemia/reperfusion injury (IRI), we took advantage of a clinically relevant mouse model of transplant-mediated lung IRI. This technique allowed us to dissect the importance of DAP12 in tissue-resident cells and those that infiltrate injured tissue from the periphery during noninfectious inflammation. Macrophages in both mouse and human lungs that have been subjected to cold ischemic storage express DAP12. We found that donor, but not recipient, deficiency in DAP12 protected against pulmonary IRI. Analysis of the immune response showed that DAP12 promotes the survival of tissue-resident alveolar macrophages and contributes to local production of neutrophil chemoattractants. Intravital imaging demonstrated a transendothelial migration defect into DAP12-deficient lungs, which can be rescued by local administration of the neutrophil chemokine CXCL2. We have uncovered a previously unrecognized role for DAP12 expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking.

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

    Science.gov (United States)

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

    2016-04-01

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

  17. Effects of hypercapnia and hypercapnic acidosis on attenuation of ventilator-associated lung injury.

    Science.gov (United States)

    Ismaiel, N M; Henzler, D

    2011-07-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with impaired gas exchange, severe inflammation and alveolar damage including cell death. Patients with ALI or ARDS typically experience respiratory failure and thus require mechanical ventilation for support, which itself can aggravate lung injury. Recent developments in this field have revealed several therapeutic strategies that improve gas exchange, increase survival and minimize the deleterious effects of mechanical ventilation. Among those strategies is the reduction in tidal volume and allowing hypercapnia to develop during ventilation, or actively inducing hypercapnia. Here, we provide an overview of hypercapnia and the hypercapnic acidosis that typically follows, as well as the therapeutic effects of hypercapnia and acidosis in clinical studies and experimental models of ALI. Specifically, we review the effects of hypercapnia and acidosis on the attenuation of pulmonary inflammation, reduction of apoptosis in alveolar epithelial cells, improvement in sepsis-induced ALI and the therapeutic effects on other organ systems, as well as the potentially harmful effects of these strategies. The clinical implications of hypercapnia and hypercapnic acidosis are still not entirely clear. However, future research should focus on the intracellular signaling pathways that mediate ALI development, potentially focusing on the role of reactive biological species in ALI pathogenesis. Future research can also elucidate how such pathways may be targeted by hypercapnia and hypercapnic acidosis to attenuate lung injury.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  19. Influence of lung injury on cardiac output measurement using transpulmonary ultrasound dilution: a validation study in neonatal lambs

    NARCIS (Netherlands)

    Vrancken, S.L.A.G.; Boode, W.P. de; Hopman, J.C.W.; Looijen-Salamon, M.G.; Liem, K.D.; Heijst, A.F. van

    2012-01-01

    BACKGROUND: /st> Transpulmonary ultrasound dilution (TPUD) is a promising method for cardiac output (CO) measurement in severely ill neonates. The incidence of lung injury in this population is high, which might influence CO measurement using TPUD because of altered lung perfusion. We evaluated t

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-08-15

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

  2. Intensive insulin treatment attenuates burn-initiated acute lung injury in rats: role of the protective endothelium.

    Science.gov (United States)

    Zhang, Wan-Fu; Zhu, Xiong-Xiang; Hu, Da-Hai; Xu, Cheng-Feng; Wang, Yun-Chuan; Lv, Gen-Fa

    2011-01-01

    Nonmetabolic effects of intensive insulin therapy in critically ill patients have been reported, but the underlying mechanisms are unclear. This study was designed to test the hypothesis that intensive insulin treatment would attenuate burn-induced acute lung injury by protecting the pulmonary microvascular endothelium. The rat model of burn injury was achieved by exposure to 92°C water for 18 seconds. The rats were randomly allocated into the sham, burn/normal saline (NS), and burn/intensive insulin treatment groups. Blood glucose level was maintained between 5 and 7 mmol/L in rats in the burn/intensive insulin treatment group. Pulmonary injury was assessed by hematoxylin and eosin staining, scanning electron microscopy, bronchoalveolar lavage fluid protein concentrations, the lung wet:dry weight ratio, and lung myeloperoxidase activity. Pulmonary microvascular endothelial cells were examined by transmission electron microscopy. Western blotting was used to determine the protein expression of caspase-3. Intensive insulin treatment markedly attenuated the acute lung injury, revealed by improvements in histological features and significant decreases in bronchoalveolar lavage fluid protein concentrations, pulmonary wet:dry weight ratio, and myeloperoxidase activity at 12 hours after injury (P insulin treatment group when compared with the burn/NS group. Overall, intensive insulin treatment efficiently attenuated pulmonary microvascular endothelial cell dysfunction, decreased cell apoptosis, and inhibited acute lung injury after a burn. These findings may be useful in preventing organ failure after burn injury.

  3. Late infusion of cloned marrow fibroblasts stimulates endogenous recovery from radiation-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Mineo Iwata

    Full Text Available In the current study, we used a canine model of radiation-induced lung injury to test the effect of a single i.v. infusion of 10×10(6/kg of marrow fibroblasts on the progression of damage following 15 Gy exposure to the right lung. The fibroblasts, designated DS1 cells, are a cloned population of immortalized cells isolated from a primary culture of marrow stromal cells. DS1 cells were infused at week 5 post-irradiation when lung damage was evident by imaging with high-resolution computed tomography (CT. At 13 weeks post-irradiation we found that 4 out of 5 dogs receiving DS1 cells had significantly improved pulmonary function compared to 0 out of 5 control dogs (p = 0.047, Fisher's Exact. Pulmonary function was measured as the single breath diffusion capacity-hematocrit (DLCO-Hct, the total inspiratory capacity (IC, and the total lung capacity (TLC, which differed significantly between control and DS1-treated dogs; p = 0.002, p = 0.005, and p = 0.004, respectively. The DS1-treated dogs also had less pneumonitis detected by CT imaging and an increased number of TTF-1 (thyroid transcription factor 1, NKX2-1 positive cells in the bronchioli and alveoli compared to control dogs. Endothelial-like progenitor cells (ELC of host origin, detected by colony assays, were found in peripheral blood after DS1 cell infusion. ELC numbers peaked one day after infusion, and were not detectable by 7 days. These data suggest that infusion of marrow fibroblasts stimulates mobilization of ELC, which is associated with a reduction in otherwise progressive radiation-induced lung injury. We hypothesize that these two observations are related, specifically that circulating ELC contribute to increased angiogenesis, which facilitates endogenous lung repair.

  4. Osteopontin protects against hyperoxia-induced lung injury by inhibiting nitric oxide synthases

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiang-feng; LIU Shuang; ZHOU Yu-jie; ZHU Guang-fa; Hussein. D Foda

    2010-01-01

    Background Exposure of adult mice to more than 95% O_2 produces a lethal injury by 72 hours. Nitric oxide synthase (NOS) is thought to contribute to the pathophysiology of murine hyperoxia-induced acute lung injury (ALI). Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. OPN inhibits inducible nitric oxide synthase (iNOS), which generates large amounts of nitric oxide production. However, the relationship between nitric oxide and endogenous OPN in lung tissue during hyperoxia-induced ALI has not yet been elucidated, thus we examined the role that OPN plays in the hyperoxia-induced lung injury and its relationships with NOS.Methods One hundred and forty-four osteopontin knock-out (KO) mice and their matched wild type background control (WT) were exposed in sealed cages >95% oxygen or room air for 24-72 hours, and the severity of lung injury was assessed; expression of OPN, endothelial nitric oxide synthase (eNOS) and iNOS mRNA in lung tissues at 24,48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR); immunohistochemistry (IHC) was performed for the detection of iNOS, eNOS, and OPN protein in lung tissues.Results OPN KO mice developed more severe acute lung injury at 72 hours of hyperoxia. The wet/dry weight ratio increased to 6.85±0.66 in the KO mice at 72 hours of hyperoxia as compared to 5.31±0.92 in the WT group (P<0.05). iNOS mRNA (48 hours: 1.04±0.08 vs. 0.63±0.09, P<0.01; 72 hours: 0.89±0.08 vs. 0.72±0.09, P<0.05) and eNOS mRNA (48 hours: 0.62±0.08 vs. 0.43±0.09, P<0.05; 72 hours: 0.67±0.08 vs. 0.45±0.09, P<0.05) expression was more significantly increased in OPN KO mice than their matched WT mice when exposed to hyperoxia. IHC study showed higher expression of iNOS (20.54±3.18 vs. 12.52±2.46, P <0.05) and eNOS (19.83±5.64 vs. 9.45±3.82, P <0.05) in lung tissues of OPN KO mice at 72 hours of hyperoxia. Conclusion OPN can protect against hyperoxia-induced lung

  5. ω-3多不饱和脂肪酸对内毒素致大鼠急性肺损伤的影响%Effect of omega-3 polyunsaturated fatty acid on lipopolysaccharide-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    赵艳; 柳欣欣; 郭丹; 王磊; 陈平

    2013-01-01

    Objective To evaluate the effect of dietary ω-3 polyunsaturated fatty acid (PUFA) supplementation on lipopolysaccharide (LPS)-induced acute lung injury in rats.Methods Totally 58 male SD rats were divided into control group (n =10),model group (n =12),ω-3 PUFA high-dose group (n =12),ω-3PUFA medium-dose group (n =12),and ω-3 PUFA low-dose group (n =12).Seven days before model establishment,rats in the three ω-3 PUFA groups were orally given ω-3 PUFA at 1,0.5,and 0.25 g/kg body weight once per day,respectively,for seven consecutive days.Twenty-four hours after the last administration,all rats except those in the control group were given intravenous injection of LPS (6 mg/kg) at caudal vein to establish the model of acute lung injury.Body temperature was measured at 0,6,and 24 hour.Blood samples were collected from the eye venous plexus for routine blood tests and blood biochemical tests 24 hours after modeling.After the rats were sacrificed,the left lung was harvested for measuring the wet weight and dry weight and calculating the wet/dry weight ratio (W/D).The right lung was harvested for pathological observation under light microscope and calculation of semi-quantitative pathological index (PI).Results Twenty-four hours after modeling,deaths were noted in all groups except the control group.After injection of LPS,rats curled with little movements.At 6 hour,the body temperature was significantly higher in the model group than in the control group [(37.4 ±0.27)℃ vs.(35.9 ±0.05) ℃,P =0.00] ; it was (36.2 ±0.38)℃,(36.3 ±0.30)℃,and (36.3 ± 0.32) ℃ in the ω-3 PUFA high-,medium-,and low-dose groups,which were significantly lower than that in the model group (all P =0.01).The amounts of white blood cells,neutrophils,and lymphocytes increased in the model group,but showing no significant difference compared with the other groups.The serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels were significantly higher in

  6. Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Warner, R L

    1997-01-01

    The C-X-C chemokines of the IL-8 family possess potent chemotactic activity for neutrophils, but their in vivo role in inflammatory responses is not well understood. In the IgG immune complex-induced model of acute lung inflammatory injury in the rat we have evaluated the roles of two rat...... chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences...... by 125I-labeled albumin leakage from the pulmonary vasculature) and reduced neutrophil accumulation in the lung (as determined by myeloperoxidase (MPO content) and neutrophil counts in bronchoalveolar lavage (BAL) fluids); however, no change in TNF-alpha levels in BAL fluids was found. Chemotactic...

  7. Respiratory compliance but not gas exchange correlates with changes in lung aeration after a recruitment maneuver: an experimental study in pigs with saline lavage lung injury

    Science.gov (United States)

    Henzler, Dietrich; Pelosi, Paolo; Dembinski, Rolf; Ullmann, Annette; Mahnken, Andreas H; Rossaint, Rolf; Kuhlen, Ralf

    2005-01-01

    Introduction Atelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchange Methods In eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH2O for 40 s with a constant positive end-expiratory pressure of 10 cmH2O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung. Results Nonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve

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

    Institute of Scientific and Technical Information of China (English)

    Hong-Mei Liu; Yu-Na Guo

    2014-01-01

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

  9. A Histological Assessment of Lung Injury in Rats Exposed to Inhaled Sulfur Mustard across Dose and Time

    Science.gov (United States)

    2015-06-01

    following HD exposure at 7.5 hours (3.0 mg/kg). Histopathology of the BALT and overlying respiratory epithelium in the accessory lung lobe. Note the...USAMRICD‐TR‐15‐02  A Histological Assessment of  Lung  Injury in Rats  Exposed to Inhaled Sulfur Mustard across Dose  and Time    Derron A... Lung Injury in rats Exposed to Inhaled Sulfur Mustard across Dose and Time 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  10. Tracking of Mesenchymal Stem Cells with Fluorescence Endomicroscopy Imaging in Radiotherapy-Induced Lung Injury

    Science.gov (United States)

    Perez, Jessica R.; Ybarra, Norma; Chagnon, Frederic; Serban, Monica; Lee, Sangkyu; Seuntjens, Jan; Lesur, Olivier; El Naqa, Issam

    2017-01-01

    Mesenchymal stem cells (MSCs) have potential for reducing inflammation and promoting organ repair. However, limitations in available techniques to track them and assess this potential for lung repair have hindered their applicability. In this work, we proposed, implemented and evaluated the use of fluorescence endomicroscopy as a novel imaging tool to track MSCs in vivo. MSCs were fluorescently labeled and injected into a rat model of radiation-induced lung injury via endotracheal (ET) or intravascular (IV) administration. Our results show that MSCs were visible in the lungs with fluorescence endomicroscopy. Moreover, we developed an automatic cell counting algorithm to quantify the number of detected cells in each condition. We observed a significantly higher number of detected cells in ET injection compared to IV and a slight increase in the mean number of detected cells in irradiated lungs compared to control, although the latter did not reach statistical significance. Fluorescence endomicroscopy imaging is a powerful new minimally invasive and translatable tool that can be used to track and quantify MSCs in the lungs and help assess their potential in organ repair. PMID:28102237

  11. Tracking of Mesenchymal Stem Cells with Fluorescence Endomicroscopy Imaging in Radiotherapy-Induced Lung Injury

    Science.gov (United States)

    Perez, Jessica R.; Ybarra, Norma; Chagnon, Frederic; Serban, Monica; Lee, Sangkyu; Seuntjens, Jan; Lesur, Olivier; El Naqa, Issam

    2017-01-01

    Mesenchymal stem cells (MSCs) have potential for reducing inflammation and promoting organ repair. However, limitations in available techniques to track them and assess this potential for lung repair have hindered their applicability. In this work, we proposed, implemented and evaluated the use of fluorescence endomicroscopy as a novel imaging tool to track MSCs in vivo. MSCs were fluorescently labeled and injected into a rat model of radiation-induced lung injury via endotracheal (ET) or intravascular (IV) administration. Our results show that MSCs were visible in the lungs with fluorescence endomicroscopy. Moreover, we developed an automatic cell counting algorithm to quantify the number of detected cells in each condition. We observed a significantly higher number of detected cells in ET injection compared to IV and a slight increase in the mean number of detected cells in irradiated lungs compared to control, although the latter did not reach statistical significance. Fluorescence endomicroscopy imaging is a powerful new minimally invasive and translatable tool that can be used to track and quantify MSCs in the lungs and help assess their potential in organ repair.

  12. Mitigating Role of Quercetin Against Cyclophosphamide-Induced Lung Injury in Rats

    Directory of Open Access Journals (Sweden)

    Nora A. Asry

    2014-05-01

    Full Text Available Quercetin (Qur, a polyphenolic flavonoid compound present in large amounts in vegetables and fruits, plays important roles in human health through its antioxidant activity. This study was conducted to investigate the possible modulatory effect of Qur against cyclophosphamide (CP-induced lung oxidative damage and to highlight the underlying mechanisms of such effect. Male Sprague-Dawely rats were divided into four groups. Group I was control. Group II received Qur (100 mg/kg/d. p.o. for 14 consecutive days. Group III was injected once with CP (150 mg/kg, i.p.. Group IV received Qur for 7 consecutive days, before and after CP injection.A single i.p. injection of CP markedly increased the level of serum biomarkers; total protein, LDH. Cyclophosphamide significantly increased the lung content of lipid peroxides and decreased levels of reduced glutathione. Treatment of rats with Qur for 7 days prior to and 7 days after cyclophosphamide significantly ameliorated the alterations in lung and serum biomarkers associated with inflammatory reactions. Moreover, Qur attenuated the secretion of pro-inflammatory cytokine, TNF-α in rat serum. In addition, Qur slightly ameliorated CP-induced histopathological changes in lung tissue. Our results suggest that Qur produces a protective effect against CP-induced lung injury and suggest a role of oxidative stress and inflammation in the pathogenesis.

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

    Science.gov (United States)

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

    2001-12-01

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

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

    Directory of Open Access Journals (Sweden)

    M.F.R. Silva

    1998-03-01

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

  15. Activation of Akt protects alveoli from neonatal oxygen-induced lung injury.

    Science.gov (United States)

    Alphonse, Rajesh S; Vadivel, Arul; Coltan, Lavinia; Eaton, Farah; Barr, Amy J; Dyck, Jason R B; Thébaud, Bernard

    2011-02-01

    Bronchopulmonary dysplasia (BPD) is the main complication of extreme prematurity, resulting in part from mechanical ventilation and oxygen therapy. Currently, no specific treatment exists for BPD. BPD is characterized by an arrest in alveolar development and increased apoptosis of alveolar epithelial cells (AECs). Type 2 AECs are putative distal lung progenitor cells, capable of regenerating alveolar homeostasis after injury. We hypothesized that the protection of AEC2 death via the activation of the prosurvival Akt pathway prevents arrested alveolar development in experimental BPD. We show that the pharmacologic inhibition of the prosurvival factor Akt pathway with wortmannin during the critical period of alveolar development impairs alveolar development in newborn rats, resulting in larger and fewer alveoli, reminiscent of BPD. Conversely, in an experimental model of BPD induced by oxygen exposure of newborn rats, alveolar simplification is associated with a decreased activation of lung Akt. In vitro studies with rat lung epithelial (RLE) cells cultured in hyperoxia (95% O(2)) showed decreased apoptosis and improved cell survival after the forced expression of active Akt by adenovirus-mediated gene transfer. In vivo, adenovirus-mediated Akt gene transfer preserves alveolar architecture in the newborn rat model of hyperoxia-induced BPD. We conclude that inhibition of the prosurvival factor Akt disrupts normal lung development, whereas the expression of active Akt in experimental BPD preserves alveolar development. We speculate that the modulation of apoptosis may have therapeutic potential in lung diseases characterized by alveolar damage.

  16. Triptolide inhibits NF-κB activation and reduces injury of donor lung induced by ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Jing-kang HE; Shu-dong YU; Hong-Jun ZHU; Jun-chao WU; Zhen-ghong QIN

    2007-01-01

    Aim: To investigate the protective effect of triptolide (TRI) on ischemia/reperfusion- induced injury of transplanted rabbit lungs and to investigate the mechanisms underlying the actions of TRI. Methods: We established the rabbit lung trans- plantation model and studied lung injury induced by ischemia/reperfusion and the inhibitory effect of TRI on NF-r,B. The severity of lung injury was determined by a gradual decline in PvO2, the degree of lung edema, the increase in the myeloperoxidase (MPO) activity, and the ultrastructural changes of transplanted lungs. The activation of NF-r,B was measured by immunohistochemistry. The increase in intercellular adhesion molecule- 1 (ICAM- 1), which is the target gene of NF-κB, was evaluated by ELISA. Results: After reperfusion, there was a gradual decline in the PvO2 level in the control group (group I). The level of PvO2 in the group treated with lipopolysaccharide (group Ⅱ) was significantly decreased, whereas that of the group treated with TRI (group Ⅲ) was markedly improved (P<0.01). In group Ⅲ, the activity of MPO was downregulated, and the pulmonary edema did not become severe and the ultrastructure of the donor lung remained normal. The activity of NF-κB and the expression of ICAM-1 was significantly increased in the donor lungs. TRI blocked NF-κB activation and ICAM-1 expression. Conclusion: The effects of TRI on reducing injury to donor lungs induced by ischemia/reperfusion may possibly be mediated by inhibiting the activity of NF-κB and the expression of the NF-rd3 target gene ICAM-1. Thus, TRI could be used in lung transplantations for improving the function of donor lungs.

  17. Regulation on the expression of Clara cell secretory protein in the lungs of the rats with acute lung injury by growth hormone

    Institute of Scientific and Technical Information of China (English)

    MIN Jia; LUO Fo-quan; ZHAO Wei-lu

    2012-01-01

    Background Clara cell secretory protein (CC16) is an important lung derived protective factor and may play an important role on the pathogenesis of acute lung injury (ALl) induced by endotoxemia.Growth hormone (GH) is an important anabolism hormone secreted by GH cells of the hypophysis.Pravious research showed that GH would significantly exacerbate ALl induced by endotoxemia,but the mechanism is not very clear yet.Whether the effects are related to CC16 or not is undetermined.Methods One hundred and twelve male Sprague-Dawley rats were randomly divided into an ALl group and a GH group.The rats in the two groups were subdivided into seven subgroups,according to injection with lipopolysaccharides (LPS) or not,then according to different intervals of time after LPS injection; 0 hour (pre-injection of LPS,acted as control group),0.5 hour,1 hour,2 hours,4 hours,6 hours and 24 hours for subgroups.Pulmonary alveolar septa area density (PASAD) and ploymorphonuclear cells (PMN) in the lungs were analyzed morphometrically.The levels of tumor necrosis factor (TNF) and interleukin 6 (1L-6) were determined by radioimmunoassay.To analyze the expression and activation of nuclear factor kappa B (NF-kB),the numbers of NF-kB positive cells in lungs were counted after immunofluorescence staining.and the levels of NF-KB inhibitory protein-α (1KB-α) in lung homogenates of rats were detected by Western blotting.The expression levels of CC16 mRNA in lungs of the rats with ALl were determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).The levels of CC16 protein in lung homogenates were detected by Western blotting.Results Half an hour after LPS injury both the PASAD and PMN numbers in lungs of the rats with ALl began to increase significantly and peaked at 6-hour post-injury.They then began to recover and reached normal levels at 24-hour post-injury.Both the PASAD and PMN numbers in the GH group increased more significantly than those in the ALl group

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

    Directory of Open Access Journals (Sweden)

    JM Real

    2008-06-01

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

  19. Study on Effect and Mechanism of Sodium Ferulate in Preventing and Treating Ozone Induced Lung Injury in Mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To study the effect and mechanism of sodium ferulate (SF) in preventing and treating ozone (O3) induced lung oxidative injury in mice. Methods: Lung oxidative injury model mice were established by making them inhale O3. The activity of anti-oxidase and membranous microviscosity in epithelial cells in the lung of mice were determined, and the ultrastructural change of lung tissues was observed with electromicroscopy. Results: Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were reduced, while membranous lipo-microviscosity significantly increased in the pulmonary epithelial cells of model mice, revealing ultrastructural change. These abnormal changes were reversed by SF treatment, which was manifested as the significantly raised activities of SOD and GSH-Px after treatment with high and moderate doses of SF, showing a significant difference compared with those in the model group (P<0.01). Membranous lipo-microviscosity basically approached that in the control group (P>0.05); electron microscopic examination showed a basically normal morphological structure of pulmonary epithelial cells, with the change in lung injury significantly milder than that in the model group. Conclusion: O3 could induce oxidative injury of lungs in mice, and SF could enhance the anti-oxidation capacity of mice and scavenge the oxygen free radicals so as to alleviate the injury.

  20. The Role of Nitric Oxide in Hyperoxic Lung Injury in Premature Rats

    Institute of Scientific and Technical Information of China (English)

    常立文; 马丽亚; 张晓慧; 陈晔

    2001-01-01

    To investigate the role of nitric oxide (NO) in hyperoxic lung injury, the 3-day-old preterm rats were randomly assigned to four groups: group I (hyperoxia group), group Ⅱ (hyperoxia+Nw-nitro-L-arginine methyl ester (L-NAME) group), group Ⅲ (air group), and group Ⅳ (air+L-NAME) group. Group Ⅰ and Ⅱ were exposed to ≥90 % O2 for 3 or 7 days. Group Ⅱ and Ⅳ received subcutaneous L-NAMEy on daily basis (20 mg/kg). After 3 day or 7 day exposure, the lung wet weight/dry weight ratio (W/D), total protein and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lung pathology were examined in all groups. NO content, expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in lungs were measured in group Ⅰ and Ⅲ. Our results showed that after 3 day exposure, group Ⅰ appeared acute lung injury characterized by the increase of MDA content (P<0.01) and the presence of hyperaemia, red cell extravasation and inflammatory infiltration; after 7 day exposure, except MDA, total protein and W/D were also increased in comparison with group Ⅲ (P<0.01, 0.05), pathological changes were more severe than those after 3 day exposure. After 3 and 7 day exposure, total protein in group Ⅱ was significantly increased as compared with group Ⅰ (P<0.01 for both). The pulmonary acute inflammatory changes were more obvious in group Ⅱ than in group Ⅰ. Occasionally, mild hemorrhage was detected in the lungs of group Ⅳ. BALF protein content in group IV was higher than that in group Ⅲ after 7 day exposure (P<0.01). After 3 and 7 day exposure, NO content in BALF were all significantly elevated in group Ⅰ as compared with group Ⅲ (P<0.01 for all). In the lungs of group Ⅰ, strong immunostaining for iNOS was observed in airway and alveolar epithelia, inflammatory cells, which were stronger than those in group Ⅲ. Expression of iNOS in rats after 7 day hyperoxic exposure was stronger than that after 3 day exposure. Shortly after 7 day exposure

  1. Loss of the intestinal mucus layer in the normal rat causes gut injury but not toxic mesenteric lymph nor lung injury.

    Science.gov (United States)

    Sharpe, Susan M; Qin, Xiaofa; Lu, Qi; Feketeova, Eleonora; Palange, David C; Dong, Wei; Sheth, Sharvil U; Lee, Marlon A; Reino, Diego; Xu, Da-Zhong; Deitch, Edwin A

    2010-11-01

    There is substantial evidence that gut barrier failure is associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors and mechanisms involved in gut injury are unknown. Our primary hypothesis is that loss of the intestinal mucus layer will result in injury of the normal gut that is exacerbated by the presence of luminal pancreatic proteases. Our secondary hypothesis is that the injury produced in the gut will result in the production of biologically active mesenteric lymph and consequently distant organ (i.e., lung) injury. To test this hypothesis, five groups of rats were studied: 1) uninstrumented naive rats; 2) control rats in which a ligated segment of distal ileum was filled with saline; 3) rats with pancreatic proteases placed in their distal ileal segments; 4) rats with the mucolytic N-acetylcysteine (NAC) placed in their distal ileal segments; and 5) rats exposed to NAC and pancreatic proteases in their ileal segments. The potential systemic consequences of gut injury induced by NAC and proteases were assessed by measuring the biological activity of mesenteric lymph as well as gut-induced lung injury. Exposure of the normal intestine to NAC, but not saline or proteases, led to increased gut permeability, loss of mucus hydrophobicity, a decrease in the mucus layer, as well as morphological evidence of villous injury. Although proteases themselves did not cause gut injury, the combination of pancreatic proteases with NAC caused more severe injury than NAC alone, suggesting that once the mucus barrier is impaired, luminal proteases can injure the now vulnerable gut. Because comparable levels of gut injury caused by systemic insults are associated with gut-induced lung injury, which is mediated by biologically active factors in mesenteric lymph, we next tested whether this local model of gut injury would produce active mesenteric lymph or lead to lung injury. It did not, suggesting that gut injury by itself may not

  2. Lung injury caused by greenstick fracture of the scapular body in a 6-year-old boy.

    Science.gov (United States)

    Shin, Sung Jin; Wang, Sung Il; Kim, Jung Ryul

    2016-04-01

    Complications caused by a scapular body fracture are rare, and usually occur due to concomitant injuries or nonunion. Intrathoracic displacement of a fractured scapula has only been described in two reports involving adolescents. In this report, we describe a 6-year-old boy with a parenchymal lung injury caused by a greenstick fracture fragment of the scapular body after being struck by a dump truck. Three-dimensional CT (3D CT) scan showed an incomplete fractured fragment impaling the left lung parenchyma resulting in pneumothorax, parenchymal contusion, and pneumatocele in the left upper lobe. The patient underwent emergency open reduction of the scapular fracture and chest tube insertion. A rare subtype of scapular fracture with resultant fragment rotation and intrathoracic penetration can injure the lung parenchyma. To the best of our knowledge, lung injury caused by incomplete fracture of the scapula in patients younger than 10 years has not been reported previously.

  3. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury.

    Science.gov (United States)

    Vaughan, Andrew E; Brumwell, Alexis N; Xi, Ying; Gotts, Jeffrey E; Brownfield, Doug G; Treutlein, Barbara; Tan, Kevin; Tan, Victor; Liu, Feng Chun; Looney, Mark R; Matthay, Michael A; Rock, Jason R; Chapman, Harold A

    2015-01-29

    Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ- and injury-specific. Current models in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers. By contrast, here we define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEP) cells present within normal distal lung. Quiescent LNEPs activate a ΔNp63 (a p63 splice variant) and cytokeratin 5 remodelling program after influenza or bleomycin injury in mice. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, at which point they differentiate towards mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single-cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signalling to activate the ΔNp63 and cytokeratin 5 program, and subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signalling after injury led to parenchymal 'micro-honeycombing' (alveolar cysts), indicative of failed regeneration. Lungs from patients with fibrosis show analogous honeycomb cysts with evidence of hyperactive Notch signalling. Our findings indicate that distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of the injury, and the outcomes of regeneration or fibrosis may depend in part on the dynamics of LNEP Notch signalling.

  4. 17β-Estradiol administration attenuates seawater aspiration-induced acute lung injury in rats.

    Science.gov (United States)

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

    2011-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

  7. Roles for C-X-C chemokines and C5a in lung injury after hindlimb ischemia-reperfusion

    DEFF Research Database (Denmark)

    Bless, N M; Warner, R L; Padgaonkar, V A;

    1999-01-01

    We evaluated the roles of the C-X-C chemokines cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) as well as the complement activation product C5a in development of lung injury after hindlimb ischemia-reperfusion in rats. During reperfusion, CD11b...... and CD18, but not CD11a, were upregulated on neutrophils [bronchoalveolar lavage (BAL) and blood] and lung macrophages. BAL levels of CINC and MIP-2 were increased during the ischemic and reperfusion periods. Treatment with either anti-CINC or anti-MIP-2 IgG significantly reduced lung vascular......, 58, and 23%, respectively (P MIP-2 as well as the complement activation product C5a are required for lung neutrophil recruitment and full induction of lung injury after hindlimb ischemia-reperfusion in rats....

  8. Fatal Hyperammonemic Brain Injury from Valproic Acid Exposure

    Directory of Open Access Journals (Sweden)

    Danny Bega

    2012-12-01

    Full Text Available Background: Hyperammonemia is known to cause neuronal injury, and can result from valproic acid exposure. Prompt reduction of elevated ammonia levels may prevent permanent neurological injury. We report a case of fatal hyperammonemic brain injury in a woman exposed to valproic acid. Case: A 38-year-old woman with schizoaffective disorder and recent increase in valproic acid dosage presented with somnolence and confusion and rapidly progressed to obtundation. Brain MRI showed diffuse bilateral restricted diffusion in nearly the entire cerebral cortex. She had normal liver function tests but serum ammonia level was severely elevated at 288 µmol/l. Genetic testing showed no mutation in urea cycle enzymes. Despite successful elimination of ammonia with hemodialysis she developed fatal cerebral edema. Conclusion: Cerebral edema secondary to hyperammonemia is potentially reversible if recognized early. Ammonia excretion can be facilitated by initiation of hemodialysis and administration of scavenging agents (sodium phenylacetate and sodium benzoate. Severe hyperammonemia can result from valproic acid exposure even in the absence of hepatotoxicity or inborn errors of metabolism. It is important to check serum ammonia in any patient with encephalopathy who has had recent valproic acid exposure.

  9. Effect of intermittent ventilation pretreatment on one-lung ventilation-induced lung injury in radical operation for lung cancer as well as HIF-1α/HO-1 expression

    Institute of Scientific and Technical Information of China (English)

    Wen-Xiong Liu; Min Gao; Xiao-Hong Pang

    2016-01-01

    Objective:To study the effect of intermittent ventilation pretreatment on one-lung ventilation-induced lung injury in radical operation for lung cancer as well as HIF-1α/ HO-1 expression. Methods: A total of 60 patients undergoing selective radical operation for lung cancer in our hospital from March 2011 to December 2015 were selected and divided into intermittent ventilation group and conventional ventilation group, intraoperative airway function and alveolar oxygenation function were analyzed, serum was collected to determine the levels of lung injury-related molecules, and non-ventilation-side lung tissue was collected to determine the levels of lung injury-related molecules and endoplasmic reticulum stress-related molecules as well as the expression levels of HIF-1α/HO-1.Results:Ppeak, Pplat, Raw and PaO2 at T0, T1 and T2 were not significantly different between two groups, Ppeak, Pplat and Raw of intermittent ventilation group at T3 were significantly lower than those of conventional ventilation group and PaO2 was significantly higher than that of conventional ventilation group; KL-6, sRAGE and SP-A levels in serum as well as MPO, XOD, GRP78, CHOP, XBP1, ATF4, ATF6, PERK, HIF-1α and HO-1 levels in lung tissue of intermittent ventilation group were significantly lower than those of control group.Conclusion:Intermittent ventilation pretreatment can reduce one-lung ventilation-induced lung injury in radical operation for lung cancer, improve airway function and alveolar oxygenation function, and inhibit endoplasmic reticulum stress and the expression of HIF-1α/HO-1.

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

    Science.gov (United States)

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

    2016-05-01

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

  11. Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice.

    Science.gov (United States)

    Tavares, Luciana P; Garcia, Cristiana C; Vago, Juliana P; Queiroz-Junior, Celso M; Galvão, Izabela; David, Bruna A; Rachid, Milene A; Silva, Patrícia M R; Russo, Remo C; Teixeira, Mauro M; Sousa, Lirlândia P

    2016-07-01

    Pneumococcal pneumonia is a leading cause of mortality worldwide. The inflammatory response to bacteria is necessary to control infection, but it may also contribute to tissue damage. Phosphodiesterase-4 inhibitors, such as rolipram (ROL), effectively reduce inflammation. Here, we examined the impact of ROL in a pneumococcal pneumonia murine model. Mice were infected intranasally with 10(5)-10(6) CFU of Streptococcus pneumoniae, treated with ROL in a prophylactic or therapeutic schedule in combination, or not, with the antibiotic ceftriaxone. Inflammation and bacteria counts were assessed, and ex vivo phagocytosis assays were performed. ROL treatment during S. pneumoniae infection decreased neutrophil recruitment into lungs and airways and reduced lung injury. Prophylactic ROL treatment also decreased cytokine levels in the airways. Although modulation of inflammation by ROL ameliorated pneumonia, bacteria burden was not reduced. On the other hand, antibiotic therapy reduced bacteria without reducing neutrophil infiltration, cytokine level, or lung injury. Combined ROL and ceftriaxone treatment decreased lethality rates and was more efficient in reducing inflammation, by increasing proresolving protein annexin A1 (AnxA1) expression, and bacterial burden by enhancing phagocytosis. Lack of AnxA1 increased inflammation and lethality induced by pneumococcal infection. These data show that immunomodulatory effects of phosphodiesterase-4 inhibitors are useful during severe pneumococcal pneumonia and suggest their potential benefit as adjunctive therapy during infectious diseases.

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

    Directory of Open Access Journals (Sweden)

    Torii Y

    2011-09-01

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

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

    Science.gov (United States)

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

    2017-03-11

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

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Effect of tramadol on lung injury induced by skeletal muscle ischemia-reperfusion: an experimental study

    Directory of Open Access Journals (Sweden)

    Mohammad Ashrafzadeh Takhtfooladi

    2013-06-01

    Full Text Available OBJECTIVE: To determine whether tramadol has a protective effect against lung injury induced by skeletal muscle ischemia-reperfusion. METHODS: Twenty Wistar male rats were allocated to one of two groups: ischemia-reperfusion (IR and ischemia-reperfusion + tramadol (IR+T. The animals were anesthetized with intramuscular injections of ketamine and xylazine (50 mg/kg and 10 mg/kg, respectively. All of the animals underwent 2-h ischemia by occlusion of the femoral artery and 24-h reperfusion. Prior to the occlusion of the femoral artery, 250 IU heparin were administered via the jugular vein in order to prevent clotting. The rats in the IR+T group were treated with tramadol (20 mg/kg i.v. immediately before reperfusion. After the reperfusion period, the animals were euthanized with pentobarbital (300 mg/kg i.p., the lungs were carefully removed, and specimens were properly prepared for histopathological and biochemical studies. RESULTS: Myeloperoxidase activity and nitric oxide levels were significantly higher in the IR group than in the IR+T group (p = 0.001 for both. Histological abnormalities, such as intra-alveolar edema, intra-alveolar hemorrhage, and neutrophil infiltration, were significantly more common in the IR group than in the IR+T group. CONCLUSIONS: On the basis of our histological and biochemical findings, we conclude that tramadol prevents lung tissue injury after skeletal muscle ischemia-reperfusion.

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

    Directory of Open Access Journals (Sweden)

    Kupatt Christian

    2004-09-01

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

  17. Omega-3 fatty acids: a novel resort against gastrointestinal injury.

    Science.gov (United States)

    Ianiro, G; Franceschi, F; Bibbò, S; Gasbarrini, A

    2014-10-01

    The integrity of gastric barrier derives from the balance between defending and damaging factors. In particular, prostaglandins play a relevant role in the maintenance of gastric homeostasis and prevention of peptic disease, at different levels. Omega-3 fatty acids, particularly eicosapentanoic acid, are the precursors of the third series of prostaglandins (with anti-inflammatory properties), also reducing the formation of the second series of prostaglandins (pro-inflammatory ones). Such a pathophysiological rationale brought to the experimental application, both in animal models and, more recently, in humans, of omega-3 fatty acids against gastrointestinal damage. Omega-3 fatty acids have shown interesting results in preventing different types of gastric damage in mouse models. A large retrospective case-control study on patients taking both anti-thrombotic therapy and eicosapentanoic acid showed (although only at unadjusted analysis) an inverse correlation between consumption of eicosapentanoic acid and gastrointestinal injury. Prospective, well-designed, comparative studies are warranted to clarify if omega-3 fatty acids may represent, or not, a novel resort against gastrointestinal injury.

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

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  1. Protective effect of hypercapnic acidosis in ischemia-reperfusion lung injury is attributable to upregulation of heme oxygenase-1.

    Science.gov (United States)

    Wu, Shu-Yu; Li, Min-Hui; Ko, Fu-Chang; Wu, Geng-Chin; Huang, Kun-Lun; Chu, Shi-Jye

    2013-01-01

    Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP), an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF)-κB-α, increased IκB kinase (IKK)-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was mediated in

  2. Protective effect of hypercapnic acidosis in ischemia-reperfusion lung injury is attributable to upregulation of heme oxygenase-1.

    Directory of Open Access Journals (Sweden)

    Shu-Yu Wu

    Full Text Available Hypercapnic acidosis (HCA has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1 is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP, an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF-κB-α, increased IκB kinase (IKK-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was

  3. Pulmonary surfactant protein A inhibits the lipid peroxidation stimulated by linoleic acid hydroperoxide of rat lung mitochondria and microsomes.

    Science.gov (United States)

    Terrasa, Ana M; Guajardo, Margarita H; de Armas Sanabria, Elizabeth; Catalá, Angel

    2005-07-15

    Reactive oxygen species play an important role in several acute lung injuries. The lung tissue contains polyunsaturated fatty acids (PUFAs) that are substrates of lipid peroxidation that may lead to loss of the functional integrity of the cell membranes. In this study, we compare the in vitro protective effect of pulmonary surfactant protein A (SP-A), purified from porcine surfactant, against ascorbate-Fe(2+) lipid peroxidation stimulated by linoleic acid hydroperoxide (LHP) of the mitochondria and microsomes isolated from rat lung; deprived organelles of ascorbate and LHP were utilized as control. The process was measured simultaneously by chemiluminescence as well as by PUFA degradation of the total lipids isolated from these organelles. The addition of LHP to rat lung mitochondria or microsomes produces a marked increase in light emission; the highest value of activation was produced in microsomes (total chemiluminescence: 20.015+/-1.735 x 10(5) cpm). The inhibition of lipid peroxidation (decrease of chemiluminescence) was observed with the addition of increasing amounts (2.5 to 5.0 microg) of SP-A in rat lung mitochondria and 2.5 to 7.5 microg of SP-A in rat lung microsomes. The inhibitory effect reaches the highest values in the mitochondria, thus, 5.0 microg of SP-A produces a 100% inhibition in this membranes whereas 7.5 microg of SP-A produces a 51.25+/-3.48% inhibition in microsomes. The major difference in the fatty acid composition of total lipids isolated from native and peroxidized membranes was found in the arachidonic acid content; this decreased from 9.68+/-1.60% in the native group to 5.72+/-1.64% in peroxidized mitochondria and from 7.39+/-1.14% to 3.21+/-0.77% in microsomes. These changes were less pronounced in SP-A treated membranes; as an example, in the presence of 5.0 microg of SP-A, we observed a total protection of 20:4 n-6 (9.41+/-3.29%) in mitochondria, whereas 7.5 microg of SP-A produced a 65% protection in microsomes (5

  4. Metformin attenuates hyperoxia-induced lung injury in neonatal rats by reducing the inflammatory response.

    Science.gov (United States)

    Chen, Xueyu; Walther, Frans J; Sengers, Rozemarijn M A; Laghmani, El Houari; Salam, Asma; Folkerts, Gert; Pera, Tonio; Wagenaar, Gerry T M

    2015-08-01

    Because therapeutic options are lacking for bronchopulmonary dysplasia (BPD), there is an urgent medical need to discover novel targets/drugs to treat this neonatal chronic lung disease. Metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, may be a novel therapeutic option for BPD by reducing pulmonary inflammation and fibrosis and improving vascularization. We investigated the therapeutic potential of daily treatment with 25 and 100 mg/kg metformin, injected subcutaneously in neonatal Wistar rats with severe experimental BPD, induced by continuous exposure to 100% oxygen for 10 days. Parameters investigated included survival, lung and heart histopathology, pulmonary fibrin and collagen deposition, vascular leakage, right ventricular hypertrophy, and differential mRNA expression in the lungs of key genes involved in BPD pathogenesis, including inflammation, coagulation, and alveolar development. After daily metformin treatment rat pups with experimental BPD had reduced mortality, alveolar septum thickness, lung inflammation, and fibrosis, demonstrated by a reduced influx of macrophages and neutrophils and hyperoxia-induced collagen III and fibrin deposition (25 mg/kg), as well as improved vascularization (100 mg/kg) compared with control treatment. However, metformin did not ameliorate alveolar enlargement, small arteriole wall thickening, vascular alveolar leakage, and right ventricular hypertrophy. In conclusion metformin prolongs survival and attenuates pulmonary injury by reducing pulmonary inflammation, coagulation, and fibrosis but does not affect alveolar development or prevent pulmonary arterial hypertension and right ventricular hypertrophy in neonatal rats with severe hyperoxia-induced experimental BPD.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Jochen Grommes

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Rajit K. Basu

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  11. Protectin D1 promotes resolution of inflammation in a murine model of lipopolysaccharide-induced acute lung injury via enhancing neutrophil apoptosis

    Institute of Scientific and Technical Information of China (English)

    Li Xingwang; Li Chunlai; Liang Wandong; Bi Yuntian; Chen Maohua; Dong Sheng

    2014-01-01

    Background Protectin D1 (PD1),derived from docosahexaenoic acid,has been shown to control and resolve inflammation in some experimental models of inflammatory disorders.We investigated the protective roles of protectin D1 in pulmonary inflammation and lung injury induced by lipopolysaccharide (LPS).Methods Mice were randomly assigned to six groups (n=6 per group):sham-vehicle group,sham-PD1 group,shamzVAD-fmk group,LPS-vehicle group,LPS-PD1 group,and LPS-PD1-zVAD-fmk group.Mice were injected intratracheally with 3 mg/kg LPS or saline,followed 24 hours later by intravenous injection of 200 μg/mouse PD1 or vehicle.At the same time,some mice were also injected intraperitoneally with the pan-caspase inhibitor zVAD-fmk.Seventy-two hours after LPS challenge,samples of pulmonary tissue and bronchoalveolar lavage fluid were collected.Optical microscopy was used to examine pathological changes in lungs.Cellularity and protein concentration in bronchoalveolar lavage fluid were analyzed.Lung wet/dry ratios and myeloperoxidase activity were measured.Apoptosis of neutrophils in bronchoalveolar lavage fluid (BALF) was also evaluated by flow cytometry.Results Intratracheal instillation of LPS increased neutrophil counts,protein concentration in bronchoalveolar lavage fluid and myeloperoxidase activity,it induced lung histological injury and edema,and also suppressed apoptosis of neutrophils in BALF.Posttreatment with PD1 inhibited LPS-evoked changes in BALF neutrophil counts and protein concentration and lung myeloperoxidase activity,with the outcome of decreased pulmonary edema and histological injury.In addition,PD1 promoted apoptosis of neutrophils in BALF.The beneficial effects of PD1 were blocked by zVAD-fmk.Conclusion Posttreatment with PD1 enhances resolution of lung inflammation during LPS-induced acute lung injury by enhancing apoptosis in emigrated neutrophils,which is,at least in part,caspase-dependent.

  12. Anti-transforming growth factor-beta monoclonal antibodies prevent lung injury in hemorrhaged mice.

    Science.gov (United States)

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

    1994-09-01

    Acute lung injury, characterized as the adult respiratory distress syndrome (ARDS), is a common clinical occurrence following blood loss and injury. We previously found increased levels of transforming growth factor (TGF)-beta 1 mRNA in murine intraparenchymal mononuclear cells and in alveolar macrophages within 1 h after hemorrhage. Because TGF-beta has potent proinflammatory and immunoregulatory properties, we investigated the effect of blocking TGF-beta with mAb on hemorrhage-induced pathology, cytokine mRNA levels in lungs, as well as survival from pneumonia. Mice treated with anti-TGF-beta mAb showed normal pulmonary histology 3 days after hemorrhage and resuscitation in contrast to the mononuclear and neutrophil infiltrates, intraalveolar hemorrhage, and interstitial edema found in hemorrhaged mice either treated with control antibody or not treated with any antibody. Decreased mRNA levels for IL-1 beta, TNF-alpha, IL-6, IL-10, and IFN-gamma as compared with untreated, hemorrhaged controls were present in intraparenchymal pulmonary mononuclear cells following therapy with anti-TGF-beta. In contrast, therapy with anti-TGF-beta increased mRNA levels for IL-1 beta and TNF-alpha in alveolar macrophages and for TGF-beta in peripheral blood mononuclear cells collected 3 days after hemorrhage. Administration of anti-TGF-beta to hemorrhaged mice did not correct the enhanced susceptibility to Pseudomonas aeruginosa pneumonia that exists after hemorrhage. These results suggest that TGF-beta has an important role in hemorrhage-induced acute lung injury, but does not contribute to the post-hemorrhage depression in pulmonary antibacterial response.

  13. Systematic review and meta-analysis of nasal potential difference in hypoxia-induced lung injury.

    Science.gov (United States)

    Su, Zhenlei; Zhu, Lili; Wu, Jing; Zhao, Runzhen; Ji, Hong-Long

    2016-08-04

    Nasal potential difference (NPD), a well-established in vivo clinical test for cystic fibrosis, reflects transepithelial cation and anion transport in the respiratory epithelium. To analyze whether NPD can be applied to diagnose hypoxic lung injury, we searched PubMed, EMBASE, Scopus, Web of Science, Ovid MEDLINE, and Google Scholar, and analyzed data retrieved from eleven unbiased studies for high altitude pulmonary edema (HAPE) and respiratory distress syndrome (RDS) using the software RevMan and R. There was a significant reduction in overall basal (WMD -5.27 mV, 95% CI: -6.03 to -4.52, P < 0.00001, I(2) = 42%), amiloride-sensitive (ENaC) (-2.87 mV, 95% CI: -4.02 to -1.72, P < 0.00001, I(2) = 51%), and -resistant fractions (-3.91 mV, 95% CI: -7.64 to -0.18, P = 0.04, I(2) = 95%) in lung injury patients. Further analysis of HAPE and RDS separately corroborated these observations. Moreover, SpO2 correlated with ENaC-associated NPD positively in patients only, but apparently related to CFTR-contributed NPD level inversely. These correlations were confirmed by the opposite associations between NPD values and altitude, which had a negative regression with SpO2 level. Basal NPD was significantly associated with amiloride-resistant but not ENaC fraction. Our analyses demonstrate that acute lung injury associated with systemic hypoxia is characterized by dysfunctional NPD.

  14. Erdosteine ameliorates lung injury induced by transient aortic occlusion in rats

    OpenAIRE

    Kurtoglu, Tunay; Sacar,Mustafa; Inan, Bilal Kaan; Duver, M Harun; Guler, Adem; Ucak, Alper; Us, Melih Hulusi; Yilmaz, Ahmet Turan

    2007-01-01

    Summary The aim of this experimental study was to evaluate the protective effect of erdosteine on lung injury induced by ischaemia−reperfusion (IR) of the lower extremities of rats. Wistar albino rats (n = 21) were divided into three groups. In the IR group (n = 7), the aorta was cross-clamped for two hours, followed by one hour of reperfusion. In the erdosteine group (n = 7), animals were pretreated with erdosteine 100 mg/kg daily via gastric lavage, starting three days before aortic occlusi...

  15. Multidetector computed tomography-spectrum of blunt chest wall and lung injuries in polytraumatized patients

    Energy Technology Data Exchange (ETDEWEB)

    Peters, S., E-mail: soeren.peters@rub.d [Department of Radiology and Nuclear Medicine, BG Universitaetsklinikum Bergmannsheil, Buerkle-de-la-Camp-Platz 1, 44789 Bochum (Germany); Nicolas, V.; Heyer, C.M. [Department of Radiology and Nuclear Medicine, BG Universitaetsklinikum Bergmannsheil, Buerkle-de-la-Camp-Platz 1, 44789 Bochum (Germany)

    2010-04-15

    Accidental injuries are the leading cause of death in the 15 to 44-year-old age group. Blunt chest trauma is often encountered in these patients and is associated with a mortality of up to 25%. Although conventional radiography still plays an important role in the initial emergency room setting, for follow-up in the intensive care unit, multidetector computed tomography has established itself as the standard imaging method for the evaluation of chest trauma patients. The following review presents salient radiological findings of the chest wall and shoulder girdle, thoracic spine, pleural space, and lung in polytraumatized patients.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  17. Heme oxygenase-1, a critical arbitrator of cell death pathways in lung injury and disease.

    Science.gov (United States)

    Morse, Danielle; Lin, Ling; Choi, Augustine M K; Ryter, Stefan W

    2009-07-01

    Increases in cell death by programmed (i.e., apoptosis, autophagy) or nonprogrammed mechanisms (i.e., necrosis) occur during tissue injury and may contribute to the etiology of several pulmonary or vascular disease states. The low-molecular-weight stress protein heme oxygenase-1 (HO-1) confers cytoprotection against cell death in various models of lung and vascular injury by inhibiting apoptosis, inflammation, and cell proliferation. HO-1 serves a vital metabolic function as the rate-limiting step in the heme degradation pathway and in the maintenance of iron homeostasis. The transcriptional induction of HO-1 occurs in response to multiple forms of chemical and physical cellular stress. The cytoprotective functions of HO-1 may be attributed to heme turnover, as well as to beneficial properties of its enzymatic reaction products: biliverdin-IXalpha, iron, and carbon monoxide (CO). Recent studies have demonstrated that HO-1 or CO inhibits stress-induced extrinsic and intrinsic apoptotic pathways in vitro. A variety of signaling molecules have been implicated in the cytoprotection conferred by HO-1/CO, including autophagic proteins, p38 mitogen-activated protein kinase, signal transducer and activator of transcription proteins, nuclear factor-kappaB, phosphatidylinositol 3-kinase/Akt, and others. Enhanced HO-1 expression or the pharmacological application of HO end-products affords protection in preclinical models of tissue injury, including experimental and transplant-associated ischemia/reperfusion injury, promising potential future therapeutic applications.

  18. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: JLiu@kumc.edu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

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

    Directory of Open Access Journals (Sweden)

    Xuanfei Li

    2014-01-01

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

  20. In vivo anti-inflammatory action of eugenol on lipopolysaccharide-induced lung injury.

    Science.gov (United States)

    Magalhães, Clarissa B; Riva, Douglas R; DePaula, Leonardo J; Brando-Lima, Aline; Koatz, Vera Lúcia G; Leal-Cardoso, José Henrique; Zin, Walter A; Faffe, Débora S

    2010-04-01

    Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-kappaB (NF-kappaB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 microg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (DeltaP1) and viscoelastic (DeltaP2) pressures, static elastance (E(st)), and viscoelastic component of elastance (DeltaE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-alpha was determined by ELISA. Lung tissue expression of NF-kappaB was determined by EMSA. DeltaP1, DeltaP2, E(st), and DeltaE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-alpha levels and NF-kappaB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Prevention of Sports Injuries by Marine Omega-3 Fatty Acids.

    Science.gov (United States)

    Bryhn, Morten

    2015-01-01

    Sport injuries are common and costly for the professional athlete, the "weekend warrior," and the community. Acute injuries are treated according to current guidelines with the aim of bringing the athlete back into the arena. These guidelines have not taken into account new scientific results of the inflammatory process following a trauma. The 4 hallmarks of inflammation, namely, pain, swelling, redness, and heat, are results of an adequate inflammatory response with the aim of bringing the affected tissue back to restitution (Latin: restitutio ad integrum). Cooling of the affected limb and anti-inflammatory drugs are widely used but may deter healing. The healing process is governed by fatty acids of the omega-3 and omega-6 series. In order to facilitate healing, these fatty acids have to be present in significant amounts in the affected tissues before the trauma occurs. This is particularly relevant for marine omega-3 fatty acids, which are often running low due to insignificant intake of seafood, common in individuals practicing sports. High-energy sports often lead to head and brain trauma. Continuous head traumata may even result in later mental defects. Saturation of brain cells with omega-3 fatty acids, in particular docosahexaenoic acid (DHA), may facilitate healing after brain trauma, thereby counteracting negative long-term results. The present understanding of a normal inflammatory process leading to restitution will be discussed along with data from recent scientific trials.

  3. [Recovery of Staphylococcus aureus after acid injury in milk products].

    Science.gov (United States)

    Assis, E M; De Carvalho, E P; Asquieri, E R; Robbs, P G

    1994-01-01

    The growth behavior of Staphylococcus aureus in fresh Cheese (Minas and Muzzarella) during their shelf-life was studied. The possible injury of this microorganism caused by the increasing acidity was also investigated. Raw milk was inoculated with 10(6) cells/ml (S. aureus FRIA-100) and the cheese production was performed according to normal procedures. Minas and muzzarella cheese were stored at 7 degrees C for 40 and 60 days, respectively. At 2-3 days intervals, the following analysis were performed: acidity, pH, S. aureus counting using agar Baird Parker by the traditional methods and by the method recommended by the American Public Health Association to evaluate the reparation of injured cells. We had a secure indication of the presence of injured S. aureus when acidity was in the range of 0.7 to 0.8% expressed in lactic acid and when the cycle was 1.3 log higher than the traditional one.

  4. Sustained inflation at birth did not alter lung injury from mechanical ventilation in surfactant-treated fetal lambs.

    Directory of Open Access Journals (Sweden)

    Noah H Hillman

    Full Text Available BACKGROUND: Sustained inflations (SI are used with the initiation of ventilation at birth to rapidly recruit functional residual capacity and may decrease lung injury and the need for mechanical ventilation in preterm infants. However, a 20 second SI in surfactant-deficient preterm lambs caused an acute phase injury response without decreasing lung injury from subsequent mechanical ventilation. HYPOTHESIS: A 20 second SI at birth will decrease lung injury from mechanical ventilation in surfactant-treated preterm fetal lambs. METHODS: The head and chest of fetal sheep at 126±1 day GA were exteriorized, with tracheostomy and removal of fetal lung fluid prior to treatment with surfactant (300 mg in 15 ml saline. Fetal lambs were randomized to one of four 15 minute interventions: 1 PEEP 8 cmH2O; 2 20 sec SI at 40 cmH2O, then PEEP 8 cmH2O; 3 mechanical ventilation with 7 ml/kg tidal volume; or 4 20 sec SI then mechanical ventilation at 7 ml/kg. Fetal lambs remained on placental support for the intervention and for 30 min after the intervention. RESULTS: SI recruited a mean volume of 6.8±0.8 mL/kg. SI did not alter respiratory physiology during mechanical ventilation. Heat shock protein (HSP 70, HSP60, and total protein in lung fluid similarly increased in both ventilation groups. Modest pro-inflammatory cytokine and acute phase responses, with or without SI, were similar with ventilation. SI alone did not increase markers of injury. CONCLUSION: In surfactant treated fetal lambs, a 20 sec SI did not alter ventilation physiology or markers of lung injury from mechanical ventilation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-06-01

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

  6. Rituximab induced lung injury in a case of NHL: Diagnosis and follow up on FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Prathamesh; Lele, Vikram [Jaslok Hospital and Research Centre, Worli (United States); Saikia, Tapan [Prince Aly Khan Hospital, Mumbai (India)

    2012-09-15

    Rituximab induced lung injury is a rare but serious side effect of this agent. We describe the valuable role played by 18F fluorodeoxyglucose positron emission tomography computed tomography (FDG PET CT)in the diagnosis and follow up of this condition in a patient with non Hodgkin's lymphoma (NHL)receiving rituximab. Abnormal uptake of FDG in lungs of patients receiving this drug should be care fully evaluated to diagnose this potentially fatal side effect.

  7. Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement

    DEFF Research Database (Denmark)

    Czermak, B J; Lentsch, A B; Bless, N M;

    1999-01-01

    Complement plays an important role in many acute inflammatory responses. In the current studies it was demonstrated that, in the presence of either C5a or sublytic forms of the complement-derived membrane attack complex (MAC), rat alveolar macrophages costimulated with IgG immune complexes...... increased neutrophil accumulation occurred, as did lung injury. These observations suggest that C5a and MAC function synergistically with a costimulus to enhance chemokine generation and the intensity of the lung inflammatory response....

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

    Institute of Scientific and Technical Information of China (English)

    Guang-Xiu Cai

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

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

    2010-07-31

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

  11. Role of Iron in Hyperoxia-Induced Lung Injury: One Step Forward in

    Directory of Open Access Journals (Sweden)

    Arezoo Ahmadi

    2015-10-01

    Full Text Available Background: An increased oxidative stress in patients under treatment with high concentrations of oxygen (hyperoxia is considered to be one of the major mechanisms of lung injury. Between different mediators, transition metal ions especially iron, by generation of very reactive free radicals play an important role in oxidative stress process. Disruption of normal iron hemostasis has been reported in hyperoxic conditions. So we hypothesized that chelation of iron can reduce hyperoxia- induced lung injury.Methods: Mechanically ventilated patients, who received oxygen with FiO > 0.5 for at least 3 days, underwent bronchoscopy at baseline and 72 hours thereafter. Data from external control cases were collected prospectively to provide a comparative reference group.Iron and Iron-related proteins were measured in lavage fluid and plasma.Results: In 24 patients and in comparison with the results of previous study, Iron concentration decreased significantly in lavage fluid (P<0.001. Reduction of ferritin was not significant in lavage fluid (P: 0.7.Transferrin decreased significantly in plasma (P: 0.01. Acute Physiology And Chronic Health Evaluation (APACHE II (P: 0.006 score decreased significantly after 7 days of follow-up. Conclusion: Deferasirox did not change Iron and Iron-related protein in hyperoxic condition and it just only could be considered along with other supportive measures for better toleration of oxygen therapy.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  13. Paraquat induced lung injury: long-term follow-up of HRCT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Tong; Kim, Hyun Cheol; Bae, Won Kyung; Kim, Il Young; Im, Han Hyek [Soonchunhyang Univ., Chunan (Korea, Republic of)

    2004-03-01

    To determine the long-term follow-up CT findings of paraquat-induced lung injury. Six patients who ingested paraquat underwent sequential follow-up CT scanning during a period of at least six months, and the results were analysed. Scans were obtained 1-6 (mean, 3.3) time during a 7-84 (mean, 25.7) months period, and the findings at 1-2 months, 3-12 months, 1-2 years, 2-3 years and more than above 7 years after poisoning were analyzed. We observed irregular-shaped areas of consolidation with traction bronchiectasis at 1-2 months (5/5), irregular-shaped consolidation and ground-glass opacity (5/5) at 3-12 months, and irregular-shaped consolidations/ground-glass opacity (4/5) and focal honeycombing (1/5) one year later. In the same patients, follow-up CT scans showed that some areas of focal consolidation could not be visualized and the radio-opacity of the lesions had decreased. The HRCT findings of paraquat-induced lung injury were irregular shaped areas of consolidation 1-2 months after ingestion, and irregular-shaped consolidation and ground-glass opacity or focal honeycombing 3-12 months later. At this thim slight improvement was observed.

  14. Toll-like receptor 4-dependent responses to lung injury in a murine model of pulmonary contusion.

    Science.gov (United States)

    Hoth, J Jason; Wells, Jonathan D; Brownlee, Noel A; Hiltbold, Elizabeth M; Meredith, J Wayne; McCall, Charles E; Yoza, Barbara K

    2009-04-01

    Blunt chest trauma resulting in pulmonary contusion with an accompanying acute inflammatory response is a common but poorly understood injury. We previously demonstrated that toll-like receptor 2 (TLR-2) participates in the inflammatory response to lung injury. We hypothesized that the TLR-4, in an MyD88-dependent manner, may also participate in the response to lung injury. To investigate this, we used a model of pulmonary contusion in the mouse that is similar to that observed clinically in humans and evaluated postinjury lung function, pulmonary neutrophil recruitment, and the systemic innate immune response. Comparisons were made between wild-type mice and mice deficient in TLR-4 or MyD88. We found TLR-4-dependent responses to pulmonary contusion that include hypoxemia, edema, and neutrophil infiltration. Increased expression of IL-6 and chemokine (C-X-C motif) ligand 1 in the bronchoalveolar lavage and serum was also dependent on TLR-4 activation. We further demonstrated that these responses to pulmonary contusion were dependent on MyD88, an adapter protein in the signal transduction pathway mediated by TLRs. These results show that TLRs have a primary role in the response to acute lung injury. Lung inflammation and systemic innate immune responses are dependent on TLR activation by pulmonary contusion.

  15. Selection of Reference Genes for Gene Expression Studies related to lung injury in a preterm lamb model.

    Science.gov (United States)

    Pereira-Fantini, Prue M; Rajapaksa, Anushi E; Oakley, Regina; Tingay, David G

    2016-05-23

    Preterm newborns often require invasive support, however even brief periods of supported ventilation applied inappropriately to the lung can cause injury. Real-time quantitative reverse transcriptase-PCR (qPCR) has been extensively employed in studies of ventilation-induced lung injury with the reference gene 18S ribosomal RNA (18S RNA) most commonly employed as the internal control reference gene. Whilst the results of these studies depend on the stability of the reference gene employed, the use of 18S RNA has not been validated. In this study the expression profile of five candidate reference genes (18S RNA, ACTB, GAPDH, TOP1 and RPS29) in two geographical locations, was evaluated by dedicated algorithms, including geNorm, Normfinder, Bestkeeper and ΔCt method and the overall stability of these candidate genes determined (RefFinder). Secondary studies examined the influence of reference gene choice on the relative expression of two well-validated lung injury markers; EGR1 and IL1B. In the setting of the preterm lamb model of lung injury, RPS29 reference gene expression was influenced by tissue location; however we determined that individual ventilation strategies influence reference gene stability. Whilst 18S RNA is the most commonly employed reference gene in preterm lamb lung studies, our results suggest that GAPDH is a more suitable candidate.

  16. Role of p53–fibrinolytic system cross-talk in the regulation of quartz-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Bhandary, Yashodhar P.; Shetty, Shwetha K.; Marudamuthu, Amarnath S. [Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States); Fu, Jian [Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States); Center for Research on Environmental Disease and Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Pinson, Barbara M. [Occupational Medicine, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States); Center for Research on Environmental Disease and Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Levin, Jeffrey [Occupational Medicine, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States); Shetty, Sreerama, E-mail: sreerama.shetty@uthct.edu [Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States)

    2015-03-01

    Silica is the major component of airborne dust generated by wind, manufacturing and/or demolition. Chronic occupational inhalation of silica dust containing crystalline quartz is by far the predominant form of silicosis in humans. Silicosis is a progressive lung disease that typically arises after a very long latency and is a major occupational concern with no known effective treatment. The mechanism of silicosis is not clearly understood. However, silicosis is associated with increased cell death, expression of redox enzymes and pro-fibrotic cytokines and chemokines. Since alveolar epithelial cell (AEC) death and disruption of alveolar fibrinolysis is often associated with both acute and chronic lung injuries, we explored whether p53-mediated changes in the urokinase-type plasminogen activator (uPA) system contributes to silica-induced lung injury. We further sought to determine whether caveolin-1 scaffolding domain peptide (CSP), which inhibits p53 expression, mitigates lung injury associated with exposure to silica. Lung tissues and AECs isolated from wild-type (WT) mice exposed to silica exhibit increased apoptosis, p53 and PAI-1, and suppression of uPA expression. Treatment of WT mice with CSP inhibits PAI-1, restores uPA expression and prevents AEC apoptosis by suppressing p53, which is otherwise induced in mice exposed to silica. The process involves CSP-mediated inhibition of serine-15 phosphorylation of p53 by inhibition of protein phosphatase 2A-C (PP2A-C) interaction with silica-induced caveolin-1 in AECs. These observations suggest that changes in the p53–uPA fibrinolytic system cross-talk contribute to lung injury caused by inhalation of silica dust containing crystalline quartz and is protected by CSP by targeting this pathway. - Highlights: • Chronic exposure to quartz dusts is a major cause of lung injury and silicosis. • The survival of patients with silicosis is bleak due to lack of effective treatments. • This study defines a new role of

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

    Institute of Scientific and Technical Information of China (English)

    Wang Lei; Yuan Ruixia; Yao Chengyue; Wu Qingping; Marie Christelle; Xie Wanli; Zhang Xingcai

    2014-01-01

    Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury.Inflammation is associated with an oxidative stress reaction,which is produced in the development of airway inflammation,and which has positive feedback on inflammation itself.Resolvin D1 can reduce the infiltration of neutrophils,regulate cytokine levels and reduce the inflammation reaction,and thereby promote the resolution of inflammation.The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide (LPS)-induced acute lung injury.Methods LPS (3 mg/kg) was used to induce the acute lung injury model.Pretreatment resolvin D1 (100 ng/mouse) was given to mice 30 minutes before inducing acute lung injury.Mice were observed at 6 hours,12 hours,1 day,2 days,3 days,4 days and 7 days after LPS was administrated,then they were humanely sacrificed.We collected bronchoalveolar lavage fluid (BALF) and the lung tissues for further analysis.Paraffin section and HE staining of the lung tissues were made for histopathology observations.Parts of the lung tissues were evaluated for wet-to-dry (W/D) weight ratio.tumor necrosis factor (TNF)-α,inter leukin (IL)-1β,IL-10 and myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA).A lipid peroxidation malondialdehyde (MDA) assay kit was used to detect MDA.A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase (SOD).We determined the apoptosis of neutrophils by Flow Cytometry.A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase (HO)-1.Results Pretreatment with resolvin D1 reduced the pathological damage in the lung,decreased the recruitment of neutrophils and stimulated their apoptosis.It markedly decreased the expressions of TNF

  18. Retinoic acid amide inhibits JAK/STAT pathway in lung cancer which leads to apoptosis.

    Science.gov (United States)

    Li, Hong-Xing; Zhao, Wei; Shi, Yan; Li, Ya-Na; Zhang, Lian-Shuang; Zhang, Hong-Qin; Wang, Dong

    2015-11-01

    Small cell lung cancer (SCLC) accounts for 12 to 16% of lung neoplasms and has a high rate of metastasis. The present study demonstrates the antiproliferative effect of retinoic acid amide in vitro and in vivo against human lung cancer cells. The results from MTT assay showed a significant growth inhibition of six tested lung cancer cell lines and inhibition of clonogenic growth at 30 μM. Retinoic acid amide also leads to G2/M-phase cell cycle arrest and apoptosis of lung cancer cells. It caused inhibition of JAK2, STAT3, and STAT5, increased the level of p21WAF1, and decreased cyclin A, cyclin B1, and Bcl-XL expression. Retinoic acid amide exhibited a synergistic effect on antiproliferative effects of methotrexate in lung cancer cells. In lung tumor xenografts, the tumor volume was decreased by 82.4% compared to controls. The retinoic acid amide-treated tumors showed inhibition of JAK2/STAT3 activation and Bcl-XL expression. There was also increase in expression of caspase-3 and caspase-9 in tumors on treatment with retinoic acid amide. Thus, retinoic acid amide exhibits promising antiproliferative effects against human lung cancer cells in vitro and in vivo and enhances the antiproliferative effect of methotrexate.

  19. Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury in Mouse Model.

    Directory of Open Access Journals (Sweden)

    Xing Chen

    Full Text Available To investigate the protective role of the sonic hedgehog (SHH signaling associated with a lipopolysaccharide (LPS-induced acute lung injury (ALI in a mouse model.Male BALB/c mice were randomly divided into four groups: control, LPS, LPS-cyclopamine group and cyclopamine group. ALI was induced by LPS ip injection (5 mg/kg. The sonic hedgehog inhibitor cyclopamine (50 mg/kg was given to the LPS-cyclopamine group at 30 min after LPS injection as well as normal mice as control. Lung injury was observed histologically in hematoxylin and eosin (HE stained tissue sections, semi-quantified by lung tissue injury score, and the lung tissue mass alteration was measured by wet to dry weight ratio (W/D. mRNA expression levels of TNF-α, SHH, Patched (PTC and GLI1 in lung tissue were studied with real time quantitative PCR (RT-PCR, while the protein expression of SHH and GLI1 was determined by western blot analysis.Lung tissue injury score, thickness of alveolar septa, W/D, and TNF-α mRNA expression levels were significantly higher in the ALI mice than the normal mice (P<0.05. The mRNA expression levels of SHH, PTC, and GLI1 in the ALI mice were significantly higher at 12h and 24h after LPS injection, but not at the 6h time point. Protein production of SHH and GLI1 at 6h, 12h, and 24h in the lungs of ALI mice significantly increased, in a time-dependent manner, compared with that in normal mice. Cyclopamine alone has no effect on pathological changes in normal mice. Intervention with cyclopamine in ALI mice led to a reduction in mRNA levels of SHH, PTC, and GLI1 as well as SHH and GLI1 protein levels; meanwhile, the pathological injury scores of lung tissues, thickness of alveolar septa, W/D, and mRNA expression levels of TNF-α increased compared with mice receiving LPS only.The SHH signaling pathway was activated in response to LPS-induced ALI, and up-regulation of SHH expression could alleviate lung injury and be involved in the repair of injured lung

  20. Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effects of ursodeoxycholic acid (UDCA) on chenodeoxycholic acid (CDCA)-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS: Liver injury was induced in hamsters by administration of 0.5% (w/w) CDCA in their feed for 7 d.UDCA (50 mg/kg and 150 mg/kg) was administered for the last 3 d of the experiment.RESULTS: At the end of the experiment, serum alanine aminotransferase (ALT) increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid (LCA). UDCA (50 mg/kg and 150 mg/kg) improved liver histology, with a significant decrease (679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ± 35.5 U/L, respectively, P < 0.01) in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION: The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.

  1. Pulmonary mechanic and lung histology injury induced by Crotalus durissus terrificus snake venom.

    Science.gov (United States)

    Nonaka, Paula Naomi; Amorim, César Ferreira; Paneque Peres, Ana Claudia; E Silva, César Augusto Melo; Zamuner, Stella R; Ribeiro, Wellington; Cogo, José Carlos; Vieira, Rodolfo P; Dolhnikoff, Marisa; de Oliveira, Luis Vicente Franco

    2008-06-01

    In the present work we investigated the effects of Crotalus durissus terrificus venom (CdtV) on the pulmonary mechanic events [static and dynamic elastance, resistive (DeltaP1) and viscoelastic pressures (DeltaP2)] and histology after intramuscular injection of saline solution (control) or venom (0.6 microg/g). The static and dynamic elastance values were increased significantly after 3 h of venom inoculation, but were reduced at control values in the other periods studied. The DeltaP1 values that correspond to the resistive properties of lung tissue presented a significant increase after 6h of CdtV injection, reducing to basal levels 12h after the venom injection. In DeltaP2 analysis, correspondent to viscoelastic components, an increase occurred 12 h after the venom injection, returning to control values at 24 h. CdtV also caused an increase of leukocytes recruitment (3-24 h) to the airways wall as well as to the lung parenchyma. In conclusion, C. durissus terrificus rattlesnake venom leads to lung injury which is reverted, after 24 h of inoculation.

  2. A trial of nebulised heparin to limit lung injury following cardiac surgery.

    Science.gov (United States)

    Dixon, B; Smith, R; Santamaria, J D; Orford, N R; Wakefield, B J; Ives, K; McKenzie, R; Zhang, B; Yap, C H

    2016-01-01

    Cardiac surgery with cardiopulmonary bypass triggers an acute inflammatory response in the lungs. This response gives rise to fibrin deposition in the microvasculature and alveoli of the lungs. Fibrin deposition in the microvasculature increases alveolar dead space, while fibrin deposition in alveoli causes shunting. We investigated whether prophylactic nebulised heparin could limit this form of lung injury. We undertook a single-centre double-blind randomised trial. Forty patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomised to prophylactic nebulised heparin (50,000 U) or placebo. The primary endpoint was the change in arterial oxygen levels over the operative period. Secondary endpoints included end-tidal CO₂, the alveolar dead space fraction and bleeding complications. We found nebulised heparin did not improve arterial oxygen levels. Nebulised heparin was, however, associated with a lower alveolar dead space fraction (P heparin was not associated with bleeding complications. In conclusion, prophylactic nebulised heparin did not improve oxygenation, but was associated with evidence of better alveolar perfusion and CO₂elimination at the end of surgery.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-07-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

    Science.gov (United States)

    Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Albayrak, Abdulmecit; Karakus, Emre; Polat, Beyzagul; Unal, Deniz; Atamanalp, Sabri S; Aksak, Selina; Gundogdu, Cemal

    2013-10-01

    Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality.

  6. Matrine Attenuates COX-2 and ICAM-1 Expressions in Human Lung Epithelial Cells and Prevents Acute Lung Injury in LPS-Induced Mice

    Directory of Open Access Journals (Sweden)

    Chian-Jiun Liou

    2016-01-01

    Full Text Available Matrine is isolated from Sophora flavescens and shows anti-inflammatory effects in macrophages. Here we evaluated matrine’s suppressive effects on cyclooxygenase 2 (COX-2 and intercellular adhesion molecule-1 (ICAM-1 expressions in lipopolysaccharide- (LPS- stimulated human lung epithelial A549 cells. Additionally, BALB/c mice were given various matrine doses by intraperitoneal injection, and then lung injury was induced via intratracheal instillation of LPS. In LPS-stimulated A549 cells, matrine inhibited the productions of interleukin-8 (IL-8, monocyte chemotactic protein-1, and IL-6 and decreased COX-2 expression. Matrine treatment also decreased ICAM-1 protein expression and suppressed the adhesion of neutrophil-like cells to inflammatory A549 cells. In vitro results demonstrated that matrine significantly inhibited mitogen-activated protein kinase phosphorylation and decreased nuclear transcription factor kappa-B subunit p65 protein translocation into the nucleus. In vivo data indicated that matrine significantly inhibited neutrophil infiltration and suppressed productions of tumor necrosis factor-α and IL-6 in mouse bronchoalveolar lavage fluid and serum. Analysis of lung tissue showed that matrine decreased the gene expression of proinflammatory cytokines, chemokines, COX-2, and ICAM-1. Our findings suggest that matrine improved lung injury in mice and decreased the inflammatory response in human lung epithelial cells.

  7. Matrine Attenuates COX-2 and ICAM-1 Expressions in Human Lung Epithelial Cells and Prevents Acute Lung Injury in LPS-Induced Mice.

    Science.gov (United States)

    Liou, Chian-Jiun; Lai, You-Rong; Chen, Ya-Ling; Chang, Yi-Hsien; Li, Zih-Ying; Huang, Wen-Chung

    2016-01-01

    Matrine is isolated from Sophora flavescens and shows anti-inflammatory effects in macrophages. Here we evaluated matrine's suppressive effects on cyclooxygenase 2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) expressions in lipopolysaccharide- (LPS-) stimulated human lung epithelial A549 cells. Additionally, BALB/c mice were given various matrine doses by intraperitoneal injection, and then lung injury was induced via intratracheal instillation of LPS. In LPS-stimulated A549 cells, matrine inhibited the productions of interleukin-8 (IL-8), monocyte chemotactic protein-1, and IL-6 and decreased COX-2 expression. Matrine treatment also decreased ICAM-1 protein expression and suppressed the adhesion of neutrophil-like cells to inflammatory A549 cells. In vitro results demonstrated that matrine significantly inhibited mitogen-activated protein kinase phosphorylation and decreased nuclear transcription factor kappa-B subunit p65 protein translocation into the nucleus. In vivo data indicated that matrine significantly inhibited neutrophil infiltration and suppressed productions of tumor necrosis factor-α and IL-6 in mouse bronchoalveolar lavage fluid and serum. Analysis of lung tissue showed that matrine decreased the gene expression of proinflammatory cytokines, chemokines, COX-2, and ICAM-1. Our findings suggest that matrine improved lung injury in mice and decreased the inflammatory response in human lung epithelial cells.

  8. The effect of low level laser therapy on ventilator-induced lung injury in mice (Conference Presentation)

    Science.gov (United States)

    Szabari, Margit V.; Miller, Alyssa J.; Hariri, Lida P.; Hamblin, Michael R.; Musch, Guido; Stroh, Helene; Suter, Melissa J.

    2016-03-01

    Although mechanical ventilation (MV) is necessary to support gas exchange in critically ill patients, it can contribute to the development of lung injury and multiple organ dysfunction. It is known that high tidal volume (Vt) MV can cause ventilator-induced lung injury (VILI) in healthy lungs and increase the mortality of patients with Acute Respiratory Distress Syndrome. Low level laser therapy (LLLT) has demonstrated to have anti-inflammatory effects. We investigated whether LLLT could alleviate inflammation from injurious MV in mice. Adult mice were assigned to 2 groups: VILI+LLLT group (3 h of injurious MV: Vt=25-30 ml/kg, respiratory rate (RR)=50/min, positive end-expiratory pressure (PEEP)=0 cmH20, followed by 3 h of protective MV: Vt=9 ml/kg, RR=140/min, PEEP=2 cmH20) and VILI+no LLLT group. LLLT was applied during the first 30 min of the MV (810 nm LED system, 5 J/cm2, 1 cm above the chest). Respiratory impedance was measured in vivo with forced oscillation technique and lung mechanics were calculated by fitting the constant phase model. At the end of the MV, bronchoalveolar lavage (BAL) was performed and inflammatory cells counted. Lungs were removed en-bloc and fixed for histological evaluation. We hypothesize that LLLT can reduce lung injury and inflammation from VILI. This therapy could be translated into clinical practice, where it can potentially improve outcomes in patients requiring mechanical ventilation in the operating room or in the intensive care units.

  9. Extracorporeal gas exchange with the DeltaStream rotary blood pump in experimental lung injury.

    Science.gov (United States)

    Dembinski, Rolf; Kopp, Rüdger; Henzler, Dietrich; Hochhausen, Nadine; Oslender, Nicole; Max, Martin; Rossaint, Rolf; Kuhlen, Ralf

    2003-06-01

    In most severe cases of the acute respiratory distress syndrome, veno-venous extracorporeal membrane oxygenation (ECMO) can be used to facilitate gas exchange. However, the clinical use is limited due to the size and the concomitant risk of severe adverse events of conventionally-used centrifugal blood pumps with high extracorporeal blood volumes. The DeltaStream blood pump is a small-sized rotary blood pump that may reduce extracorporeal blood volume, foreign surfaces, contact activation of the coagulation system, and blood trauma. The aim of the present study was to test the safety and efficacy of the DeltaStream pump for ECMO in animals with normal lung function and experimental acute lung injury (ALI). Therefore, veno-venous ECMO was performed for 6 hours in mechanically ventilated pigs with normal lung function (n=6) and with ALI induced by repeated lung lavage (n=6) with a blood flow of 30% of the cardiac output. Gas flow with a FiO2 of 1.0 was set to equal blood flow. With a mean activated clotting time of 121 +/- 22 s, no circulatory impairment or thrombus formation was revealed during ECMO. Furthermore, free plasma Hb did not increase. In controls, hemodynamics and gas exchange remained unchanged. In animals with ALI, hemodynamics remained stable and gas transfer across the extracorporeal oxygenators was optimal, but only in 2 animals was a marked increase in PaO2 observed. CO2 removal was efficacious in all animals. We concluded that the DeltaStream blood pump may be used for veno-venous ECMO without major blood damage or hemodynamic impairment.

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

    Science.gov (United States)

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

    2016-12-01

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

  11. A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior

    Directory of Open Access Journals (Sweden)

    Tomlinson Stephen

    2010-02-01

    Full Text Available Abstract Background Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment. Presentation of the hypothesis Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited. Testing the hypothesis CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated. Implications of the hypothesis CR2 targeting complement inhibitors

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

    OpenAIRE

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

    1990-01-01

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

  13. Alveolocapillary membrane permeability in experimental model of ventilator induced lung injury

    Directory of Open Access Journals (Sweden)

    Наталья Александровна Решетняк

    2016-01-01

    Full Text Available Aim: to assess alveocapillary membrane permeability for the whole protein, middle mole