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Sample records for acute lung dysfunction

  1. 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...

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Keith Meyer

    2015-01-01

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

  4. Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Rudolf eLucas

    2013-08-01

    Full Text Available The integrity of epithelial and endothelial barriers in the lower airspaces of the lungs has to be tightly regulated, in order to prevent leakage and to assure efficient gas exchange between the alveoli and capillaries. Both G- and G+ bacterial toxins, such as LPS and pneumolysin, respectively, can be released in high concentrations within the pulmonary compartments upon antibiotic treatment of patients suffering from acute respiratory distress syndrome (ARDS or severe pneumonia. These toxins are able to impair endothelial barrier function, either directly, or indirectly, by induction of pro-inflammatory mediators and neutrophil sequestration. Toxin-induced endothelial hyperpermeability can involve myosin light chain phosphorylation and/or microtubule rearrangement. Endothelial nitric oxide synthase (eNOS was proposed to be a guardian of basal barrier function, since eNOS knock-out mice display an impaired expression of inter-endothelial junction proteins and as such an increased vascular permeability, as compared to wild type mice. The enzyme arginase, the activity of which can be regulated by the redox status of the cell, exists in two isoforms - arginase 1 (cytosolic and arginase 2 (mitochondrial - both of which can be expressed in lung microvascular endothelial cells. Upon activation, arginase competes with eNOS for the substrate L-arginine, as such impairing eNOS-dependent NO generation and promoting ROS generation by the enzyme. This mini-review will discuss recent findings regarding the interaction between bacterial toxins and arginase during acute lung injury and will as such address the role of arginase in bacterial toxin-induced pulmonary endothelial barrier dysfunction.

  5. Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in models of acute lung injury.

    Science.gov (United States)

    Lucas, Rudolf; Czikora, Istvàn; Sridhar, Supriya; Zemskov, Evgeny A; Oseghale, Aluya; Circo, Sebastian; Cederbaum, Stephen D; Chakraborty, Trinad; Fulton, David J; Caldwell, Robert W; Romero, Maritza J

    2013-01-01

    The integrity of epithelial and endothelial barriers in the lower airspaces of the lungs has to be tightly regulated, in order to prevent leakage and to assure efficient gas exchange between the alveoli and capillaries. Both G(-) and G(+) bacterial toxins, such as lipopolysaccharide and pneumolysin, respectively, can be released in high concentrations within the pulmonary compartments upon antibiotic treatment of patients suffering from acute respiratory distress syndrome (ARDS) or severe pneumonia. These toxins are able to impair endothelial barrier function, either directly, or indirectly, by induction of pro-inflammatory mediators and neutrophil sequestration. Toxin-induced endothelial hyperpermeability can involve myosin light chain phosphorylation and/or microtubule rearrangement. Endothelial nitric oxide synthase (eNOS) was proposed to be a guardian of basal barrier function, since eNOS knock-out mice display an impaired expression of inter-endothelial junction proteins and as such an increased vascular permeability, as compared to wild type mice. The enzyme arginase, the activity of which can be regulated by the redox status of the cell, exists in two isoforms - arginase 1 (cytosolic) and arginase 2 (mitochondrial) - both of which can be expressed in lung microvascular endothelial cells. Upon activation, arginase competes with eNOS for the substrate l-arginine, as such impairing eNOS-dependent NO generation and promoting reactive oxygen species generation by the enzyme. This mini-review will discuss recent findings regarding the interaction between bacterial toxins and arginase during acute lung injury and will as such address the role of arginase in bacterial toxin-induced pulmonary endothelial barrier dysfunction. PMID:23966993

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

    Directory of Open Access Journals (Sweden)

    M.F.R. Silva

    1998-03-01

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

  7. 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.

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

    OpenAIRE

    M.F.R. Silva; P.H.N. Saldiva

    1998-01-01

    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 l...

  9. Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2 trial: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    McAuley Daniel F

    2012-09-01

    Full Text Available Abstract Background Acute lung injury (ALI is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2 trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI. Methods/Design Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1:1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms

  10. Pathophysiology of pulmonary hypertension in acute lung injury

    OpenAIRE

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

    2012-01-01

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

  11. Right Ventricular Dysfunction in Chronic Lung Disease

    OpenAIRE

    Kolb, Todd M.; Hassoun, Paul M.

    2012-01-01

    Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, ex...

  12. 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.

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

    International Nuclear Information System (INIS)

    Reactive O2 species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O2 species involved in lung O2 metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O2 consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H2O2 and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O2 consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O2 consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H2O2 production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O2 consumption may account for an augmented Nox activity, causing an increased O2·− production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O2 species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O2 consumption. • Exposure to ROFA produces alterations in mitochondrial function. • ΔΨm decrease in state 3 may be responsible

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-01

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

  15. Acute cognitive dysfunction after hip fracture

    DEFF Research Database (Denmark)

    Bitsch, M S; Foss, N B; Kristensen, B B;

    2006-01-01

    Patients undergoing hip fracture surgery often experience acute post-operative cognitive dysfunction (APOCD). The pathogenesis of APOCD is probably multifactorial, and no single intervention has been successful in its prevention. No studies have investigated the incidence of APOCD after hip fract...... fracture surgery in an optimized, multimodal, peri-operative rehabilitation regimen....

  16. Biomarkers in Acute Lung Injury

    OpenAIRE

    Bhargava, Maneesh; Wendt, Chris

    2012-01-01

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

  17. 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.

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

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    Bhatia R

    2003-04-01

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

  19. Acute renal dysfunction in liver diseases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (MRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.

  20. Experimental acute lung injury induces multi-organ epigenetic modifications in key angiogenic genes implicated in sepsis-associated endothelial dysfunction

    OpenAIRE

    Bomsztyk, Karol; Mar, Daniel; An, Dowon; Sharifian, Roya; Mikula, Michal; Gharib, Sina A; Altemeier, William A.; Liles, W. Conrad; Denisenko, Oleg

    2015-01-01

    Introduction The Tie2/angiopoietin (Tie2/Ang) and vascular endothelial growth factor receptor-ligand systems (VEGFR/VEGF) are recognized to play important roles in the regulation of microvascular endothelial function. Downregulation of these genes during sepsis has been implicated in the pathogenesis of sepsis-related microvascular leak and multiple organ dysfunction syndrome. Mechanisms responsible for dysregulation of angiogenic genes in sepsis are poorly defined. Methods Western blot, reve...

  1. Acute renal dysfunction following hip fracture.

    Science.gov (United States)

    Bennet, Simon J; Berry, Olivia M B; Goddard, Jane; Keating, John F

    2010-04-01

    We investigated the incidence, risk factors and outcome of acute renal dysfunction (ARD) in patients with a fractured neck of femur. 170 consecutive patients were prospectively included in the Scottish Hip Fracture Audit database and retrospectively analysed. Historically, lack of consensus definition has hindered accurate reporting of ARD. ARD was defined using the 'RIFLE' criteria. 27 patients (16%) developed ARD. Risk factors were male sex, vascular disease, hypertension, diabetes, chronic kidney disease and pre-morbid use of nephrotoxic medications (pARD group 19%, 22% and 41% respectively, versus 0%, 4% and 13% in the non-ARD group (pARD group. Pre- and post-operative complications were 12 and 5 times more frequent respectively in the ARD group (p<0.01). Awareness of risk factors and serial measurements of renal function allow early identification and focused monitoring of these patients. PMID:19729159

  2. 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.

  3. Chronic lung allograft dysfunction after lung transplantation: novel insights into immunological mechanisms

    NARCIS (Netherlands)

    Budding, K.

    2016-01-01

    Lung transplantation (LTx) is the final treatment option for patients suffering from end-stage lung diseases. Survival after LTx is hampered by the development of chronic lung allograft dysfunction which presents itself in an obstructive form as the bronchiolitis obliterans syndrome (BOS). BOS is ha

  4. Primary Graft Dysfunction after LungTransplantation

    OpenAIRE

    Kaaij, Niels

    2014-01-01

    markdownabstract__Abstract__ The human body requires oxygen to perform aerobic processes 1-3. The lungs are the respiratory organs that not only supply oxygen to the blood, but also remove carbon dioxide from the body. The right lung is most commonly made up of three lobes (superior, middle and inferior) relatively separated by fissures, while the left lung consists of two lobes (superior and inferior). Every lobe is again divided in several bronchopulmonary segments, which are the largest su...

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

    OpenAIRE

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

    2008-01-01

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

  6. Resolution of acute inflammation in the lung.

    Science.gov (United States)

    Levy, Bruce D; Serhan, Charles N

    2014-01-01

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

  7. Acute exacerbations of fibrotic interstitial lung disease.

    Science.gov (United States)

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

    2011-03-01

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

  8. Obstructive lung disease in acute medical patients.

    OpenAIRE

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

    2008-01-01

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

  9. Nebulized Pentamidine-Induced Acute Renal Allograft Dysfunction

    Directory of Open Access Journals (Sweden)

    Siddhesh Prabhavalkar

    2013-01-01

    Full Text Available Acute kidney injury (AKI is a recognised complication of intravenous pentamidine therapy. A direct nephrotoxic effect leading to acute tubular necrosis has been postulated. We report a case of severe renal allograft dysfunction due to nebulised pentamidine. The patient presented with repeated episodes of AKI without obvious cause and acute tubular necrosis only on renal histology. Nebulised pentamidine was used monthly as prophylaxis for Pneumocystis jirovecii pneumonia, and administration preceded the creatinine rise on each occasion. Graft function stabilised following discontinuation of the drug. This is the first report of nebulized pentamidine-induced reversible nephrotoxicity in a kidney allograft. This diagnosis should be considered in a case of unexplained acute renal allograft dysfunction.

  10. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

    OpenAIRE

    Moustafa Elsheshtawy; Priatharsini Sriganesh; Vasudev Virparia; Falgun Patel; Ashok Khanna

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

  11. 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.

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

    International Nuclear Information System (INIS)

    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

  13. Acute lung injury and acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Ragaller Maximillian

    2010-01-01

    Full Text Available Every year, more information accumulates about the possibility of treating patients with acute lung injury or acute respiratory distress syndrome with specially designed mechanical ventilation strategies. Ventilator modes, positive end-expiratory pressure settings, and recruitment maneuvers play a major role in these strategies. However, what can we take from these experimental and clinical data to the clinical practice? In this article, we discuss substantial options of mechanical ventilation together with some adjunctive therapeutic measures, such as prone positioning and inhalation of nitric oxide.

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

    OpenAIRE

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F.; Nielsen, Michael B.; Mortensen, Jann

    2012-01-01

    Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation–perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was car...

  15. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

    Directory of Open Access Journals (Sweden)

    Moustafa Elsheshtawy

    2016-01-01

    Full Text Available Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

  16. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction.

    Science.gov (United States)

    Elsheshtawy, Moustafa; Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools. PMID:27119030

  17. Monitorization of Acute Brain Dysfunction in Critical Illness

    OpenAIRE

    Günseli Orhun; Figen Esen

    2016-01-01

    Acute brain dysfunction is a clinical condition which is commonly observed in intensive care units and exhibits neurological changes ranging from delirium to coma. Typically observed during sepsis in critical patients, this syndrome is also named as “sepsis-associated encephalopathy” and this situation is of significance since it is related to mortality, increase of morbidity and long-term cognitive impairment. Monitorization of brain functions in critically ill patients should be commenced w...

  18. Acute behavioural dysfunctions following exposure to γ-rays

    International Nuclear Information System (INIS)

    Exposure to ionizing radiations (IR) has been reported to have many ill effects. These are manifested immediately after exposure and may persist or develop long after the incident. The severity and manifestation is dependent on the absorbed dose and type of the IR. These have been reported extensively in human subjects; especially among the victims of the accidental exposure and radiotherapy patients. Additionally, there have been a plethora of studies in animal models which support these findings, and are being used to test radio-mitigative or radio-protective strategies. The vulnerability of neuronal tissue to IR is well known, however the acute dose-dependent behavioural consequences have yet to be understood. Thus, our laboratory has been trying to decipher the dose-dependent behavioural dysfunctions which have occurred 24-72 hours post IR exposure and possible radio-protective strategies. We are utilizing mouse models of studying the behavioural processes, in a test battery conceptualized to study the affective and cognitive skills as well as motor skills of the animals. Additionally, we have observed cellular damage to different areas of the brain and subsequent correlations to behavioural dysfunctions. This has being carried out by using single cell gel electrophoresis (SCGE) and Diffusion Tensor Imaging (DTI). The findings show that after exposure to sub-lethal γ-rays, there are significant changes that occur in all the behavioural parameters. The most sensitive area has been found to be the Hippocampus as visualized by DTI and the SCGE. Consequently, short term and long term memory functions have been shown to be disrupted within 24-72 hours of exposure. Acute dysfunctions of affective functions have also been demonstrated to materialise within 24 hours post exposure. Unexpectedly, the behavioural dysfunctions were seen to be dose independent. Thus, this study provides a foundation to help decipher the acute behavioural manifestations of IR exposure

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

    Directory of Open Access Journals (Sweden)

    Cuzzocrea Salvatore

    2007-10-01

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

  20. Lipasuria in acute pancreatitis: result of tubular dysfunction?

    Science.gov (United States)

    Muench, R; Buehler, H; Kehl, O; Ammann, R

    1987-01-01

    Lipase, in contrast to amylase, is completely reabsorbed by the proximal tubules after glomerular filtration. Therefore, no lipase is detectable in the unconcentrated urine according to the current opinion. The handling of lipase (detected with an enzyme-immunoassay) by the kidney was investigated in comparison with creatinine, amylase, and beta-2-microglobulin by clearance studies in acute pancreatitis (n = 10), burn injury (n = 4), glomerular proteinuria (n = 8), and controls without evidence of pancreatic or renal diseases (n = 5). In initial stages of acute pancreatitis a measurable clearance of lipase (mean: 49.6 microliters/min, range: 0.5-234) was found in association with corresponding increased clearances of beta-2-microglobulin (mean: 10.5 ml/min, range: 0.02-58.9) and of amylase (mean: 8.9 ml/min, range: 2.4-22.6) in nine of ten patients. This finding is consistent with a defect of tubular function. However, regression analysis failed to show a significant correlation between lipase and beta-2-microglobulin clearance. Repeated measurements during the course of pancreatitis in seven patients showed reversibility of tubular dysfunction. In patients with burn injury a similar elevation of clearances of beta-2-microglobulin and of amylase was found, but tubular dysfunction in this condition was not associated with lipasuria. In glomerular proteinuria a lipase clearance was found in two of five cases with moderate, and in the other three cases with severe impairment of creatinine clearance. beta-2-microglobulin clearance was normal in the former and only slightly elevated in the latter group. In conclusion lipase is measurable in the urine of most patients with acute pancreatitis as a result of a reversible tubular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Attach importance to the early diagnosis and treatment of acute coagulation dysfunction after major war trauma

    OpenAIRE

    Li, Jie-Shou; Li, You-sheng

    2013-01-01

    Coagulation dysfunction after major war trauma is conventionally attributed to consumption and dilution of coagulation factors. However, recent studies have identified an acute coagulation dysfunction at the early stage after trauma. This coagulation dysfunction due to endogenous coagulation disturbance at the early stage after trauma is called acute traumatic coagulation dysfunction (ATCD), and the patients with ATCD would have an increased complication rate and mortality. Standard coagulati...

  2. 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

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

    Institute of Scientific and Technical Information of China (English)

    Emmanouil Petrou; Vasiliki Karali; Vasiliki Vartela

    2015-01-01

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

  4. 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....

  5. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation.

    Science.gov (United States)

    Budding, Kevin; van de Graaf, Eduard A; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M; Luijk, Bart D; Oudijk, Erik-Jan D; van Kessel, Diana A; Grutters, Jan C; Hack, C Erik; Otten, Henderikus G

    2016-05-24

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx.

  6. 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....

  7. 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

  8. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction after Lung Transplantation

    NARCIS (Netherlands)

    Budding, Kevin; Van De Graaf, Eduard A.; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M.; Luijk, Bart D.; Oudijk, Erik Jan D; Van Kessel, Diana A.; Grutters, Jan C.; Hack, C. Erik; Otten, Henderikus G.

    2016-01-01

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung dis

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

    OpenAIRE

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

    2013-01-01

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

  10. Therapeutic Modulation of Coagulation and Fibrinolysis in Acute Lung Injury and the Acute Respiratory Distress Syndrome

    OpenAIRE

    Sebag, Sara C.; Bastarache, Julie A.; Ware, Lorraine B.

    2011-01-01

    Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by excessive intra-alveolar fibrin deposition, driven, at least in part by inflammation. The imbalance between activation of coagulation and inhibition of fibrinolysis in patients with ALI/ARDS favors fibrin formation and appears to occur both systemically and in the lung and airspace. Tissue factor (TF), a key mediator of the activation of coagulation in the lung, has been implicated in the pathogenesis ...

  11. Organ dysfunction as a risk factor for early severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jan De Waele; S.Blot; Francis Colardyn

    2004-01-01

    @@ To the Editor: We read with interest the review paper by Tao et al.[1] on the topic of early severe acute pancreatitis (EASP, defined as severe acute pancreatitis according to the Altanta criteria[2], with organ dysfunction within 72 h after the start of symptoms) in a recent issue of the World Journal of Gastroenterology. It addresses an important problem in patients with severe acute pancreatitis,namely early organ dysfunction and its effect on outcomes.

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

    OpenAIRE

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    1995-01-01

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

  14. Tumor-Induced CD8+ T-Cell Dysfunction in Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Heriberto Prado-Garcia

    2012-01-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide and one of the most common types of cancers. The limited success of chemotherapy and radiotherapy regimes have highlighted the need to develop new therapies like antitumor immunotherapy. CD8+ T-cells represent a major arm of the cell-mediated anti-tumor response and a promising target for developing T-cell-based immunotherapies against lung cancer. Lung tumors, however, have been considered to possess poor immunogenicity; even so, lung tumor-specific CD8+ T-cell clones can be established that possess cytotoxicity against autologous tumor cells. This paper will focus on the alterations induced in CD8+ T-cells by lung cancer. Although memory CD8+ T-cells infiltrate lung tumors, in both tumor-infiltrating lymphocytes (TILs and malignant pleural effusions, these cells are dysfunctional and the effector subset is reduced. We propose that chronic presence of lung tumors induces dysfunctions in CD8+ T-cells and sensitizes them to activation-induced cell death, which may be associated with the poor clinical responses observed in immunotherapeutic trials. Getting a deeper knowledge of the evasion mechanisms lung cancer induce in CD8+ T-cells should lead to further understanding of lung cancer biology, overcome tumor evasion mechanisms, and design improved immunotherapeutic treatments for lung cancer.

  15. 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.

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

    OpenAIRE

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation...... abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion...... and ventilation to the transplanted lung of patients with and without a primary diagnosis of fibrosis did not differ significantly from each other. We conclude that PGD defined at 72 h does not lead to recognizable changes in ventilation-perfusion scintigrapy at 3 months, and scintigraphic findings do...

  19. 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.

  20. 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.

  1. Hashimoto’s Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion

    OpenAIRE

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo

    2013-01-01

    Hashimoto’s encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto’s encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto’s encephalopathy is very rare. We report a 65-year-old man wh...

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

    Directory of Open Access Journals (Sweden)

    Tsuboko Y

    2012-10-01

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

  3. Comparison between primary angioplasty and thrombolytic therapy on erectile dysfunction after acute ST elevation myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Ramazan Akdemir; Ekrem Yeter; (O)zlem Karakurt; Salih Orcan; Nihat Karakoyunlu; Mustafa Mucahit Balci; Levent Sa(g)nak; Hamit Ersoy; Mehmet Bulent Vatan; Harun Kilic

    2012-01-01

    Acute ST elevation myocarclial infarction has high mortality and morbidity rates.The majority of patients with this condition face erectile dysfunction in addition to other health problems,In this study,we aimed to investigate the effects of two different reperfusion strategies,primary angioplasty and thrombolytic therapy,on the prevalence of erectile dysfunction after acute myocardial infarction.Of the 71 patients matching the selection criteria,45 were treated with primary coronary angioplasty with stenting,and 26 were treated with thrombolytic agents.Erectile function was evaluated using the International Index of Erectile Function in the hospital to characterize each patient's sexual function before the acute myocardial infarction and 6 months after the event.The time required to restore blood flow to the artery affected by the infarct was found to be associated with the occurrence of erectile dysfunction after acute myocardial infarction.The increase in the prevalence of erectile dysfunction after acute myocardial infarction was 44.4% in the angioplasty group and 76.9% in the thrombolytic therapy group (P=0.008).In conclusion,this study has shown that reducing the time of reperfusion decreases the erectile dysfunction prevalence,and primary angioplasty is superior to thrombolytic therapy for decreasing the prevalence of erectile dysfunction after acute myocardial infarction.

  4. Impact of cytokine expression in the pre-implanted donor lung on the development of chronic lung allograft dysfunction subtypes.

    Science.gov (United States)

    Saito, T; Takahashi, H; Kaneda, H; Binnie, M; Azad, S; Sato, M; Waddell, T K; Cypel, M; Liu, M; Keshavjee, S

    2013-12-01

    The long-term success of lung transplantation continues to be challenged by the development of chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the relationship between cytokine expression levels in pre-implanted donor lungs and the posttransplant development of CLAD and its subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Of 109 patients who underwent bilateral lung or heart-lung transplantation and survived for more than 3 months, 50 BOS, 21 RAS and 38 patients with No CLAD were identified by pulmonary function test results. Using donor lung tissue biopsies sampled from each patient, expression levels of IL-6, IL-1β, IL-8, IL-10, interferon-γ and tumor necrosis factor-α mRNA were measured. IL-6 expression levels were significantly higher in pre-implanted lungs of patients that ultimately developed BOS compared to RAS and No CLAD (p = 0.025 and 0.011, respectively). Cox regression analysis demonstrated an association between high IL-6 expression levels and BOS development (hazard ratio = 4.98; 95% confidence interval = 2.42-10.2, p < 0.001). In conclusion, high IL-6 mRNA expression levels in pre-implanted donor lungs were associated with the development of BOS, not RAS. This association further supports the contention that early graft injury impacts on both late graft function and early graft function. PMID:24164971

  5. CD36 and Fyn kinase mediate malaria-induced lung endothelial barrier dysfunction in mice infected with Plasmodium berghei.

    Directory of Open Access Journals (Sweden)

    Ifeanyi U Anidi

    Full Text Available Severe malaria can trigger acute lung injury characterized by pulmonary edema resulting from increased endothelial permeability. However, the mechanism through which lung fluid conductance is altered during malaria remains unclear. To define the role that the scavenger receptor CD36 may play in mediating this response, C57BL/6J (WT and CD36-/- mice were infected with P. berghei ANKA and monitored for changes in pulmonary endothelial barrier function employing an isolated perfused lung system. WT lungs demonstrated a >10-fold increase in two measures of paracellular fluid conductance and a decrease in the albumin reflection coefficient (σalb compared to control lungs indicating a loss of barrier function. In contrast, malaria-infected CD36-/- mice had near normal fluid conductance but a similar reduction in σalb. In WT mice, lung sequestered iRBCs demonstrated production of reactive oxygen species (ROS. To determine whether knockout of CD36 could protect against ROS-induced endothelial barrier dysfunction, mouse lung microvascular endothelial monolayers (MLMVEC from WT and CD36-/- mice were exposed to H2O2. Unlike WT monolayers, which showed dose-dependent decreases in transendothelial electrical resistance (TER from H2O2 indicating loss of barrier function, CD36-/- MLMVEC demonstrated dose-dependent increases in TER. The differences between responses in WT and CD36-/- endothelial cells correlated with important differences in the intracellular compartmentalization of the CD36-associated Fyn kinase. Malaria infection increased total lung Fyn levels in CD36-/- lungs compared to WT, but this increase was due to elevated production of the inactive form of Fyn further suggesting a dysregulation of Fyn-mediated signaling. The importance of Fyn in CD36-dependent endothelial signaling was confirmed using in vitro Fyn knockdown as well as Fyn-/- mice, which were also protected from H2O2- and malaria-induced lung endothelial leak, respectively. Our

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

    OpenAIRE

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

    1995-01-01

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

  7. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    International Nuclear Information System (INIS)

    Acute Cl2 exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl2 inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl2 dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl2 exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO3− or NO2−. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl2 exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl2 inhalation. - Highlights: • Effect of 60 ppm*hr Cl2 gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor. • Alterations in surfactant homeostasis and pulmonary mechanics

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

    Science.gov (United States)

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F; Nielsen, Michael B; Mortensen, Jann

    2012-06-01

    Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found no significant correlation between lung function distribution at 3 months and PGD at 72 h. There was also no significant correlation between PGD scores at 72 h and lung function at 6 and 12 months. The same applied to scintigraphic scores for heterogeneity at 3 months compared with lung function at 6 and 12 months. Fifty-five percent of all patients had decreased ventilation function measured in the period from 6 to 12 months. Forty-nine percent of the patients had normal perfusion evaluations, and 51% had abnormal perfusion evaluations at 3 months. For ventilation evaluations, 72% were normal and 28% were abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion and ventilation to the transplanted lung of patients with and without a primary diagnosis of fibrosis did not differ significantly from each other. We conclude that PGD

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

    OpenAIRE

    Xiang, Meng; Fan, Jie

    2009-01-01

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

  10. 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

  11. 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

  12. Doppler Ultrasound in Chronic Renal Allograft Dysfunction : Can Acute Rejection be Predicted

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Kyung; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Ki Whang; Park, Ki Ill; Chung, Hyun Joo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1995-12-15

    To investigate Doppler sonographic findings valuable for detecting acute rejection in transplanted kidney with chronic allograft dysfunction. Forty-three renal allografts who underwent renal Doppler sonography and renal biopsy due to chronic allograft dysfunction were included. According to histopathologic findings, patients were classified into 2 groups: chronic component only(group 1, n=30) and acute rejection with or without chronic component 2 groups were performed. No definite difference in radio of renal size, cortical echogenecity, corticomedullary differentiation was noted between group 1 and group 2.Resistive index was 0.61{+-}0.18 in group 1 and 0.64{+-}0.22 in group 2, which showed no statistically significant difference. Characteristic Doppler sonographic findings suggesting acute rejection in cases of chronic allograft dysfunction were not found inauther's study. Therefore, minimal invasive renal biopsy to determine histopathologic status of transplanted kidney is essential in evaluation of the chronic allograft dysfunction

  13. 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...

  14. Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease

    Directory of Open Access Journals (Sweden)

    Amirmasoud Zangiabadi

    2014-01-01

    Full Text Available Group 3 pulmonary hypertension (PH is a common complication of chronic lung disease (CLD, including chronic obstructive pulmonary disease (COPD, interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  16. 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,

  17. Sildenafil and diastolic dysfunction after acute myocardial infarction trial

    DEFF Research Database (Denmark)

    Andersen, Mads J; Gustafsson, Finn; Hassager, Christian;

    2013-01-01

    Diastolic dysfunction following myocardial infarction is an important predictor of outcome, irrespective of left ventricular systolic function. Previous studies suggest that phosphordiesterase-5 inhibition has a favorable effect on the myocardium as well as on the pulmonary and systemic vasculature....

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

    OpenAIRE

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

    2011-01-01

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

  19. Preoperative Cardiac Variables of Diastolic Dysfunction and Clinical Outcomes in Lung Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Ajay Yadlapati

    2013-01-01

    Full Text Available Background. Orthotopic lung transplantation is now widely performed in patients with advanced lung disease. Patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation; however, there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function and elevated pretransplant pulmonary pressures. Methods. We reviewed the characteristics of 111 patients who underwent bilateral and unilateral lung transplants from 200 to 2009 in order to evaluate the prognostic significance of preoperative markers of diastolic function, including invasively measured pulmonary capillary wedge pressure (PCWP and echocardiographic variables of diastolic dysfunction including mitral A>E and A′>E′. Results. Out of 111 patients, 62 were male (56% and average age was 54.0 ± 10.5 years. Traditional echocardiographic Doppler variables of abnormal diastolic function, including A′>E′ and A>E, did not predict adverse events (P=0.49. Mildly elevated pretransplant PCWP (16–20 mmHg and moderately/severely elevated PCWP (>20 mmHg were not associated with adverse clinical events after transplant (P=0.30. Additionally, all clinical endpoints did not show any statistical significance between the two groups. Conclusions. Pre-lung transplant invasive and echocardiographic findings of elevated pulmonary pressures and abnormal left ventricular diastolic function are not predictive of adverse posttransplant clinical events.

  20. 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

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

    OpenAIRE

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

    2008-01-01

    Abstract Introduction Independent lung ventilation is a form of protective ventilation strategy used in adult asymmetric acute lung injury, where the application of conventional mechanical ventilation can produce ventilator-induced lung injury and ventilation-perfusion mismatch. Only a few experiences have been published on the use of independent lung ventilation in newborn patients. Case presentation We present a case of independent lung ventilation in a 16-day-old infant of 3.5 kg body weig...

  2. Acute Aortic Dissection Extending Into the Lung.

    Science.gov (United States)

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

    2015-07-01

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

  3. SURFACTANT DYSFUNCTION IN LUNG CONTUSION WITH AND WITHOUT SUPERIMPOSED GASTRIC ASPIRATION IN A RAT MODEL

    OpenAIRE

    Raghavendran, Krishnan; Davidson, Bruce A.; Paul R. Knight; Wang, Zhengdong; Helinski, Jadwiga; Chess, Patricia R.; Notter, Robert H.

    2008-01-01

    This study investigates surfactant dysfunction in rats with lung contusion (LC) induced by blunt chest trauma. Rats at 24 h postcontusion had a decreased percent content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL) and altered large-aggregate composition with decreased phosphatidylcholine (PC), increased lyso-PC, and increased protein compared with uninjured controls. The surface activity of large aggregates on a pulsating bubble surfactometer was also severely imp...

  4. Phospholipase D signaling mediates reactive oxygen species-induced lung endothelial barrier dysfunction.

    Science.gov (United States)

    Usatyuk, Peter V; Kotha, Sainath R; Parinandi, Narasimham L; Natarajan, Viswanathan

    2013-01-01

    Reactive oxygen species (ROS) have emerged as critical players in the pathophysiology of pulmonary disorders and diseases. Earlier, we have demonstrated that ROS stimulate lung endothelial cell (EC) phospholipase D (PLD) that generates phosphatidic acid (PA), a second messenger involved in signal transduction. In the current study, we investigated the role of PLD signaling in the ROS-induced lung vascular EC barrier dysfunction. Our results demonstrated that hydrogen peroxide (H2O2), a typical physiological ROS, induced PLD activation and altered the barrier function in bovine pulmonary artery ECs (BPAECs). 1-Butanol, the quencher of PLD, generated PA leading to the formation of physiologically inactive phosphatidyl butanol but not its biologically inactive analog, 2-butanol, blocked the H2O2-mediated barrier dysfunction. Furthermore, cell permeable C2 ceramide, an inhibitor of PLD but not the C2 dihydroceramide, attenuated the H2O2-induced PLD activation and enhancement of paracellular permeability of Evans blue conjugated albumin across the BPAEC monolayers. In addition, transfection of BPAECs with adenoviral constructs of hPLD1 and mPLD2 mutants attenuated the H2O2-induced barrier dysfunction, cytoskeletal reorganization and distribution of focal adhesion proteins. For the first time, this study demonstrated that the PLD-generated intracellular bioactive lipid signal mediator, PA, played a critical role in the ROS-induced barrier dysfunction in lung vascular ECs. This study also underscores the importance of PLD signaling in vascular leak and associated tissue injury in the etiology of lung diseases among critically ill patients encountering oxygen toxicity and excess ROS production during ventilator-assisted breathing.

  5. Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD)

    OpenAIRE

    McFetridge, Lynne; McMorrow, Aoife; Morrison, Patrick J.; Shields, Michael D.

    2009-01-01

    Surfactant deficiency and the resultant respiratory distress syndrome (RDS) seen in preterm infants is a major cause of respiratory morbidity in this population. Until recently, the contribution of surfactant to respiratory morbidity in infancy was limited to the neonatal period. It is now recognised that inborn errors of surfactant metabolism leading to surfactant dysfunction account for around 10% of childhood interstitial lung disease (chILD). These abnormalities can be detected by blood s...

  6. Dysfunctional lung anatomy and small airways degeneration in COPD

    Directory of Open Access Journals (Sweden)

    Burgel PR

    2013-01-01

    Full Text Available Clémence Martin, Justine Frija, Pierre-Régis BurgelDepartment of Respiratory Medicine, Cochin Hospital, AP-HP and Université Paris Descartes, Sorbonne Paris Cité, Paris, FranceAbstract: Chronic obstructive pulmonary disease (COPD is characterized by incompletely reversible airflow obstruction. Direct measurement of airways resistance using invasive techniques has revealed that the site of obstruction is located in the small conducting airways, ie, bronchioles with a diameter < 2 mm. Anatomical changes in these airways include structural abnormalities of the conducting airways (eg, peribronchiolar fibrosis, mucus plugging and loss of alveolar attachments due to emphysema, which result in destabilization of these airways related to reduced elastic recoil. The relative contribution of structural abnormalities in small conducting airways and emphysema has been a matter of much debate. The present article reviews anatomical changes and inflammatory mechanisms in small conducting airways and in the adjacent lung parenchyma, with a special focus on recent anatomical and imaging data suggesting that the initial event takes place in the small conducting airways and results in a dramatic reduction in the number of airways, together with a reduction in the cross-sectional area of remaining airways. Implications of these findings for the development of novel therapies are briefly discussed.Keywords: emphysema, small airways disease, airway mucus, innate immunity, adaptive immunity

  7. Lung function evaluation in acute postradiation pneumonitis

    International Nuclear Information System (INIS)

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

  8. 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.

  9. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    lung injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized......BACKGROUND: Surfactant protein D (SP-D) is a collection that plays important roles in modulating host defense functions and maintaining phospholipid homeostasis in the lung. The aim of current study was to characterize comparatively the SP-D response in bronchoalveolar lavage (BAL) and serum in...... three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP-D in...

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

    OpenAIRE

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

    2014-01-01

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

  12. Sphincter of Oddi dysfunction and bile duct microlithiasis in acute idiopathic pancreatitis

    OpenAIRE

    Elta, Grace H.

    2008-01-01

    Although there are numerous causes of acute pancreatitis, an etiology cannot always be found. Two potential etiologies, microlithiasis and sphincter of Oddi dysfunction, are discussed in this review. Gallbladder microlithiasis, missed on transcutaneous ultrasound, is reported as the cause of idiopathic acute pancreatitis in a wide frequency range of 6%-80%. The best diagnostic technique for gallbladder microlithiasis is endoscopic ultrasound although biliary crystal analysis and empiric chole...

  13. Strategies to improve oxygenation in experimental acute lung injury

    OpenAIRE

    Hartog, Arthur

    2000-01-01

    textabstractOne of the most important clinical syndromes, in which failure of oxygen uptake in the lung leads to severe hypoxia, is the so-called acute respiratory distress syndrome (ARDS). ARDS is a complex of clinical signs and symptoms which occur following diverse pulmonary or systemic insults, including sepsis. shock, pneumonia. trauma, liquid aspiration. hematological disorders, smoke inhalation, and many others, In ARDS, the treatments available are still inadequate and morbidity, mort...

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

    Science.gov (United States)

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

    2010-08-01

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

  15. Improving documentation and coding for acute organ dysfunction biases estimates of changing sepsis severity and burden: a retrospective study

    OpenAIRE

    Rhee, Chanu; Murphy, Michael V.; Li, Lingling; Platt, Richard; Klompas, Michael; ,

    2015-01-01

    Introduction Claims-based analyses report that the incidence of sepsis-associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if so, whether this is biasing estimates of rising severe sepsis incidence and severity. Methods We assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hepat...

  16. Improving documentation and coding for acute organ dysfunction biases estimates of changing sepsis severity and burden: a retrospective study

    OpenAIRE

    Rhee, Chanu; Murphy, Michael V.; Li, Lingling; Platt, Richard; Klompas, Michael

    2015-01-01

    Introduction: Claims-based analyses report that the incidence of sepsis-associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if so, whether this is biasing estimates of rising severe sepsis incidence and severity. Methods: We assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hep...

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

    OpenAIRE

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

    2016-01-01

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

  18. Acute expanded perlite exposure with persistent reactive airway dysfunction syndrome.

    Science.gov (United States)

    Du, Chung-Li; Wang, Jung-Der; Chu, Po-Chin; Guo, Yue-Liang Leon

    2010-01-01

    Expanded perlite has been assumed as simple nuisance, however during an accidental spill out in Taiwan, among 24 exposed workers followed for more than 6 months, three developed persisted respiratory symptoms and positive provocation tests were compatible with reactive airway dysfunction syndrome. During simulation experiment expanded perlite is shown to be very dusty and greatly exceed current exposure permission level. Review of literature and evidence, though exposure of expanded perlite below permission level may be generally safe, precautionary protection of short term heavy exposure is warranted.

  19. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Massa, Christopher B.; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L.; Gow, Andrew J., E-mail: Gow@rci.rutgers.edu

    2014-07-01

    Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor.

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

    Science.gov (United States)

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

    2016-06-01

    Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD), which is characterized by airway remodeling, lung inflammation and fibrosis, emphysema, and respiratory failure. The current therapies can improve COPD management but cannot arrest its progression and reduce mortality. Hence, there is a major interest in identifying molecules susceptible of development into new drugs to prevent or reduce CS-induced lung injury. Serelaxin (RLX), or recombinant human relaxin-2, is a promising candidate because of its anti-inflammatory and antifibrotic properties highlighted in lung disease models. Here, we used a guinea pig model of CS-induced lung inflammation, and remodeling reproducing some of the hallmarks of COPD. Animals exposed chronically to CS (8 weeks) were treated with vehicle or RLX, delivered by osmotic pumps (1 or 10 μg/day) or aerosol (10 μg/ml/day) during CS treatment. Controls were nonsmoking animals. RLX maintained airway compliance to a control-like pattern, likely because of its capability to counteract lung inflammation and bronchial remodeling. In fact, treatment of CS-exposed animals with RLX reduced the inflammatory recruitment of leukocytes, accompanied by a significant reduction of the release of proinflammatory cytokines (tumor necrosis factor α and interleukin-1β). Moreover, RLX was able to counteract the adverse bronchial remodeling and emphysema induced by CS exposure by reducing goblet cell hyperplasia, smooth muscle thickening, and fibrosis. Of note, RLX delivered by aerosol has shown a comparable efficacy to systemic administration in reducing CS-induced lung dysfunction and damage. In conclusion, RLX emerges as a new molecule to counteract CS-induced inflammatory lung diseases. PMID:27048661

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

    OpenAIRE

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

    2011-01-01

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

  2. CD4+ T Lymphocytes are Not Necessary for the Acute Rejection of Vascularized Mouse Lung Transplants

    OpenAIRE

    Gelman, Andrew E.; Okazaki, Mikio; Lai, Jiaming; Kornfeld, Christopher G.; Kreisel, Friederike H.; Richardson, Steven B.; Sugimoto, Seiichiro; Tietjens, Jeremy R.; Patterson, G. Alexander; Krupnick, Alexander S.; Kreisel, Daniel

    2008-01-01

    Acute rejection continues to present a major obstacle to successful lung transplantation. While CD4+ T lymphocytes are critical for the rejection of some solid organ grafts the role of CD4+ T cells in the rejection of lung allografts is largely unknown. In this study we demonstrate in a novel model of orthotopic vascularized mouse lung transplantation that acute rejection of lung allografts is independent of CD4+ T cell-mediated allorecognition pathways. CD4+ T cell-independent rejection occu...

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

    OpenAIRE

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2009-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-04-01

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

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

    International Nuclear Information System (INIS)

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

  7. Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity?

    Science.gov (United States)

    Tanriverdi, F; De Bellis, A; Teksahin, H; Alp, E; Bizzarro, A; Sinisi, A A; Bellastella, G; Paglionico, V A; Bellastella, A; Unluhizarci, K; Doganay, M; Kelestimur, F

    2012-12-01

    Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months

  8. 中医辨证治疗急性肺损伤/急性呼吸窘迫综合征机械通气患者胃肠功能障碍的临床研究%The clinical effect of traditional Chinese medicine dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury/acute respiratory distress syndrome undergoing mechanical ventilation

    Institute of Scientific and Technical Information of China (English)

    王宏飞; 王勇强; 李寅; 高红梅; 陈洁; 伊学军; 常文秀

    2014-01-01

    Objective To explore the clinical effect of traditional Chinese medicine (TCM) dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury / acute respiratory distress syndrome(ALI/ARDS)undergoing mechanical ventilation. Methods A prospective,randomized controlled trial was conducted. Ninety-six ALI/ARDS patients admitted in intensive care unit(ICU)and treated with mechanical ventilation in Tianjin First Central Hospital were chosen and randomly divided into traditional Chinese medicine(TCM) group and conventional therapy group using a random number table,48 patients in each group. Conventional therapy alone was used in conventional therapy group,and TCM therapy of primarily using Dachengqi decoction combined with conventional therapy was applied in TCM group〔Dachengqi decoction was composed of mongolian milkvetch root 15 g, pilose asiabell toot 15 g,Chinese angelica 10 g,officinal magnolia bark 10 g,tangerine peel 10 g,immature tangerine fruit 10 g,peach seed 10 g,white peony root 12 g,red peony root 12 g,immature bitter orange 6 g,mongolian dandelion herb 30 g,radish seed(stir-fried)30 g,foxtail millet sprout 20 g,barley sprout 20 g,glauber salt 9 g (with water),rhubarb 10 g(added in water at last)〕,one dose orally taken daily for 28 days. The intra-abdominal pressure(IAP),gastrointestinal diseases in TCM symptom score and the incidence of gastrointestinal dysfunction were compared between the two groups before treatment and on the 3rd,6th and 8th day after treatment. Results There were no statistical significant differences in IAP and TCM symptom scores between the two groups before treatment (both P>0.05),but after treatment with the prolongation of therapeutic time the IAP and TCM symptom scores were decreased gradually compared with those before treatment,having reached the valley value on the 18th day and the changes in TCM group were more remarkable〔IAP(mmHg,1 mmHg=0.133 kPa):0.91±0.69 vs. 2.08±0.92, TCM

  9. Managing bronchiolitis obliterans syndrome (BOS) and chronic lung allograft dysfunction (CLAD) in children: what does the future hold?

    Science.gov (United States)

    Snell, Gregory I; Paraskeva, Miranda; Westall, Glen P

    2013-08-01

    The success of pediatric lung transplantation continues to be limited by long-term graft dysfunction. Historically this has been characterized as an obstructive spirometric defect in the form of the bronchiolitis obliterans syndrome (BOS). It is recognized, however, that this does not reflect many of the other acknowledged etiologies of chronic lung dysfunction-noting it is the sum of the parts that contribute to respiratory morbidity and mortality after transplant. The term chronic lung allograft dysfunction (CLAD) has been coined to reflect these other entities and, in particular, a group of relatively recently described lung disorders called the restrictive allograft syndrome (RAS). RAS is characterized by a restrictive spirometric defect. Although these entities have not yet been studied in a pediatric setting their association with poor compliance, antibody-mediated rejection (AMR), and post-infectious lung damage (particularly viral) warrants attention by pediatric lung transplant teams. Current therapy for the BOS subset of CLAD is otherwise limited to changing immunosuppressants and avoiding excessive infectious risk by avoiding over-immunosuppression. Long-term macrolide therapy in lung transplantation is not of proven efficacy. Reviewing previous BOS studies to explore restrictive spirometric cases and joint projects via groups like the International Pediatric Lung Transplant Collaborative will be the way forward to solve this pressing problem.

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

    Institute of Scientific and Technical Information of China (English)

    唐光华

    2003-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  12. Surfactant dysfunction and lung inflammation in the female mouse model of lymphangioleiomyomatosis.

    Science.gov (United States)

    Atochina-Vasserman, Elena N; Guo, Chang-Jiang; Abramova, Elena; Golden, Thea N; Sims, Michael; James, Melane L; Beers, Michael F; Gow, Andrew J; Krymskaya, Vera P

    2015-07-01

    Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations of the tumor suppressor genes, tuberous sclerosis complex (TSC) 1 or TSC2. LAM affects women almost exclusively, and it is characterized by neoplastic growth of atypical smooth muscle-like TSC2-null LAM cells in the pulmonary interstitium, cystic destruction of lung parenchyma, and progressive decline in lung function. In this study, we hypothesized that TSC2-null lesions promote a proinflammatory environment, which contributes to lung parenchyma destruction. Using a TSC2-null female murine LAM model, we demonstrate that TSC2-null lesions promote alveolar macrophage accumulation, recruitment of immature multinucleated cells, an increased induction of proinflammatory genes, nitric oxide (NO) synthase 2, IL-6, chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein 1 (MCP1), chemokine (C-X-C motif) ligand 1 (CXCL1)/keratinocyte chemoattractant (KC), and up-regulation of IL-6, KC, MCP-1, and transforming growth factor-β1 levels in bronchoalveolar lavage fluid. Bronchoalveolar lavage fluid also contained an increased level of surfactant protein (SP)-D, but not SP-A, significant reduction of SP-B levels, and a resultant increase in alveolar surface tension. Consistent with the growth of TSC2-null lesions, NO levels were also increased and, in turn, modified SP-D through S-nitrosylation, forming S-nitrosylated SP-D, a known consequence of lung inflammation. Progressive growth of TSC2-null lesions was accompanied by elevated levels of matrix metalloproteinase-3 and -9. This report demonstrates a link between growth of TSC2-null lesions and inflammation-induced surfactant dysfunction that might contribute to lung destruction in LAM. PMID:25474372

  13. Therapeutic Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Models of Pulmonary and Extrapulmonary Acute Lung Injury.

    Science.gov (United States)

    Liu, Ling; He, Hongli; Liu, Airan; Xu, Jingyuan; Han, Jibin; Chen, Qihong; Hu, Shuling; Xu, Xiuping; Huang, Yingzi; Guo, Fengmei; Yang, Yi; Qiu, Haibo

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (MSCs) offer a promising therapy for acute lung injury (ALI). However, whether the same MSC treatments possess similar potential for different ALI models is not fully clear. The present study evaluated the distribution and therapeutic effects of intravenous MSC administration for the treatment of intratracheal lipopolysaccharide (LPS)-induced intrapulmonary ALI and intravenous LPS/zymosan-induced extrapulmonary ALI, matched with lung injury severity, at 30 min and 1, 3, and 7 days. We found that MSC transplantation attenuated lung injury and inhibited lung inflammation in both ALI models. The benefits of MSCs were more significant in the intrapulmonary ALI mice. In vivo and ex vivo fluorescence imaging showed that MSCs primarily homed into the lung. However, more MSCs were recruited into the lungs of the intrapulmonary ALI mice than those of the extrapulmonary ALI mice over the time course. A few MSCs were also detected in the liver and spleen at days 3 and 7. In addition, the two ALI models showed different extrapulmonary organ dysfunction. A lower percentage of cell apoptosis and SDF-1α levels was found in the liver and spleen of the intrapulmonary ALI mice than in those of the extrapulmonary ALI mice. These results suggested that the two ALI models were accompanied with different degrees of extrapulmonary organ damage, which resulted in differences in the trafficking and accumulation of MSCs to the injured lung and consequently accounted for different therapeutic effects of MSCs for lung repair in the two ALI models. These data suggest that intravenous administration of MSCs has a greater potential for the treatment of intrapulmonary ALI than extrapulmonary ALI matched with lung injury severity; these differences were due to more recruitment of MSCs in the lungs of intrapulmonary ALI mice than those of extrapulmonary ALI mice. This finding may contribute to the clinical use of MSCs for the treatment of ALI. PMID

  14. Sphincter of Oddi dysfunction and bile duct microlithiasis in acute idiopathic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Grace H Elta

    2008-01-01

    Although there are numerous causes of acute pancreatitis,an etiology cannot always be found.Two potential etiologies,microlithiasis and sphincter of Oddi dysfunction,are discussed in this review.Gallbladder microlithiasis,missed on transcutaneous ultrasound,is reported as the cause of idiopathic acute pancreatitis in a wide frequency range of 6%-80%.The best diagnostic technique for gallbladder microlithiasis is endoscopic ultrasound although biliary crystal analysis and empiric cholecystectomy remain as reasonable options.In contrast,in patients who are post-cholecystectomy,bile duct microlithiasis does not appear to have a role in the pathogenesis of acute pancreatitis.Sphincter of Oddi dysfunction is present in 30%-65% of patientswith idiopathic acute recurrent pancreatitis in whom other diagnoses have been excluded.It is unclear if this sphincter dysfunction was the original etiology of the first episode of pancreatitis although it appears to have a causative role in recurring episodes since sphincter ablation decreases the frequency of recurrent attacks.Unfortunately,this conclusion is primarily based on small retrospective case series;larger prospective studies of the outcome of pancreatic sphincterotomy for SOD-associated acute pancreatitis are sorely needed.Another problem with this diagnosis and its treatment is the concern over potential procedure related complications from endoscopic retrograde cholangiopancreatography (ERCP),manometry and pancreatic sphincterotomy.For these reasons,patients should have recurrent acute pancreatitis,not a single episode,and have a careful informed consent before assessment of the sphincter of Oddi is undertaken.

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

    Science.gov (United States)

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

    2016-02-01

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

  16. Surfactant dysfunction during overexpression of TGF-β1 precedes profibrotic lung remodeling in vivo.

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Boden, Caroline; Echaide, Mercedes; Perez-Gil, Jesus; Kolb, Martin; Gauldie, Jack; Maus, Ulrich A; Ochs, Matthias; Knudsen, Lars

    2016-06-01

    Transforming growth factor-β1 (TGF-β1) is involved in regulation of cellular proliferation, differentiation, and fibrogenesis, inducing myofibroblast migration and increasing extracellular matrix synthesis. Here, TGF-β1 effects on pulmonary structure and function were analyzed. Adenovirus-mediated gene transfer of TGF-β1 in mice lungs was performed and evaluated by design-based stereology, invasive pulmonary function testing, and detailed analyses of the surfactant system 1 and 2 wk after gene transfer. After 1 wk decreased static compliance was linked with a dramatic alveolar derecruitment without edema formation or increase in the volume of septal wall tissue or collagen fibrils. Abnormally high surface tension correlated with downregulation of surfactant proteins B and C. TTF-1 expression was reduced, and, using PLA (proximity ligand assay) technology, we found Smad3 and TTF-1 forming complexes in vivo, which are normally translocated into the nucleus of the alveolar epithelial type II cells (AE2C) but in the presence of TGF-β1 remain in the cytoplasm. AE2C show altered morphology, resulting in loss of total apical surface area per lung and polarity. These changes of AE2C were progressive 2 wk after gene transfer and correlated with lung compliance. Although static lung compliance remained low, the volume of septal wall tissue and collagen fibrils increased 2 wk after gene transfer. In this animal model, the primary effect of TGF-β1 signaling in the lung is downregulation of surfactant proteins, high surface tension, alveolar derecruitment, and mechanical stress, which precede fibrotic tissue remodeling and progressive loss of AE2C polarity. Initial TTF-1 dysfunction is potentially linked to downregulation of surfactant proteins. PMID:27106287

  17. 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. PMID:25008149

  18. 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.

  19. Anaemia is an independent predictor of mortality in patients with left ventricular systolic dysfunction following acute myocardial infarction

    DEFF Research Database (Denmark)

    Valeur, Nana; Nielsen, Olav Wendelboe; McMurray, John J V;

    2006-01-01

    BACKGROUND: In patients with chronic heart failure (HF), mortality is inversely related to haemoglobin (hgb) concentration. We investigated the prognostic importance of anaemia in patients with acute myocardial infarction (AMI) and left ventricular systolic dysfunction (LVSD) with and without HF...

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

    OpenAIRE

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

    2010-01-01

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

  1. Percutaneous coronary intervention for acute myocardial infarction in elderly patients with renal dysfunction: results from the Korea Acute Myocardial Infarction Registry.

    Science.gov (United States)

    Lim, Sang Yup; Bae, Eun Hui; Choi, Joon Seok; Kim, Chang Seong; Ma, Seong Kwon; Ahn, Youngkeun; Jeong, Myung Ho; Kim, Weon; Woo, Jong Shin; Kim, Young Jo; Cho, Myeong Chan; Kim, Chong Jin; Kim, Soo Wan

    2013-07-01

    This study aimed to evaluate the effects of percutaneous coronary intervention (PCI) on short- and long-term major adverse cardiac events (MACE) in elderly (>75 yr old) acute myocardial infarction (AMI) patients with renal dysfunction. As part of Korea AMI Registry (KAMIR), elderly patients with AMI and renal dysfunction (GFRrenal dysfunction, PCI therapy yields favorable in-hospital and short-term and long-term MACE-free survival.

  2. Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung.

    Science.gov (United States)

    Zhang, Xuefeng; Jiang, Susan; Yu, Jinlong; Kuzontkoski, Paula M; Groopman, Jerome E

    2015-08-01

    Pulmonary complications are common in both AIDS patients and cocaine users. We addressed the cellular and molecular mechanisms by which HIV and cocaine may partner to induce their deleterious effects. Using primary lung lymphatic endothelial cells (L-LECs), we examined how cocaine and HIV-1 gp120, alone and together, modulate signaling and functional properties of L-LECs. We found that brief cocaine exposure activated paxillin and induced cytoskeletal rearrangement, while sustained exposure increased fibronectin (FN) expression, decreased Robo4 expression, and enhanced the permeability of L-LEC monolayers. Moreover, incubating L-LECs with both cocaine and HIV-1 gp120 exacerbated hyperpermeability, significantly enhanced apoptosis, and further impaired in vitro wound healing as compared with cocaine alone. Our studies also suggested that the sigma-1 receptor (Sigma-1R) and the dopamine-4 receptor (D4R) are involved in cocaine-induced pathology in L-LECs. Seeking clinical correlation, we found that FN levels in sera and lung tissue of HIV(+) donors were significantly elevated as compared to HIV(-) donors. Our in vitro data demonstrate that cocaine and HIV-1 gp120 induce dysfunction and damage of lung lymphatics, and suggest that cocaine use may exacerbate pulmonary edema and fibrosis associated with HIV infection. Continued exploration of the interplay between cocaine and HIV should assist the design of therapeutics to ameliorate HIV-induced pulmonary disorders within the drug using population. PMID:26311830

  3. Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients

    NARCIS (Netherlands)

    Morandi, A; Pandharipande, P; Trabucchi, M; Rozzini, R; Mistraletti, G; Trompeo, A C; Gregoretti, C; Gattinoni, L; Ranieri, M V; Brochard, L; Annane, D; Putensen, C; Guenther, U; Fuentes, P; Tobar, E; Anzueto, A R; Esteban, A; Skrobik, Y; Salluh, J I F; Soares, M; Granja, C; Stubhaug, A; de Rooij, S E; Ely, E Wesley

    2008-01-01

    BACKGROUND: Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium

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

    OpenAIRE

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

    2008-01-01

    The pentraxin 3 (PTX3) is an acute phase proinflammatory protein produced by fibroblasts and alveolar epithelial cells. We have previously demonstrated that PTX3 is a key modulator of inflammation. Mechanical ventilation (MV) is a life saving therapeutic approach for patients with acute lung injury that, nevertheless could lead to an inflammatory response and tissue injury (ventilator-induced lung injury: VILI), representing a major cause of iatrogenic lung damage in intensive units. Our obje...

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

    OpenAIRE

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

    2003-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    OpenAIRE

    Luh, Shi-Ping; Chiang, Chi-huei

    2006-01-01

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

  8. 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

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

    OpenAIRE

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

    1999-01-01

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

  10. Distinct expression patterns of alveolar "alarmins" in subtypes of chronic lung allograft dysfunction.

    Science.gov (United States)

    Saito, T; Liu, M; Binnie, M; Sato, M; Hwang, D; Azad, S; Machuca, T N; Zamel, R; Waddell, T K; Cypel, M; Keshavjee, S

    2014-06-01

    The long-term success of lung transplantation is limited by chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the alveolar alarmin profiles in CLAD subtypes, restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS). Bronchoalveolar lavage (BAL) samples were collected from 53 recipients who underwent double lung or heart-lung transplantation, including patients with RAS (n = 10), BOS (n = 18) and No CLAD (n = 25). Protein levels of alarmins such as S100A8, S100A9, S100A8/A9, S100A12, S100P, high-mobility group box 1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in BAL fluid were measured. RAS and BOS showed higher expressions of S100A8, S100A8/A9 and S100A12 compared with No CLAD (p < 0.0001, p < 0.0001, p < 0.0001 in RAS vs. No CLAD, p = 0.0006, p = 0.0044, p = 0.0086 in BOS vs. No CLAD, respectively). Moreover, RAS showed greater up-regulation of S100A9, S100A8/A9, S100A12, S100P and HMGB1 compared with BOS (p = 0.0094, p = 0.038, p = 0.041, p = 0.035 and p = 0.010, respectively). sRAGE did not show significant difference among the three groups (p = 0.174). Our results demonstrate distinct expression patterns of alveolar alarmins in RAS and BOS, suggesting that RAS and BOS may represent biologically different subtypes. Further refinements in biologic profiling will lead to a better understanding of CLAD. PMID:24787265

  11. Therapeutic modulation of coagulation and fibrinolysis in acute lung injury and the acute respiratory distress syndrome.

    Science.gov (United States)

    Sebag, Sara C; Bastarache, Julie A; Ware, Lorraine B

    2011-09-01

    Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by excessive intraalveolar fibrin deposition, driven, at least in part by inflammation. The imbalance between activation of coagulation and inhibition of fibrinolysis in patients with ALI/ARDS favors fibrin formation and appears to occur both systemically and in the lung and airspace. Tissue factor (TF), a key mediator of the activation of coagulation in the lung, has been implicated in the pathogenesis of ALI/ARDS. As such, there have been numerous investigations modulating TF activity in a variety of experimental systems in order to develop new therapeutic strategies for ALI/ARDS. This review will summarize current understanding of the role of TF and other proteins of the coagulation cascade as well the fibrinolysis pathway in the development of ALI/ARDS with an emphasis on the pathways that are potential therapeutic targets. These include the TF inhibitor pathway, the protein C pathway, antithrombin, heparin, and modulation of fibrinolysis through plasminogen activator- 1 (PAI-1) or plasminogen activators (PA). Although experimental studies show promising results, clinical trials to date have proven unsuccessful in improving patient outcomes. Modulation of coagulation and fibrinolysis has complex effects on both hemostasis and inflammatory pathways and further studies are needed to develop new treatment strategies for patients with ALI/ARDS. PMID:21401517

  12. Preferential killing of human lung cancer cell lines with mitochondrial dysfunction by nonthermal dielectric barrier discharge plasma

    OpenAIRE

    Panngom, K; Baik, K Y; Nam, M K; Han, J. H.; Rhim, H; Choi, E. H.

    2013-01-01

    The distinctive cellular and mitochondrial dysfunctions of two human lung cancer cell lines (H460 and HCC1588) from two human lung normal cell lines (MRC5 and L132) have been studied by dielectric barrier discharge (DBD) plasma treatment. This cytotoxicity is exposure time-dependent, which is strongly mediated by the large amount of H2O2 and NOx in culture media generated by DBD nonthermal plasma. It is found that the cell number of lung cancer cells has been reduced more than that of the lun...

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

    OpenAIRE

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

    1982-01-01

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

  14. 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

  15. 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

  16. Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome.

    Science.gov (United States)

    Glas, G J; Van Der Sluijs, K F; Schultz, M J; Hofstra, J-J H; Van Der Poll, T; Levi, M

    2013-01-01

    Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho-alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome (ARDS), pneumonia and ventilator-induced lung injury (VILI), and is important to the pathogenesis of these conditions. The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. There is an intense and bidirectional interaction between coagulation and inflammatory pathways in the bronchoalveolar compartment. Systemic or local administration of anticoagulant agents (including activated protein C, antithrombin and heparin) and profibrinolytic agents (such as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ARDS and pneumonia. PMID:23114008

  17. Saturated hydrogen saline attenuates endotoxin-induced acute liver dysfunction in rats.

    Science.gov (United States)

    Xu, X-F; Zhang, J

    2013-01-01

    To determine the effect of saturated hydrogen saline on lipopolysaccharide (LPS)-induced acute liver dysfunction, rats were divided into control, LPS, and LPS plus saturated hydrogen saline (LPS+H(2)) groups. Treatment with saturated hydrogen saline prolonged the median survival time and reduced liver dysfunction. Moreover, saturated hydrogen saline significantly reduced pathological alterations in liver tissues, the number of ballooned hepatocytes, serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, and myeloperoxidase (MPO) and malondialdehyde (MDA) levels in liver tissues (Phydrogen saline treatment. Saturated hydrogen saline also decreased phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated Jun kinase (p-JNK), nuclear factor-kappa B (NF-kappaB), and second mitochondria-derived activator of caspase (Smac) levels, and increased p38 activation (Phydrogen saline may attenuate LPS-induced acute liver dysfunction in rats, possibly by reducing inflammation and cell apoptosis. Mitogen-activated protein kinase (MAPK), NF-kappaB, and Smac may contribute to saturated hydrogen saline-mediated liver protection.

  18. Intra-Peritoneal Administration of Mitochondrial DNA Provokes Acute Lung Injury and Systemic Inflammation via Toll-Like Receptor 9.

    Science.gov (United States)

    Zhang, Lemeng; Deng, Songyun; Zhao, Shuangping; Ai, Yuhang; Zhang, Lina; Pan, Pinhua; Su, Xiaoli; Tan, Hongyi; Wu, Dongdong

    2016-01-01

    The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation. Following LPS injection, plasma mtDNA copies peak at 8 h. Compared with wild-type (WT) mice, mtDNA in toll like receptor 4 knockout (TLR4 KO) mice were significantly decreased. MtDNA intra-peritoneal administration causes apparent ALI as demonstrated by increased lung injury score, bronchoalveolar lavage fluid (BALF) total protein and wet/dry (W/D) ratio; mtDNA injection also directly provokes systemic inflammation, as demonstrated by increased IL-1β, IL-6, high-mobility group protein B1 (HMGB1) level; while nuclear DNA (nDNA) could not induce apparent ALI and systemic inflammation. However, compared with WT mice, TLR4 KO could not protect from mtDNA induced ALI and systemic inflammation. Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1β, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner. PMID:27589725

  19. Measuring dead-space in acute lung injury.

    Science.gov (United States)

    Kallet, R H

    2012-11-01

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

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

    Science.gov (United States)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-02-13

    Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies. PMID:26530889

  1. Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction.

    Science.gov (United States)

    Matos, Ana Cristina Carvalho de; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão Junior, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; Arruda, Érika Ferraz de; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

    2015-01-01

    Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID:26154553

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

    Science.gov (United States)

    Walz, M; Muhr, G

    1992-11-01

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

  3. Elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation.

    Directory of Open Access Journals (Sweden)

    Joshua M Diamond

    Full Text Available INTRODUCTION: Primary graft dysfunction (PGD is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD. METHODS: We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE. RESULTS: There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40% and 47 non-PGD subjects (59% received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF. Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03. The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02; there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD (p = 0.9. CONCLUSIONS: Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.

  4. 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

  5. EARLY ALLOGRAFT DYSFUNCTION AND ACUTE KIDNEY INJURY AFTER LIVER TRANSPLANTATION: DEFINITIONS, RISK FACTORS AND CLINICAL SIGNIFICANCE

    Directory of Open Access Journals (Sweden)

    L. Y. Moysyuk

    2012-01-01

    Full Text Available This review discusses issues related to intensive care in recipients of transplanted liver in the early postoperative period, with an emphasis on contemporary conditions and attitudes that are specific for this group of patients. Early allograft dysfunction (EAD requires immediate diagnosis and appropriate treatment in case. The causes of the EAD and therapeutic tactics are discussed. Acute kidney injury (AKI and renal failure are common in patients after transplantation. We consider etiology, risk factors, diagnosis and treatment guidelines for AKI. The negative impact of EAD and AKI on the grafts survival and recipients is demonstrated. 

  6. Evaluation of respiratory dysfunction in a pig model of severe acute dichlorvos poisoning

    Institute of Scientific and Technical Information of China (English)

    HE Xin-hua; WU Jun-yuan; LI Chun-sheng; SU Zhi-yu; JI Xian-fei; HAN Yi; WANG Sheng-qi; ZHANG Jian

    2012-01-01

    Background Respiratory failure is the main cause of death in acute organophosphorus pesticide poisoning.In this study,a pulse-induced contour cardiac output monitor was used to evaluate the respiratory status in a pig model of acute dichlorvos poisoning.Methods Twenty female pigs were randomly allocated to dichlorvos (n=7),atropine (n=7),and control (n=6) groups.In the dichlorvos group,pigs were administered 80% emulsifiable dichlorvos (100 mg/kg) via a gastric tube.In the atropine group,pigs were similarly administered dichlorvos,and 0.5 hours later,atropine was injected to attain and maintain atropinization.The control group was administered saline solution.Arterial blood gas was measured at 0,0.5,1,2,4,and 6 hours post-injection.The extravascular lung water index and pulmonary vascular permeability index were recorded by the pulse-induced contour cardiac output monitor.At termination of the study,the animals were euthanized,the lung wet-to-dry weight ratio was determined,and histopathology was observed.Results In the dichlorvos group,the extravascular lung water index and pulmonary vascular permeability index were substantially increased from 0.5 hours and were particularly high within 1 hour.In the atropine group,these indices increased initially,but decreased from the 1-hour mark.The control group exhibited no obvious changes.In both the dichlorvos and atropine groups,the extravascular lung water index was negatively correlated with partial pressure of oxygen/fraction of inspiration oxygen (PO2/FiO2) and positively correlated with the pulmonary vascular permeability index.Compared with the control group,the lung wet-to-dry weight ratio markedly increased and the histopathological findings obviously changed in the dichlorvos group,but only mildly increased and changed,respectively,in the atropine group.Conclusion The extravascular lung water index is an appropriate and valuable parameter for assessment of respiratory function in acute dichlorvos poisoning.

  7. Brain injury requires lung protection

    OpenAIRE

    Lopez-Aguilar, Josefina; Blanch, Lluis

    2015-01-01

    The paper entitled “The high-mobility group protein B1-Receptor for advanced glycation endproducts (HMGB1-RAGE) axis mediates traumatic brain injury (TBI)-induced pulmonary dysfunction in lung transplantation” published recently in Science Translational Medicine links lung failure after transplantation with alterations in the axis HMGB1-RAGE after TBI, opening a new field for exploring indicators for the early detection of patients at risk of developing acute lung injury (ALI). The lung is on...

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

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    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

  9. Bilirubin/Albumin Ratio for Predicting Acute Bilirubin-induced Neurologic Dysfunction

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    Gholamreza Esmaeeli Djavid

    2011-03-01

    Full Text Available Objective:The aim of this study was to evaluate the bilirubin albumin (B/A ratio in comparison with total serum bilirubin (TSB for predicting acute bilirubin-induced neurologic dysfunction (BIND. Methods:Fifty two term and near term neonates requiring phototherapy and exchange transfusion for severe hyperbilirubinemia in Childrens Medical Center, Tehran, Iran, during September 2007 to September 2008, were evaluated. Serum albumin and bilirubin were measured at admission. All neonates were evaluated for acute BIND based on clinical findings. Findings:Acute BIND developed in 5 (3.8% neonates. B/A ratio in patients with BIND was significantly higher than in patients without BIND (P<0.001. Receiver operation characteristics (ROC analysis identified a TSB cut off value of 25 mg/dL [area under the curve (AUC 0.945] with a sensitivity of 100% and specificity of 85%. Also, according to the ROC curve, B/A ratio cut off value for predicting acute BIND was 8 (bil mg/al g (AUC 0.957 with sensitivity of 100% and specificity of 94%. Conclusion:Based on our results, we suggest using B/A ratio in conjunction with TSB. This can improve the specificity and prevent unnecessary invasive therapy such as exchange transfusion in icteric neonates.

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

    Shyamsundar, Murali; Danny F McAuley

    2008-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    2013-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damag...

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

  17. Lung tissue remodeling in the acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Souza Alba Barros de

    2003-01-01

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

  18. Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model.

    Directory of Open Access Journals (Sweden)

    Fiona E Lovegrove

    2008-05-01

    Full Text Available Although acute lung injury (ALI is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM; however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL, histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA. BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar-capillary membrane barrier-the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36(-/- mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality.

  19. Influence of renal dysfunction on clinical outcomes in patients with congestive heart failure complicating acute myocardial infarction.

    Science.gov (United States)

    Kim, Chang Seong; Kim, Min Jee; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Ahn, Young-Keun; Jeong, Myung Ho; Kim, Young Jo; Cho, Myeong Chan; Kim, Chong Jin; Kim, Soo Wan

    2013-01-01

    The clinical course and medical treatment of patients with congestive heart failure (CHF) complicating acute myocardial infarction (AMI) are not well established, especially in patients with concomitant renal dysfunction. We performed a retrospective analysis of the prospective Korean Acute Myocardial Infarction Registry to assess the medical treatments and clinical outcomes of patients with CHF (Killip classes II or III) complicated by AMI, in the presence or absence of renal dysfunction. Of 13,498 patients with AMI, 2769 (20.5%) had CHF on admission. Compared to CHF patients with preserved renal function, in-hospital mortality and major adverse cardiac events were increased both at 1 month and at 1 year after discharge in patients with renal dysfunction (1154; 41.7%). Postdischarge use of aspirin, betablockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers and statins significantly reduced the 1-year mortality rate for CHF patients with renal dysfunction; such reduction was not observed for those without renal dysfunction, except in the case of aspirin. Patients with CHF complicating AMI, which is accompanied by renal dysfunction, are at higher risk for adverse cardiovascular outcomes than patients without renal dysfunction. However, they receive fewer medications proven to reduce mortality rates.

  20. Denbinobin induces apoptosis in human lung adenocarcinoma cells via Akt inactivation, Bad activation, and mitochondrial dysfunction.

    Science.gov (United States)

    Kuo, Chen-Tzu; Hsu, Ming-Jen; Chen, Bing-Chang; Chen, Chien-Chih; Teng, Che-Ming; Pan, Shiow-Lin; Lin, Chien-Huang

    2008-02-28

    Increasing evidence demonstrated that denbinobin, isolated from Ephemerantha lonchophylla, exert cytotoxic effects in cancer cells. The purpose of this study was to investigate whether denbinobin induces apoptosis and the apoptotic mechanism of denbinobin in human lung adenocarcinoma cells (A549). Denbinobin (1-20microM) caused cell death in a concentration-dependent manner. Flow cytometric analysis and annexin V labeling demonstrated that denbinobin increased the percentage of apoptotic cells. A549 cells treated with denbinobin showed typical characteristics of apoptosis including morphological changes and DNA fragmentation. Denbinobin induced caspase 3 activation, and N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a broad-spectrum caspase inhibitor, prevented denbinobin-induced cell death. Denbinobin induced the loss of the mitochondrial membrane potential and the release of mitochondrial apoptotic proteins including cytochrome c, second mitochondria derived activator of caspase (Smac), and apoptosis-inducing factor (AIF). In addition, denbinobin-induced Bad activation was accompanied by the dissociation of Bad with 14-3-3 and the association of Bad with Bcl-xL. Furthermore, denbinobin induced Akt inactivation in a time-dependent manner. Transfection of A549 cells with both wild-type and constitutively active Akt significantly suppressed denbinobin-induced Bad activation and cell apoptosis. These results suggest that Akt inactivation, followed by Bad activation, mitochondrial dysfunction, caspase 3 activation, and AIF release, contributes to denbinobin-induced cell apoptosis. PMID:18262737

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

    OpenAIRE

    Robinder G Khemani; Newth, Christopher J.L.

    2010-01-01

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

  2. 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.

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

    Science.gov (United States)

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

    2005-08-01

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

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

    Science.gov (United States)

    Lutz, Waldemar; Stetkiewicz, Jan

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marc A Sze

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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

  10. 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

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

    Science.gov (United States)

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

    2016-10-01

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

  12. Acute Thrombocytopenia, Leucopenia, and Multiorgan Dysfunction: The First Case of SFTS Bunyavirus outside China?

    Directory of Open Access Journals (Sweden)

    Srdjan Denic

    2011-01-01

    Full Text Available We report a 57-year-old man with acute thrombocytopenia, leucopenia, and multiorgan dysfunction. Patient was from North Korea and was temporarily working in Dubai, United Arab Emirates, when he fell ill in March 2009. At the same time and unknown to us, many patients with similar clinical manifestations were admitted to hospitals in China. The Chinese cases—identified between March and July 2009—were recently reported to have been infected with a tick-born strain of bunyavirus, a new disease. The virus infection was documented in patients from central China and the region that shares the border with North Korea. The clinical manifestations, the time of disease onset, and geographical link of the patient with the region in which the disease is endemic suggest that the patient had SFTS bunyavirus infection.

  13. New therapeutic approach: diphenyl diselenide reduces mitochondrial dysfunction in acetaminophen-induced acute liver failure.

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    Nélson R Carvalho

    Full Text Available The acute liver failure (ALF induced by acetaminophen (APAP is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe2], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe2 to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe2 to the N-acetylcysteine (NAC during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg, (PhSe2 (15.6 mg/kg, NAC (1200 mg/kg, APAP+(PhSe2 or APAP+NAC, where the (PhSe2 or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe2. The effectiveness of (PhSe2 was similar at a lower dose than NAC. In summary, (PhSe2 provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.

  14. [Assessment of renal function, iatrogenic hyperkalemia and acute renal dysfunction in cardiology. Contrast-induced nephropathy].

    Science.gov (United States)

    Górriz Teruel, José Luis; Beltrán Catalán, Sandra

    2011-12-01

    Renal impairment influences the prognosis of patients with cardiovascular disease and increases cardiovascular risk. Renal dysfunction is a marker of lesions in other parts of the vascular tree and detection facilitates early identification of individuals at high risk of cardiovascular events. In patients with cardiovascular disease, renal function is assessed by measuring albuminuria in a spot urine sample and by estimating the glomerular filtration rate using creatinine-derived predictive formulas or equations. We recommend the Chronic Kidney Disease Epidemiology Collaboration or the Modification of Diet in Renal Disease formulas. The Cockcroft-Gault formula is a possible alternative. The administration of drugs that block the angiotensin-renin system can, on occasion, be associated with acute renal dysfunction or hyperkalemia. We need to know when risk of these complications exists so as to provide the best possible treatment: prevention. Given the growing number of diagnostic and therapeutic procedures in the field of cardiology that use intravenous contrast media, contrast-induced nephrotoxicity represents a significant problem. We should identify the risk factors and patients at greatest risk, and prevent it from appearing.

  15. Acute effect of phosphodiesterase type 5 inhibitor on serum oxidative status and prolidase activities in men with erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Murat Savas

    2010-01-01

    Full Text Available OBJECTIVES: To investigate the acute effect of phosphodiesterase type 5 (PDE5 inhibitor on erectile dysfunction by evaluating serum oxidative status and prolidase activity. METHODS: Serum samples of 36 patients with erectile dysfunction and 30 control cases were analyzed for total antioxidant status, total oxidant status, and prolidase activity, before and after the administration of tadalafil citrate. RESULTS: Before and after tadalafil citrate administration, serum total antioxidant status, total oxidant status, and prolidase were 1.1+0.0 vs. 1.6 + 0.0 umol H2O2 Eq/L, 10.3+1.1 vs. 6.9 + 1.2 umol H2O2 Eq/L, and 236.4+19.5 vs. 228.2 + 19.2 U/L, respectively (p<0.0001 for all. CONCLUSIONS: Evaluation of serum oxidative status and prolidase activity confirmed the beneficial acute effects of PDE5 inhibitor in patients with erectile dysfunction.

  16. Hypothalamic pituitary dysfunction in acute nonmycobacterial infections of central nervous system

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    Dinesh K Dhanwal

    2011-01-01

    Full Text Available Background and Objective: Acute and chronic central nervous system (CNS infections are not uncommon in tropical countries and are associated with high morbidity and mortality if specific targeted therapy is not instituted in time. Effects of tubercular meningitis, a form of chronic meningitis on hypothalamic pituitary axis, are well known both at the time of diagnosis and after few months to years of illness. However, there are few reports of pituitary dysfunction in subjects with acute CNS infections. Therefore, this study was aimed at evaluating the pituitary hormonal profile in patients with nonmycobacterial acute meningitis at the time of presentation. Materials and Methods: This prospective case series study included 30 untreated adult patients with acute meningitis, meningoencephalitis, or encephalitis, due to various nonmycobacterial agents, admitted and registered with Lok Nayak Hospital, Maulana Aazd Medical College, New Delhi, between September 2007 and March 2009. Patients with preexisting endocrine diseases, tubercular meningitis and patients on steroids were carefully excluded from the study. The basal pituitary hormonal profile was measured by the electrochemilumniscence technique for serum cortisol, luetinizing hormone (LH, follicular stimulating hormone (FSH, prolactin (PRL, thyrotropin (TSH, free tri-iodothyronine (fT3, and free thyroxine (fT4. Results: The cases (n = 30 comprised of patients with acute pyogenic meningitis (n = 23, viral meningoencephalitis (n = 4, brain abscess (n = 2, and cryptococcal meningitis (n = 1. The mean age of patients was 28.97 ± 11.306 years. Out of 30 patients, 14 (46.7% were males and 16 (58.1% were females. Adrenal insufficiency both absolute and relative was seen in seven (23.3% and hyperprolactinemia was seen in nine (30.0% of the patients. One study subject had central hypothyroidism and seven (23.3 showed low levels of LH and/or FSH. None of patients showed clinical features suggestive of

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

    Directory of Open Access Journals (Sweden)

    Nemat Bilan

    2016-05-01

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

  18. Acute ablation of PERK results in ER dysfunctions followed by reduced insulin secretion and cell proliferation

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    McGrath Barbara C

    2009-09-01

    Full Text Available Abstract Background A deficiency in Perk (EIF2AK3 causes multiple neonatal defects in humans known as the Wolcott Rallison syndrome. Perk KO mice exhibit the same array of defects including permanent neonatal diabetes (PND. PND in mice was previously shown by us to be due to a decrease in beta cell proliferation and insulin secretion. The aim of this study was to determine if acute ablation of PERK in the 832/13 beta cells recapitulates these defects and to identify the primary molecular basis for beta cell dysfunction. Results The INS1 832/13 transformed rat beta cell line was transduced with a dominant-negative Perk transgene via an adenoviral vector. AdDNPerk-832/13 beta cells exhibited reduced expression of insulin and MafA mRNAs, reduced insulin secretion, and reduced cell proliferation. Although proinsulin content was reduced in AdDNPerk-832/13 beta cells, proinsulin was abnormally retained in the endoplasmic reticulum. A temporal study of the acute ablation of Perk revealed that the earliest defect seen was induced expression of two ER chaperone proteins, GRP78/BiP and ERp72. The oxidized states of ERp72 and ERp57 were also increased suggesting an imbalance in the redox state of the ER. Conclusion Acute ablation of Perk in INS 832/13 beta cells exhibited all of the major defects seen in Perk KO mice and revealed abnormal expression and redox state of key ER chaperone proteins. Dysregulation of ER chaperone/folding enzymes ERp72 and GRP78/BiP occurred early after ablation of PERK function suggesting that changes in ER secretory functions may give rise to the other defects including reduced insulin gene expression, secretion, and cell proliferation.

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. 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.

  2. Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury.

    Science.gov (United States)

    Wigenstam, Elisabeth; Elfsmark, Linda; Koch, Bo; Bucht, Anders; Jonasson, Sofia

    2016-10-15

    We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl2) with the aim to understand the pathogenesis of the long-term sequelae of Cl2-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5h up to 90days after a single inhalation of Cl2. A single dose of dexamethasone (10mg/kg) was administered 1h following Cl2-exposure. A 15-min inhalation of 200ppm Cl2 was non-lethal in Sprague-Dawley rats. At 24h post exposure, Cl2-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24h but did not influence the AHR. Inhalation of Cl2 in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl2-induced respiratory dysfunction. PMID:27586366

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

    OpenAIRE

    Levitt, Joseph E.; Matthay, Michael A

    2010-01-01

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

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

    OpenAIRE

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

    2000-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    2002-01-01

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

  7. Matrix metalloproteinase inhibition attenuates right ventricular dysfunction and improves responses to dobutamine during acute pulmonary thromboembolism

    Science.gov (United States)

    Neto-Neves, Evandro M; Sousa-Santos, Ozelia; Ferraz, Karina C; Rizzi, Elen; Ceron, Carla S; Romano, Minna M D; Gali, Luis G; Maciel, Benedito C; Schulz, Richard; Gerlach, Raquel F; Tanus-Santos, Jose E

    2013-01-01

    Activated matrix metalloproteinases (MMPs) cause cardiomyocyte injury during acute pulmonary thromboembolism (APT). However, the functional consequences of this alteration are not known. We examined whether doxycycline (a MMP inhibitor) improves right ventricle function and the cardiac responses to dobutamine during APT. APT was induced with autologous blood clots (350 mg/kg) in anaesthetized male lambs pre-treated with doxycycline (Doxy, 10 mg/kg/day, intravenously) or saline. Non-embolized control lambs received doxycycline pre-treatment or saline. The responses to intravenous dobutamine (Dob, 1, 5, 10 μg/kg/min.) or saline infusions at 30 and 120 min. after APT induction were evaluated by echocardiography. APT increased mean pulmonary artery pressure and pulmonary vascular resistance index by ∼185%. Doxycycline partially prevented APT-induced pulmonary hypertension (P  0.05). RV dysfunction on stress echocardiography was observed in embolized lambs (APT+Dob group) but not in embolized animals pre-treated with doxycycline (Doxy+APT+Dob). APT increased MMP-9 activity, oxidative stress and gelatinolytic activity in the RV. Although doxycycline had no effects on RV MMP-9 activity, it prevented the increases in RV oxidative stress and gelatinolytic activity (P < 0.05). APT increased serum cardiac troponin I concentrations (P < 0.05), doxycycline partially prevented this alteration (P < 0.05). We found evidence to support that doxycycline prevents RV dysfunction and improves the cardiac responses to dobutamine during APT. PMID:24199964

  8. Consumption of Hydrogen Water Reduces Paraquat-Induced Acute Lung Injury in Rats

    Directory of Open Access Journals (Sweden)

    Shulin Liu

    2011-01-01

    Full Text Available Exposure to paraquat leads to acute lung injury and oxidative stress is widely accepted as a contributor to paraquat-induced acute lung injury. Recent studies have reported that consumption of water with dissolved molecular hydrogen to a saturated level (hydrogen water prevents oxidative stress-induced diseases. Here, we investigated whether consumption of saturated hydrogen saline protects rats against paraquat-induced acute lung injury. Adult male Sprague-Dawley (SD rats were randomly divided into four groups: Control group; hydrogen water-only group (HW group; paraquat-only group (PQ group; paraquat and hydrogen water group (PQ  +  HW group. The rats in control group and HW group drank pure water or hydrogen water; the rats in PQ group and PQ  +  HW group were intraperitonealy injected with paraquat (35 mg/kg and then provided pure water or hydrogen water. Both biochemical and histological lung alterations were measured. The results showed that hydrogen water ameliorated these alterations, demonstrating that hydrogen water alleviated paraquat-induced acute lung injury possibly by inhibition of oxidative damage.

  9. Consumption of hydrogen water reduces paraquat-induced acute lung injury in rats.

    Science.gov (United States)

    Liu, Shulin; Liu, Kan; Sun, Qiang; Liu, Wenwu; Xu, Weigang; Denoble, Petar; Tao, Hengyi; Sun, Xuejun

    2011-01-01

    Exposure to paraquat leads to acute lung injury and oxidative stress is widely accepted as a contributor to paraquat-induced acute lung injury. Recent studies have reported that consumption of water with dissolved molecular hydrogen to a saturated level (hydrogen water) prevents oxidative stress-induced diseases. Here, we investigated whether consumption of saturated hydrogen saline protects rats against paraquat-induced acute lung injury. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group; hydrogen water-only group (HW group); paraquat-only group (PQ group); paraquat and hydrogen water group (PQ + HW group). The rats in control group and HW group drank pure water or hydrogen water; the rats in PQ group and PQ + HW group were intraperitonealy injected with paraquat (35 mg/kg) and then provided pure water or hydrogen water. Both biochemical and histological lung alterations were measured. The results showed that hydrogen water ameliorated these alterations, demonstrating that hydrogen water alleviated paraquat-induced acute lung injury possibly by inhibition of oxidative damage. PMID:21318114

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

    Science.gov (United States)

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

    2007-01-01

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

  11. Research progress on obesity and acute lung injury%肥胖与急性肺损伤研究进展

    Institute of Scientific and Technical Information of China (English)

    钱永兵; 王瑞兰

    2011-01-01

    In 2009, H1N1 outbreaks worldwidely,epidemiological studies have found that obesity becomes an independent risk factor of high mortality in patients infected with H 1 N1 virus. Because obesity can cause physiological and biochemical changes, patients may be more complicated with acute lung injury.Obesity can cause inflammation, endothelial dysfunction and oxidative stress in patients with acute lung injury. This article reviews obesity and pathogenesis of acute lung injury.%2009年的H1N1爆发,流行病学研究发现肥胖为H1N1病毒感染高死亡率的独立危险因素.由于肥胖可引起生理生化改变,可能更易并发急性肺损伤;肥胖能引起急性肺损伤患者炎症、内皮功能损害和氧应激等变化.现就肥胖与急性肺损伤的发病机制作一综述.

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

    OpenAIRE

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jing Wang

    1999-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    Science.gov (United States)

    Gupta, Arjun; Sen, Shiraj; Naina, Harris

    2016-01-01

    Bleomycin-induced lung injury is the most common chemotherapy-associated lung disease, and is linked with several histopathological patterns. Acute fibrinous and organising pneumonia (AFOP) is a relatively new and rare histological pattern of diffuse lung injury. We report the first known case of bleomycin-induced AFOP. A 36-year-old man with metastatic testicular cancer received three cycles of bleomycin, etoposide and cisplatin, before being transitioned to paclitaxel, ifosfamide and cisplatin. He subsequently presented with exertional dyspnoea, cough and pleuritic chest pain. CT of the chest demonstrated bilateral ground glass opacities with peribronchovascular distribution and pulmonary function tests demonstrated a restrictive pattern of lung disease with impaired diffusion. Transbronchial biopsy revealed intra-alveolar fibrin deposits with organising pneumonia, consisting of intraluminal loose connective tissue consistent with AFOP. The patient received high-dose corticosteroids with symptomatic and radiographic improvement. AFOP should be recognised as a histopathological variant of bleomycin-induced lung injury. PMID:27053543

  16. 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.

  17. Thin-section computed tomography findings before and after azithromycin treatment of neutrophilic reversible lung allograft dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Pim A. de [Department of Radiology, Katholieke Universiteit Leuven, Leuven (Belgium); Lung Transplantation Unit, Katholieke Universiteit Leuven, Leuven (Belgium); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vos, Robin; Verleden, Geert M.; Vanaudenaerde, Bart M. [Lung Transplantation Unit, Katholieke Universiteit Leuven, Leuven (Belgium); Verschakelen, Johny A. [Department of Radiology, Katholieke Universiteit Leuven, Leuven (Belgium)

    2011-12-15

    Recently a novel subgroup of bronchiolitis obliterans syndrome (BOS) has been described in patients after lung transplantation with high neutrophil counts in broncho-alveolar lavage and recovery of lung functional decline with azithromycin treatment. We aimed to describe the thin-section computed tomography (CT) findings of these neutrophilic reversible allograft dysfunction (NRAD) patients before and after azithromycin. A cohort of 100 lung transplant recipients with BOS were treated with azithromycin and underwent lung function testing, broncho-alveolar lavage and CT before azithromycin treatment and during follow-up. The 200 CT data sets were scored for bronchial dilatation, mucus plugging, centrilobular abnormalities, airway wall thickening, consolidation, ground glass and end-expiratory air trapping. NRAD was characterized by more centrilobular abnormalities on CT (p = 0.03 for prevalence and p = 0.06 for severity) compared to non-responders. At follow-up NRAD patients showed improvement in all CT abnormalities including air trapping, but the degree of improvement in all CT abnormalities was significantly different between responders and non-responders (who showed progression of bronchus dilatation, consolidation and air trapping). Within BOS patients those with NRAD differ from azithromycin non-responders by more centrilobular abnormalities on CT before azithromycin and improvement in bronchus dilatation, consolidation and air trapping during treatment. (orig.)

  18. Attenuation of acute lung inflammation induced by cigarette smoke in CXCR3 knockout mice

    Directory of Open Access Journals (Sweden)

    Cheng Deyun

    2008-12-01

    Full Text Available Abstract Background CD8+ T cells may participate in cigarette smoke (CS induced-lung inflammation in mice. CXCL10/IP-10 (IFNγ-inducible protein 10 and CXCL9/Mig (monokine induced by IFN-γ are up-regulated in CS-induced lung injury and may attract T-cell recruitment to the lung. These chemokines together with CXCL11/ITAC (IFN-inducible T-cell alpha chemoattractant are ligands for the chemokine receptor CXCR3 which is preferentially expressed chiefly in activated CD8+ T cells. The purpose of this investigation was to study the contribution of CXCR3 to acute lung inflammation induced by CS using CXCR3 knockout (KO mice. Methods Mice (n = 8 per group were placed in a closed plastic box connected to a smoke generator and were exposed whole body to the tobacco smoke of five cigarettes four times a day for three days. Lung pathological changes, expression of inflammatory mediators in bronchoalveolar lavage (BAL fluid and lungs at mRNA and protein levels, and lung infiltration of CD8+ T cells were compared between CXCR3-/- mice and wild type (WT mice. Results Compared with the WT littermates, CXCR3 KO mice showed less CS-induced lung inflammation as evidenced by less infiltration of inflammatory cells in airways and lung tissue, particularly fewer CD8+ T cells, lower levels of IFNγ and CXCR3 ligands (particularly CXCL10. Conclusion Our findings show that CXCR3 is important in promoting CD8+ T cell recruitment and in initiating IFNγ and CXCL10 release following CS exposure. CXCR3 may represent a promising therapeutic target for acute lung inflammation induced by CS.

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

    OpenAIRE

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Abdulzahra Hussain

    2012-11-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    OpenAIRE

    Bitzén, Ulrika

    2006-01-01

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

  4. Predicting outcomes over time in patients with heart failure, left ventricular systolic dysfunction, or both following acute myocardial infarction

    OpenAIRE

    Lopes, Renato D.; Pieper, Karen S.; Stevens, Susanna R.; Solomon, Scott D.; McMurray, John J.V.; Pfeffer, Marc A.; Leimberger, Jeffrey D.; Velazquez, Eric J.

    2016-01-01

    Background: Most studies of risk assessment or stratification in patients with myocardial infarction (MI) have been static and fail to account for the evolving nature of clinical events and care processes. We sought to identify predictors of mortality, cardiovascular death or nonfatal MI, and cardiovascular death or nonfatal heart failure (HF) over time in patients with HF, left ventricular systolic dysfunction, or both post‐MI. Methods and Results: Using data from the VALsartan In Acute m...

  5. Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity

    OpenAIRE

    Beno W Oppenheimer; Berger, Kenneth I.; Ali, Saleem; Segal, Leopoldo N.; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M.

    2016-01-01

    Rationale Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. Objectives We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) t...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Golson Maria L

    2005-06-01

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

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

    OpenAIRE

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

    2014-01-01

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

  9. 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.

  10. CARDIOPULMONARY BYPASS WITH AUTOLOGOUS LUNG AS SUBSTITUTE FOR ARTIFICIAL OXYGENATOR ATTENUATES INFLAMMATORY RESPONSIVE INSPIRATORY DYSFUNCTION

    Institute of Scientific and Technical Information of China (English)

    HUANG Hui-min; KONG Xiang; WANG Wei; ZHU De-ming; ZHANG Hai-bo

    2007-01-01

    Objective To study if using autologous lung as a substitute of oxygenator in cardiopulmonary bypass is better than the conventional cardiopulmonary bypass with artificial oxygenator in pulmonary preservation.Methods Twelve piglets were randomly divided into two groups ( n = 6). The isolated lung perfusion model was established. The experimental animals underwent continuous lung perfusion for about 120 min. While the control animals underwent 90 min lung ischemia followed by 30 min reperfusion. Another 12 piglets were randomly divided into two groups ( n =6). The experimental animals underwent bi-ventricular bypass with autologous lung perfusion.While control animals underwent conventional cardiopulmonary bypass with artificial oxygenator. The bypass time and aortic cross clamping time were 135 min and 60 min respectively for each animal. The lung static compliance ( Cstat), alveolus-artery oxygen difference ( PA-aO2 ), TNF-α, IL-6 and wet to dry lung weight ratio (W/D) were measured. Histological and ultra-structural changes of the lung were also observed after bypass. Results After either isolated lung perfusion or cardiopulmonary bypass, the Cstat decreased, the PA-aO2 increased and the content of TNF-α increased for both groups, but the changes of experimental group were much less than those of control group. The lower W/D ratio and mild pathological changes in experimental group than those in control group were also demonstrated. Conclusion Autologous lung is able to tolerate the nonpalsatile perfusion. It can be used as a substitute to artificial ogygenator in cardiopulmonary bypass to minimize the inflammatory pulmonary injury caused mainly by ischemic reperfusion and interaction of the blood to the non-physiological surface of artificial oxygenator.

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

    Directory of Open Access Journals (Sweden)

    Yang Xu

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

  12. 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.

  13. Combined venoarterial extracorporeal membrane oxygenation and transcatheter aortic valve implantation for the treatment of acute aortic prosthesis dysfunction in a high-risk patient.

    Science.gov (United States)

    Pergolini, Amedeo; Zampi, Giordano; Tinti, Maria Denitza; Polizzi, Vincenzo; Pino, Paolo Giuseppe; Pontillo, Daniele; Musumeci, Francesco; Luzi, Giampaolo

    2016-01-01

    We describe the case of a patient with acute bioprosthesis dysfunction in cardiogenic shock, in whom hemodynamic support was provided by venoarterial extracorporeal membrane oxygenation, and successfully treated by transcatheter aortic valve implantation.

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

    Science.gov (United States)

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

    2016-02-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2012-09-01

    Although non-small cell lung cancer (NSCLC) can metastasize to almost any organ, metastasis to the gallbladder with significant clinical manifestation is relatively rare. Here, we report a case of gallbladder metastasis of NSCLC presenting as acute cholecystitis. A 79-year-old man presented with pain in the right upper quadrant and fever. A computed tomography (CT) scan of the chest and abdomen showed a cavitary mass in the right lower lobe of the lung and irregular wall thickening of the gallbladder. Open cholecystectomy and needle biopsy of the lung mass were performed. Histological examination of the gallbladder revealed a moderately-differentiated squamous cell carcinoma displaying the same morphology as the lung mass assessed by needle biopsy. Subsequent immunohistochemical examination of the gallbladder and lung tissue showed that the tumor cells were positive for P63 but negative for cytokeratin 7, cytokeratin 20 and thyroid transcription factor-1. A second primary tumor of the gallbladder was excluded by immunohistochemical methods, and the final pathological diagnosis was gallbladder metastasis of NSCLC. Although the incidence is extremely rare, acute cholecystitis can occur in association with lung cancer metastasis to the gallbladder. PMID:23358590

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  18. 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.

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

    OpenAIRE

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

    2015-01-01

    Background: Subsequent neutrophil (polymorphonuclear neutrophil [PMN])-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI), and mesenchymal stem cell (MSC) can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair of VILI. However, whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown. This study aimed to test whether MSC intervention could attenuate the PM...

  20. [Serrapeptase-induced lung injury manifesting as acute eosiniphilic pneumonia].

    Science.gov (United States)

    Sasaki, S; Kawanami, R; Motizuki, Y; Nakahara, Y; Kawamura, T; Tanaka, A; Watanabe, S

    2000-07-01

    An 84-year-old man was referred to our hospital because of fever, cough, and hemoptysis. The patient had acute respiratory failure (PaO2 < 40 mmHg) on admission, with diffuse interstitial infiltration and bilateral pleural effusion. The bronchoalveolar lavage fluid was bloody, and contained a high percentage of eosinophils (32%). A diagnosis of acute eosinophilic pneumonia was established, and the patient made a rapid recovery after corticosteroids were administered. When the DLST (drug lymphocyte stimulation test) was performed after the corticosteroid therapy was stopped, it was positive for serrapeptase, which had been prescribed for chronic cystitis for 3 months before the onset of the pneumonia. This was a case of drug (serrapeptase)-induced pneumonitis manifesting as acute eosinophilic pneumonia.

  1. Radiological patterns of primary graft dysfunction after lung transplantation evaluated by 64-multi-slice computed tomography: a descriptive study.

    Science.gov (United States)

    Belmaati, Esther Okeke; Steffensen, Ida; Jensen, Claus; Kofoed, Klaus F; Mortensen, Jann; Nielsen, Michael B; Iversen, Martin

    2012-06-01

    We evaluated the diagnostic value of high-resolution computed tomography (HRCT) images generated from 64 detector multi-slice CT scanners (HRCT(64-MSCT) imaging) in relation to primary graft dysfunction (PGD) after lung-transplantation (LUTX) in a pilot study. PGD has mortality rates ranging from 17 to 50% over a 90-day period. Detailed HRCT lung images, reconstructed using 64-MSCT, may aid diagnostic and therapeutic efforts in PGD. Thirty-two patients were scanned four times within a year post-LUTX, in a single-centre prospective study. HRCT lung images were reviewed, evaluated and scored by two observers, for ground-glass (GG) opacities, consolidation, septal thickening (ST) and pulmonary embolism. Image and PGD scores were compared in each patient. GG and consolidation changes were largely present up until 2 weeks post-LUTX, and markedly reduced by the 12th week. ST was predominantly found in patients with PGD. There were no vascular changes found at CT angiographies. The most severe cases of GG opacities and consolidation were found in patients with PGD. ST seems to be an important indicator of PGD. HRCT(64-MSCT) imaging may be a useful tool for the identification of pathological features of PGD not detected by classical evaluation in patients undergoing LUTX. PMID:22378316

  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. Distress and alexithymia in lung recipients - psychosocial strains and associations with chronic allograft dysfunction

    OpenAIRE

    Goetzmann, L; Irani, S; Schwegler, K.; Stamm, M.; Bricman, R; Buddeberg, C; Schmid, C.; Benden, C; Klaghofer, R; Boehler, A

    2010-01-01

    QUESTIONS UNDER STUDY: In recent years, distress and alexithymia have been recognised as psychosocial factors related to both somatic and psychosomatic diseases. In this study distress and alexithymia and their associations with physical parameters were investigated in lung recipients. METHODS: The study, which included 76 patients after a lung transplant, measured psychological distress (Symptom Checklist, SCL-K-9) and alexithymia (Toronto Alexithymia Scale, TAS-20). Physical health was asse...

  4. Noninvasive Investigations for the Early Detection of Chronic Airways Dysfunction Following Lung Transplantation

    OpenAIRE

    Cook, Richard C.; Guy Fradet; Nestor L Muller; Daniel F Worsley; David Ostrow; Levy, Robert D

    2003-01-01

    BACKGROUND: The diagnosis of chronic rejection after lung transplantation is limited by the lack of a reliable test to detect airways disease early.OBJECTIVES: To determine whether maximum midexpiratory flow (MMEF), or changes on high resolution computed tomography (HRCT) or ventilation/perfusion lung (V/Q) scans are sensitive and specific for early detection of bronchiolitis obliterans syndrome (BOS; forced expiratory volume in 1 s [FEV1] less than 80% post-transplant baseline) by evaluating...

  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

    2011-04-01

    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.

  6. 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

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

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    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.

  8. Melatonin reduces acute lung inflammation, edema,and hemorrhage in heatstroke rats

    Institute of Scientific and Technical Information of China (English)

    Wen-shiann WU; Ming-ting CHOU; Chien-ming CHAO; Chen-kuei CHANG; Mao-tsun LIN; Ching-ping CHANG

    2012-01-01

    Aim:To assess the therapeutic effect of melatonin on heat-induced acute lung inflammation and injury in rats.Methods:Heatstroke was induced by exposing anesthetized rats to heat stress (36 ℃,100 min).Rats were treated with vehicle or melatonin (0.2,1,5 mg/kg) by intravenous administration 100 min after the initiatioin of heatstroke and were allowed to recover at room temperature (26 ℃).The acute lung injury was quantified by morphological examination and by determination of the volume of pleural exudates,the number of polymorphonuclear (PMN) cells,and the myeloperoxidase (MPO) activity.The concentrations of tumor necrosis factor,interleukin (IL)-1β,IL-6,and IL-10 in bronchoalveolar fluid (BALF) were measured by ELISA.Nitric oxide (NO)level was determined by Griess method.The levels of glutamate and lactate-to-pyruvate ratio were analyzed by CMA600 microdialysis analyzer.The concentrations of hydroxyl radicals were measured by a procedure based on the hydroxylation of sodium salicylates leading to the production of 2,3-dihydroxybenzoic acid (DHBA).Results:Melatonin (1 and 5 mg/kg ) significantly (i) prolonged the survival time of heartstroke rats (117 and 186 min vs 59 min); (ii)attenuated heatstroke-induced hyperthermia and hypotension; (iii) attenuated acute lung injury,including edema,neutrophil infiltration,and hemorrhage scores; (iv) down-regulated exudate volume,BALF PMN cell number,and MPO activity; (v) decreased the BALF levels of lung inflammation response cytokines like TNF-alpha,interleukin (IL)-1β,and IL-6 but further increased the level of an anti-inflammatory cytokine IL-10; (vi) reduced BALF levels of glutamate,lactate-to-pyruvate ratio,NO,2,3-DHBA,and lactate dehydrogenase.Conclusion:Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung inflammation and injury.

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

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    Zohreh Poursaleh

    2012-09-01

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

  10. 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.

  11. [Current approaches to the treatment of severe hypoxic respiratory insufficiency (acute lung injury; acute respiratory distress syndrome)].

    Science.gov (United States)

    Kluge, S; Müller, T; Pfeifer, M

    2011-02-01

    Lung-protective ventilation with a low tidal volume, plateau pressure 90% and permissive hypercapnia results in reduction of the mortality rate in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The level of the positive end-expiratory pressure (PEEP) must be chosen in relation to oxygen requirement. High frequency oscillatory ventilation and neurally adjusted ventilatory assist are promising methods. However, further studies with firm end-points have to be awaited before a final judgment is possible. Veno-venous extracorporeal membrane oxygenation (ECMO) can ensure life-sustaining gas exchange in patients with severe vitally compromised pulmonary failure, to provide time for lung tissue to heal and reduce ventilatory stress. The latest guidelines for analgesia and sedation in intensive care medicine demand consistent monitoring of the level of sedation and the intensity of pain. The sedation should be interrupted daily, with phases of awakenings and, if possible, spontaneous breathing. Methods of supportive treatment: Positional treatment (prone position) and inhalation of vasodilators can improve ventilation/perfusion mismatch and thus oxygenation. However, administration of surfactant is currently not advised in adult respiratory failure. PMID:21271478

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

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    Zhongchen Zhang

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

  13. HLA-E(⁎)01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence.

    Science.gov (United States)

    Di Cristofaro, Julie; Pelardy, Mathieu; Loundou, Anderson; Basire, Agnès; Gomez, Carine; Chiaroni, Jacques; Thomas, Pascal; Reynaud-Gaubert, Martine; Picard, Christophe

    2016-01-01

    Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E(⁎)01:01 and HLA-E(⁎)01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E(⁎)01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E(⁎)01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort. PMID:27493971

  14. HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

    Directory of Open Access Journals (Sweden)

    Julie Di Cristofaro

    2016-01-01

    Full Text Available Lung transplantation (LTx is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD. HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p=0.01. In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12, p=0.047. HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-12-28

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

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

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    Priscila Cilene León Bueno de Camargo

    2014-08-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

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    Xun Liang

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

  20. Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice

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    Lee, Ye-Ji [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Lee, Seung-Hae [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Youn, Young-So; Choi, Ji-Yeon [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Song, Keung-Sub [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Cho, Min-Sun [Department of Pathology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Kang, Jihee Lee, E-mail: jihee@ewha.ac.kr [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of)

    2012-08-15

    Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ►Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ►Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ►TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

  1. Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice

    International Nuclear Information System (INIS)

    Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ►Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ►Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ►TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

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

    Science.gov (United States)

    Walther, Frans J; Hernández-Juviel, José M; Gordon, Larry M; Waring, Alan J

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Frans J. Walther

    2014-05-01

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

  4. 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.

  5. 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

  6. The level of telomere dysfunction determines the efficacy of telomerase-based therapeutics in a lung cancer cell line.

    Science.gov (United States)

    Pantic, Milena; Zimmermann, Stefan; Waller, Cornelius F; Martens, Uwe M

    2005-05-01

    Telomerase is the ribonucleoprotein enzyme that maintains telomeres of eukaryotic chromosomes. Activation of telomerase is a common feature of the majority of human cancers, and inhibition of this enzyme has been proposed as a novel target for cancer therapeutics. Here, we investigated the effects of telomerase inhibition in the non-small cell lung cancer cell line NCI-H460, using a genetic approach by ectopic expression of dominant-negative (DN)-hTERT. Five clones were selected in which telomerase activity was completely abolished. As a result, telomere erosion was observed leading to proliferation arrest after a lag period of 20-28 population doublings. Although overall telomere length was similar between the different clones as measured by quantitative fluorescence in situ hybridization (Q-FISH), striking differences were found in telomere length of individual chromosomes. In particular, lack of individual telomeres and formation of end-to-end fusions were variable. Interestingly, this level of individual telomere dysfunction was positively correlated with the remaining life span of the different clones in vitro. In addition, the amount of telomere dysfunction induced by DN-hTERT was twice as high compared to the small molecule telomerase inhibitor BIBR1532, which induced growth arrest after >100 population doublings. Thus, pharmacological strategies that aim at inhibition of telomerase in cancer cells should take into account that not only overall telomere shortening, but rapid induction of a high level telomere dysfunction appears to be the crucial surrogate parameter for the development of future telomerase-based therapeutics.

  7. Logistic ex Vivo Lung Perfusion for Hyperimmunized Patients.

    Science.gov (United States)

    De Wolf, Julien; Puyo, Philippe; Bonnette, Pierre; Roux, Antoine; Le Guen, Morgan; Parquin, François; Chapelier, Alain; Sage, Edouard

    2016-09-01

    Hyperimmunized patients have restricted access to lung transplantation because of the low rate of donor lung availability. Sensitization to human leukocyte antigen is associated with acute rejection, allograft dysfunction, and decreased survival. Prospective crossmatching could allow matching a lung graft with the recipient; however, such a strategy would increase graft ischemia, with a worse impact on the long-term results of lung transplantation. We used logistic ex vivo lung perfusion for 3 patients at the Foch Hospital while waiting for a negative result of the prospective crossmatching and then moved forward to lung transplantation. All patients are alive 3 years after bilateral lung transplantation. PMID:27549543

  8. A Case of Fatal Acute Lung Injury after Balloon Valvuloplasty of Pulmonary Stenosis: Case Report and Review of Literature

    OpenAIRE

    Ostovan Mohammad Ali; Kamali Maliheh; Zolghadrasli Abdolali

    2015-01-01

    A newly described immediate complication after percutaneous pulmonary valvuloplasty is acute lung injury. Here we report a case of fatal acute lung injury after pulmonary valvuloplasty.The patient was a 26-year-old woman, referred to a general hospital with the diagnosis of livercirrhosis. In her work-ups severe pulmonary stenosis was detected and so a decision was madeto relieve the valve stenosis. Despite the procedural success, the patient developed severe dyspneaand desaturation a few hou...

  9. 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.

  10. Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats

    OpenAIRE

    Hagiwara, Satoshi; Iwasaka, Hideo; Hidaka, Seigo; Hishiyama, Sohei; Noguchi, Takayuki

    2008-01-01

    Introduction Systemic inflammatory mediators, including high mobility group box 1 (HMGB1), play an important role in the development of sepsis. Anticoagulants, such as danaparoid sodium (DA), may be able to inhibit sepsis-induced inflammation, but the mechanism of action is not well understood. We hypothesised that DA would act as an inhibitor of systemic inflammation and prevent endotoxin-induced acute lung injury in a rat model. Methods We used male Wistar rats. Animals in the intervention ...

  11. TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants

    OpenAIRE

    Hartmann, Erik K.; Thomas, Rainer; Liu, Tanghua; Stefaniak, Joanna; Ziebart, Alexander; Duenges, Bastian; Eckle, Daniel; Markstaller, Klaus; David, Matthias

    2014-01-01

    Background Inhalation of TIP peptides that mimic the lectin-like domain of TNF-α is a novel approach to attenuate pulmonary oedema on the threshold to clinical application. A placebo-controlled porcine model of acute respiratory distress syndrome (ARDS) demonstrated a reduced thermodilution-derived extravascular lung water index (EVLWI) and improved gas exchange through TIP peptide inhalation within three hours. Based on these findings, the present study compares a single versus a repetitive ...

  12. The functional comorbidity index had high inter-rater reliability in patients with acute lung injury

    OpenAIRE

    Fan Eddy; Gifford Jeneen M; Chandolu Satish; Colantuoni Elizabeth; Pronovost Peter J; Needham Dale M

    2012-01-01

    Abstract Background The Functional Comorbidity Index (FCI) was recently developed to predict physical function in acute lung injury patients using comorbidity data. Our objectives were to determine: (1) the inter-rater reliability of the FCI collected using in-patient discharge summaries (primary objective); and (2) the accuracy and predictive validity of the FCI collected using hospital discharge summaries and admission records versus complete chart review (secondary objectives). Methods For...

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

    OpenAIRE

    Bosmann, Markus; Ward, Peter A.

    2012-01-01

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

  14. Evaluation of lung recruitment maneuvers in acute respiratory distress syndrome using computer simulation

    OpenAIRE

    Das(2), Anup; Cole, Oana; Chikhani, Marc; Wang, Wenfei; Ali, Tayyba; Haque, Mainul; Bates, Declan G; Hardman, Jonathan G

    2015-01-01

    Introduction Direct comparison of the relative efficacy of different recruitment maneuvers (RMs) for patients with acute respiratory distress syndrome (ARDS) via clinical trials is difficult, due to the heterogeneity of patient populations and disease states, as well as a variety of practical issues. There is also significant uncertainty regarding the minimum values of positive end-expiratory pressure (PEEP) required to ensure maintenance of effective lung recruitment using RMs. We used patie...

  15. Effects of overinflation on procollagen type III expression in experimental acute lung injury

    OpenAIRE

    de Carvalho, Maria-Eudóxia Pilotto; Dolhnikoff, Marisa; Meireles, Sibele Inácio; Reis, Luiz Fernando Lima; Martins, Milton Arruda; Deheinzelin, Daniel

    2007-01-01

    Introduction In acute lung injury (ALI), elevation of procollagen type III (PC III) occurs early and has an adverse impact on outcome. We examined whether different high-inflation strategies of mechanical ventilation (MV) in oleic acid (OA) ALI alter regional expression of PC III. Methods We designed an experimental, randomized, and controlled protocol in which rats were allocated to two control groups (no injury, recruited [alveolar recruitment maneuver after tracheotomy without MV; n = 4 ra...

  16. A practical protocol for titrating "optimal" PEEP in acute lung injury: recruitment maneuver and PEEP decrement.

    OpenAIRE

    Suh, Gee Young; Kwon, O Jung; Yoon, Jong Wook; Park, Sang Joon; Ham, Hyoung Suk; Kang, Soo Jung; Koh, Won-Jung; Chung, Man Pyo; Kim, Ho Joong

    2003-01-01

    This study was conducted to evaluate the effectiveness and safety of a practical protocol for titrating positive end-expiratory pressure (PEEP) involving recruitment maneuver (RM) and decremental PEEP. Seventeen consecutive patients with acute lung injury who underwent PEEP titration were included in the analysis. After baseline ventilation, RM (continuous positive airway pressure, 35 cm H2O for 45 sec) was performed and PEEP was increased to 20 cmH2O or the highest PEEP guaranteeing the mini...

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

    Directory of Open Access Journals (Sweden)

    Kus T

    2015-06-01

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

  18. [Protective effect of curcumin on oleic-induced acute lung injury in rats].

    Science.gov (United States)

    Zhu, Rui-fang; Zhou, Min; He, Jian-lin; Ding, Fu-yun; Yu, Shu-qin; Xu, Guang-lin

    2008-09-01

    To investigate the effect of curcumine on acute lung injury induced by oleic acid in rat and the possible mechanism of action. The rats were divided into 6 groups randomly: normal group, control group, curcumine groups (5, 10, 20 mg x kg(-1)) and dexamethasone group (1 mg x kg(-1)). During the experiment, acute lung injury was induced by oleic acid in rat. The changes of dynamic lung compliance were recorded by anrise 2005 pulmonary function test apparatus, light microscope was used to examine histological changes and lung index as well as wet to dry weight ratio was calculated by weighting method. Lung vascular permeability and protein level in BALF were detected by ultraviolet spectrophotometry, and the concentrations of TNF-alpha, IL-6 and IL-10 in BALF were measured by enzyme linked immunosorbent assay (ELISA). The result showed that the changes of pulmonary compliance were inhibited and pulmonary function was improved by curcumine. The OA-induced elevation of lung index was restrained, as well as wet to dry weight ratio, lung vascular permeability, protein level, TNF-alpha (250.4 +/- 21.6 vs. 172.53 +/- 14.88, 122.2 +/- 10.98, 108.69 +/- 3.39) ng x L(-1), IL-6 (763.6 +/- 88.33 vs. 207.41 +/- 15.55, 172.13 +/- 21.91, 142.92 +/- 4.32) ng x L(-1) in BALF in curcumine groups, IL-10 (98.90 +/- 2.99 vs. 208.44 +/- 16.30, 218.43 +/- 6.23, 252.70 +/- 20.58) ng x L(-1) in BALF was increased, respectively significantly. Light microscope findings shown that the impairment in curcumine groups was far less severe than that in model groups. Pretreatment of curcumine showed beneficial effect on acute lung injury induced by oleic acid in rats. The mediation of both proinflammatory factor and anti-inflammatory factor by curcumine may be involved in mechanism of action of curcumine effects. PMID:19066061

  19. Thallium lung uptake images (TLI) in patients with acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takeshi; Kimata, Shinichi; Hirosawa, Koshichiro

    1985-03-01

    To determine whether thallium lung uptake images (TLI) can be used as a noninvasive method to estimate any of hemodynamic changes in patients with acute myocardial infarction (AMI), TLI were evaluated in 23 patients with AMI. TLI were easily obtained for additional 5 minutes following conventional myocardial imaging. All patients underwent multigated blood pool imagings and cardiac catheterization. TLI were estimated by comparing maximal lung counts with maximal myocardial counts (thallium lung heart ratio: LHR). Patients were classified to G-0 (0.6 > LHR), G-1 (0.8 > LHR >= 0.6) and G-2 (LHR >= 0.8). Mean pulmonary artery wedge pressure (mPw) and ejection fraction (EF) of G-0 (7 patients), G-1 (7 patients) and G-2 (9 patients) were 11.4 +- 4.2, 16.9 +- 4.1, 21.1 +- 4.7 mmHg and 51.4 +- 9.7, 42.7 +- 6.7, 23.5 +- 5.6% respectively. This classification was statistically significant. Good correlation (mPw = 1.1 + 21.3 LHR, r = 0.75 and EF = 80.2 - 57.3 LHR, r=-0.85) was obtained. The specificity of G-0 for mPw < 18 mmHg was 100% (10/10) and that of G-2 for EF <= 30% was also 100% (13/13). From various types of TLI it was noted that thallium-201 did not accumulate uniformly over lung area and usually maximal thallium-201 lung uptake was noted at basal zone of right lung. Thallium-201 lung uptake in the upper zone of lung might increase according to hemodynamic deterioration. TLI were clinically useful images for separating high and low risk groups of patients with AMI.

  20. Sildenafil and diastolic dysfunction after acute myocardial infarction in patients with preserved ejection fraction

    DEFF Research Database (Denmark)

    Andersen, Mads J; Ersbøll, Mads; Axelsson, Anna;

    2013-01-01

    BACKGROUND: Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients...... with diastolic dysfunction after myocardial infarction. METHODS AND RESULTS: Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9...... in the placebo group. CONCLUSIONS: Sildenafil did not decrease filling pressure at rest or during exercise in post-myocardial infarction patients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies....

  1. Sexual dimorphism in lung function responses to acute influenza A infection

    Science.gov (United States)

    Larcombe, Alexander N.; Foong, Rachel E.; Bozanich, Elizabeth M.; Berry, Luke J.; Garratt, Luke W.; Gualano, Rosa C.; Jones, Jessica E.; Dousha, Lovisa F.; Zosky, Graeme R.; Sly, Peter D.

    2011-01-01

    Please cite this paper as: Larcombe et al. (2011) Sexual dimorphism in lung function responses to acute influenza A infection. Influenza and Other Respiratory Viruses 5(5), 334–342. Background  Males are generally more susceptible to respiratory infections; however, there are few data on the physiological responses to such infections in males and females. Objectives  To determine whether sexual dimorphism exists in the physiological/inflammatory responses of weanling and adult BALB/c mice to influenza. Methods  Weanling and adult mice of both sexes were inoculated with influenza A or appropriate control solution. Respiratory mechanics, responsiveness to methacholine (MCh), viral titre and bronchoalveolar lavage (BAL) cellular inflammation/cytokines were measured 4 (acute) and 21 (resolution) days post‐inoculation. Results  Acute infection impaired lung function and induced hyperresponsiveness and cellular inflammation in both sexes at both ages. Males and females responded differently with female mice developing greater abnormalities in tissue damping and elastance and greater MCh responsiveness at both ages. BAL inflammation, cytokines and lung viral titres were similar between the sexes. At resolution, all parameters had returned to baseline levels in adults and weanling males; however, female weanlings had persisting hyperresponsiveness. Conclusions  We identified significant differences in the physiological responses of male and female mice to infection with influenza A, which occurred in the absence of variation in viral titre and cellular inflammation. PMID:21668688

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  3. Does granulocyte colony-stimulating factor exacerbate radiation-induced acute lung injury in rats?

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Gouji; Awaya, Hitomi; Matsumoto, Tsuneo; Tanaka, Nobuyuki; Matsunaga, Naofumi [Yamaguchi Univ., Ube (Japan). School of Medicine

    2000-08-01

    Radiation pneumonitis (RP) frequently occurs as a complication of thoracic irradiation. However, the mechanism of RP is not well known. Activated neutrophils are a possible pathogenesis of RP. Neutrophil activation induced by granulocyte colony-stimulating factor (G-CSF) may exacerbate RP. We studied the effects of recombinant human G-CSF on acute lung injury induced by thoracic irradiation using rats. Animals were divided into three groups: sham irradiation with saline control, irradiation alone, and irradiation with G-CSF. Actual irradiation was given as a single fraction of 16 Gy delivered to the right hemithorax. G-CSF at a dose of 12 {mu}g/body was administered subcutaneously once a day from 14 to 18 days after actual irradiation. Lung injury was evaluated 21 days after irradiation by bronchoalveolar lavage (BAL) fluid findings and the lung wet/dry weight (W/D) ratio. Neutrophil and lymphocyte counts in BAL fluid and the W/D ratio were significantly increased in the irradiation alone and the irradiation with G-CSF groups compared with those of the sham irradiation+saline control group. However, there was no significant difference observed between the irradiation alone and irradiation with G-CSF groups. In conclusion, this study suggests that postradiation administration of G-CSF does not exacerbate acute lung injury induced by thoracic irradiation in rats. (author)

  4. 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.

  5. Deep Hypothermic Circulatory Arrest with Lung Perfusion/Ventilation in a Patient with Acute Type A Aortic Dissection

    Directory of Open Access Journals (Sweden)

    Yiliam F. Rodriguez-Blanco

    2012-01-01

    Full Text Available A 50-year-old black male presented with acute type A aortic dissection. Surgical repair was performed under deep hypothermic circulatory arrest (DHCA with lung perfusion/ventilation throughout the procedure. Details of the lung perfusion technique and its potential benefits and drawbacks are discussed.

  6. Deep Hypothermic Circulatory Arrest with Lung Perfusion/Ventilation in a Patient with Acute Type A Aortic Dissection

    OpenAIRE

    Yiliam F Rodriguez-Blanco; Lester Garcia; Tania Brice; Marco Ricci; Salerno, Tomas A.

    2012-01-01

    A 50-year-old black male presented with acute type A aortic dissection. Surgical repair was performed under deep hypothermic circulatory arrest (DHCA) with lung perfusion/ventilation throughout the procedure. Details of the lung perfusion technique and its potential benefits and drawbacks are discussed.

  7. 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.

  8. Neutralization of Osteopontin Ameliorates Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion.

    Science.gov (United States)

    Hirano, Yohei; Aziz, Monowar; Yang, Weng-Lang; Ochani, Mahendar; Wang, Ping

    2016-10-01

    Intestinal ischemia-reperfusion (I/R) is associated with acute respiratory distress syndrome. Osteopontin (OPN), a glycoprotein secreted from immune-reactive cells, plays a deleterious role in various inflammatory diseases. Considering OPN as a pro-inflammatory molecule, we hypothesize that the treatment with its neutralizing antibody (anti-OPN Ab) protects mice against intestinal I/R-induced acute lung injury (ALI). Intestinal I/R was induced in mice by superior mesenteric artery occlusion with a vascular clip. After 45 min of occlusion, the clip was removed and anti-OPN Ab (25 μg/mouse) or normal IgG isotype control (25 μg/mouse) was immediately administrated intravenously. Blood, small intestine, and lung tissues were collected at 4 h after reperfusion for various analyses. After intestinal I/R, mRNA and protein levels of OPN were significantly induced in the small intestine, lungs, and blood relative to sham-operated animals. Compared with the IgG control group, treatment of anti-OPN Ab significantly reduced plasma levels of pro-inflammatory cytokine and chemokine (IL-6 and MIP-2) and organ injury markers (AST, ALT, and LDH). The histological architecture of the gut and lung tissues in anti-OPN Ab-treated intestinal I/R-induced mice showed significant improvement versus the IgG control mice. The lung inflammation measured by the levels of IL-6, IL-1β, and MIP-2 was also significantly downregulated in the anti-OPN Ab-treated mice as compared with the IgG control mice. Besides, the lung MPO and neutrophil infiltration in anti-OPN Ab-treated mice showed significant reduction as compared with the IgG control animals. In conclusion, we have demonstrated beneficial outcomes of anti-OPN Ab treatment in protecting against ALI, implicating a novel therapeutic potential in intestinal I/R. PMID:26974422

  9. VDR Attenuates Acute Lung Injury by Blocking Ang-2-Tie-2 Pathway and Renin-Angiotensin System

    OpenAIRE

    Kong, Juan; Zhu, Xiangdong; Shi, Yongyan; Liu, Tianjing; Chen, Yunzi; Bhan, Ishir; Zhao, Qun; Thadhani, Ravi; Li, Yan Chun

    2013-01-01

    Acute lung injury (ALI) is a hallmark of systemic inflammation associated with high mortality. Although the vitamin D receptor (VDR) is highly expressed in the lung, its role in lung physiology remains unclear. We investigated the effect of VDR deletion on ALI using a lipopolysaccharide (LPS)-induced sepsis model. After LPS challenge VDR-null mice exhibited more severe ALI and higher mortality compared with wild-type (WT) counterparts, manifested by increased pulmonary vascular leakiness, pul...

  10. Pharyngeal oxygen administration increases the time to serious desaturation at intubation in acute lung injury: an experimental study

    OpenAIRE

    Engström, Joakim; Hedenstierna, Göran; Larsson, Anders

    2010-01-01

    Introduction Endotracheal intubation in critically ill patients is associated with severe life-threatening complications in about 20%, mainly due to hypoxemia. We hypothesized that apneic oxygenation via a pharyngeal catheter during the endotracheal intubation procedure would prevent or increase the time to life-threatening hypoxemia and tested this hypothesis in an acute lung injury animal model. Methods Eight anesthetized piglets with collapse-prone lungs induced by lung lavage were ventila...

  11. Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung

    OpenAIRE

    Zhang, Xuefeng; Jiang, Susan; Yu, Jinlong; Kuzontkoski, Paula M; Groopman, Jerome E

    2015-01-01

    Pulmonary complications are common in both AIDS patients and cocaine users. We addressed the cellular and molecular mechanisms by which HIV and cocaine may partner to induce their deleterious effects. Using primary lung lymphatic endothelial cells (L-LECs), we examined how cocaine and HIV-1 gp120, alone and together, modulate signaling and functional properties of L-LECs. We found that brief cocaine exposure activated paxillin and induced cytoskeletal rearrangement, while sustained exposure i...

  12. 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.

  13. Symptoms of epilepsy and organic brain dysfunctions in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

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    Linaker Olav M

    2009-09-01

    Full Text Available Abstract Background In psychiatric acute departments some patients present with brief depressive periods accompanied with fluctuating arrays of other psychiatric symptoms like psychosis, panic or mania. For the purpose of the present study we call this condition Acute Unstable Depressive Syndrome (AUDS. The aims of the present study were to compare clinical signs of organic brain dysfunctions and epilepsy in patients with AUDS and Major Depressive Episode (MDE. Methods Out of 1038 consecutive patients admitted to a psychiatric acute ward, 16 patients with AUDS and 16 age- and gender-matched MDE patients were included in the study. Using standardized instruments and methods we recorded clinical data, EEG and MRI. Results A history of epileptic seizures and pathologic EEG activity was more common in the AUDS group than in the MDE group (seizures, n = 6 vs. 0, p = 0.018; pathologic EEG activity, n = 8 vs. 1, p = 0.015. Five patients in the AUDS group were diagnosed as having epilepsy, whereas none of those with MDE had epilepsy (p = 0.043. There were no differences between the groups regarding pathological findings in neurological bedside examination and cerebral MRI investigation. Conclusion Compared to patients admitted with mood symptoms fulfilling DSM 4 criteria of a major depressive disorder, short-lasting atypical depressive symptoms seem to be associated with a high frequency of epileptic and pathologic EEG activity in patients admitted to psychiatric acute departments. Trial registration NCT00201474

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

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    Stan Ryniak

    2014-01-01

    Full Text Available A 16-year-old woman with craniofacial injury developed severe acute respiratory failure under the primary reconstructive surgical procedure requiring several units of blood and plasma. A transfusion related acute lung injury (TRALI was suspected and supportive treatment was initiated. Because of the severity of symptoms, acute extracorporeal membrane oxygenation (ECMO was planned. During preparation for ECMO, a single intravenous dose, 1 g of tranexamic acid, was administered and a remarkable improvement was observed shortly thereafter. The patient was placed on ECMO for 16 hours. The further course was uncomplicated and the patient was discharged from ICU on the 6th day after admission fully and she recovered. A clinical improvement was observed in a timely fashion following the administration of tranexamic acid. The handling of a suspected TRALI and potential benefit from administration of tranexamic acid are discussed in this case report.

  15. Acute nicotine treatment attenuates lipopolysaccharide-induced cognitive dysfunction by increasing BDNF expression and inhibiting neuroinflammation in the rat hippocampus.

    Science.gov (United States)

    Wei, Penghui; Liu, Qingshen; Li, Dong; Zheng, Qiang; Zhou, Jinfeng; Li, Jianjun

    2015-09-14

    Although nicotine has been shown to improve cognitive function in various studies, the mechanisms underlying acute nicotine treatment-induced neuroprotection remain incompletely understood. In this study, we evaluated the effect of acute nicotine treatment on the cognitive impairment induced by lipopolysaccharide (LPS) and explored the underlying mechanism. We found that acute nicotine injection markedly attenuated LPS-elicited cognitive deficits and suppressed the strong LPS-induced release of IL-1β, IL-6, and TNF-α into serum and the dorsal hippocampus at 4 and 24h after LPS injection. Western blot analysis indicated a clear increase in the levels of cleaved caspase-3 in LPS-treated animals but not in nicotine- or saline-treated animals. Furthermore, nicotine administration led to a significant increase in BDNF mRNA expression at 4 and 24h and in BDNF protein expression at 24h after LPS injection in the dorsal hippocampus. Taken together, acute nicotine administration attenuated LPS-induced cognitive dysfunction, and this neuroprotective effect may be related to the up-regulation of BDNF and the inhibition of neuroinflammation and apoptosis-related proteins in the dorsal hippocampus. PMID:26259694

  16. Widening of coronary sinus in CT pulmonary angiography indicates right ventricular dysfunction in patients with acute pulmonary embolism

    International Nuclear Information System (INIS)

    Right ventricular dysfunction (RVD) may occur in the course of acute pulmonary embolism (PE). Patients with RVD need more intensive treatment, and the prognosis is more severe. The aim of this study was to evaluate the usefulness of the measurement of the coronary sinus in the assessment of RVD in patients with acute PE and to compare it with other indicators of RVD. Retrospective assessment of 55 CT pulmonary angiography examinations with signs of acute PE was performed. Pulmonary artery systolic pressure (PASP) was echocardiographically assessed in all patients, and RVD was defined as PASP values greater than 30 mmHg. CT measurements included the size of the heart ventricles, mediastinal vessels and the width of the coronary sinus. Median width of the coronary sinus was 16 mm (range 12-24 mm) in patients with increased PASP and 10 mm (range 7-22 mm) in patients with normal PASP (p = 0.001). Best cut-off value was assessed to be 12.5 mm, with sensitivity 94% and specificity 75%. It was characterised by the largest area under ROC curve (0.82) among analysed parameters. Width of the coronary sinus seems to be a promising parameter for identification of RVD in patients with acute PE. A prospective study should be undertaken to further assess its clinical and prognostic applicability. (orig.)

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

    Science.gov (United States)

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

  18. Effects of continuous tracheal gas insufflation during pressure limited ventilation on pulmonary surfactant in rabbits with acute lung injury

    Institute of Scientific and Technical Information of China (English)

    ZHU Guang-fa; ZHANG Wei; ZONG Hua; LIANG Ying

    2006-01-01

    Background Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (VT) while maintaining constant partial arterial CO2 pressure (PaCO2). We hypothesised that TGI limited peak inspiratory pressure (PIP) and VT and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI).Methods ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n=8 for each group), and subsequently ventilated with limited PIP and VT to maintain PaCO2 within 35 to 45 mmHg for 4 hours. Physiological dead space to VT ratio (VD/VT), dynamic respiratory compliance (Cdyn) and partial arterial O2 pressure (PaO2) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (Vv), myeloperoxidase and interleukin (IL)-8.Results TGI resulted in significant (P<0.05 or P<0.01) decrease in PIP [(22.4±1.8) cmH2O vs (29.5±1.1) cmH2O], VT [(6.9±1.3) ml/kg vs (9.8±1.11) ml/kg], VD/VT [(32±5)% vs (46±2)%], TP [(109±22) mg/kg vs (187±25) mg/kg], SA/LA (2.5±0.4 vs 5.4±0.7), myeloperoxidase [(6.2±0.5) U/g tissue vs (12.3±0.8) U/g tissue] and IL-8 [(987±106) ng/g tissue vs (24±3) mN/m] of BALF, and significant (P<0.05) increase in Cdyn [(0.47±0.02) ml ·cmH2O-1 ·kg-1 vs (0.31±0.02) ml ·cmH2O-1 ·kg-1], PaO2 [(175±24) mmHg vs (135±26) mmHg],TPL/TP (52±8 vs 33±11) and Vv (0.65±0.05 vs 0

  19. EFFECT OF LEFT VENTRICULAR SYSTOLIC DYSFUNCTION ON CEREBRAL HEMODYNAMICS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION (THE RESULTS OF OBSERVATIONAL STUDIES

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    V. E. Kulikov

    2015-12-01

    Full Text Available Aim. To study the effect of left ventricular (LV systolic dysfunction on cerebral hemodynamic in patients with ST segment elevation myocardial infarction (STEMI during acute period. Material and methods. Cerebral hemodynamics ultrasound assessment was performed in the extra-and intracranial vessels in 118 patients with STEMI. Results. Significant changes in cerebral hemodynamics were found in LV systolic dysfunction with ejection fraction (LVEF ≤40% due to hemispheric blood flow asymmetry in the middle cerebral artery (MCA as large as 45.1±6.7% with correlation coefficient r=-0.87. Compensation of cerebral blood flow was manifested in vasoconstriction or vasodilation (resistive index 0.63-0.76 and 0.49-0.43 c.u., respectively. Conclusion. A strong relationship between LV systolic dysfunction and cerebral hemodynamic was found in patients with STEMI. It was manifested in significant contralateral hemispheric blood flow asymmetry in MCA in patients with LVEF ≤40%. Reduction in cerebral blood flow velocity activated autoregulation mechanism in the form of vasoconstriction or vasodilation.

  20. Logistic regression model for identification of right ventricular dysfunction in patients with acute pulmonary embolism by means of computed tomography

    International Nuclear Information System (INIS)

    Purpose: Diagnosis of right ventricular dysfunction in patients with acute pulmonary embolism (PE) is known to be associated with increased risk of mortality. The aim of the study was to calculate a logistic regression model for reliable identification of right ventricular dysfunction (RVD) in patients diagnosed with computed tomography pulmonary angiography. Material and methods: Ninety-seven consecutive patients with acute pulmonary embolism were divided into groups with and without RVD basing upon echocardiographic measurement of pulmonary artery systolic pressure (PASP). PE severity was graded with the pulmonary obstruction score. CT measurements of heart chambers and mediastinal vessels were performed; position of interventricular septum and presence of contrast reflux into the inferior vena cava were also recorded. The logistic regression model was prepared by means of stepwise logistic regression. Results: Among the used parameters, the final model consisted of pulmonary obstruction score, short axis diameter of right ventricle and diameter of inferior vena cava. The calculated model is characterized by 79% sensitivity and 81% specificity, and its performance was significantly better than single CT-based measurements. Conclusion: Logistic regression model identifies RVD significantly better, than single CT-based measurements

  1. Bedside lung ultrasound in the evaluation of acute decompensated heart failure.

    Science.gov (United States)

    Leidi, Federica; Casella, Francesco; Cogliati, Chiara

    2016-06-01

    Dyspnea is a common presenting complaint in the emergency department (ED) and a leading cause of hospitalization in intensive care unit (ICU) and medical wards. Ultrasound (US) has traditionally been considered inadequate to explore the aerated lung. However, in the past 15 years LUS gained broader application, at least in part thanks to the interpretation of the artefacts generated by the interaction of US and lung structures/content. The total reflection of US beam occurring at the pleural level determines the artefactual image of the aerated lung: an homogenous 'foggy-like' picture under the pleural line. As the air content of the lungs decreases due to interstitial imbibition, deposition of collagen or presence of blood, vertical artefacts -arising from the pleural line and moving synchronously with the respiration- called B-lines appear. Multiple and bilateral B-lines identify the alveolar-interstitial syndrome (AIS). The most common cause of AIS is the wet lung: the more the congestion burden, the more the extent of the B-lines, which become confluent until the so-called white lung in case of pulmonary edema. Many studies showed a higher accuracy of LUS in diagnosing acute decompensated heart failure (ADHF) as compared to chest X-ray As recently shown, the integration of LUS to clinical assessment allow to differentiate cardiogenic dyspnea with sensitivity and specificity greater than 95 %. Moreover, LUS can easily detect pleural effusion -frequently present in ADHF-appearing as an anechoic area in the recumbent area of the thorax, delimited inferiorly by the diaphragmatic dome and superiorly by the aerated lung. PMID:26885846

  2. Enhanced Hsp70 expression protects against acute lung injury by modulating apoptotic pathways.

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    Gabriella Aschkenasy

    Full Text Available The Acute respiratory distress syndrome (ARDS is a highly lethal inflammatory lung disorder. Apoptosis plays a key role in its pathogenesis. We showed that an adenovirus expressing the 70 kDa heat shock protein Hsp70 (AdHSP protected against sepsis-induced lung injury. In this study we tested the hypothesis that AdHSP attenuates apoptosis in sepsis-induced lung injury. Sepsis was induced in rats via cecal ligation and double puncture (2CLP. At the time of 2CLP PBS, AdHSP or AdGFP (an adenoviral vector expressing green fluorescent protein were injected into the tracheas of septic rats. 48 hours later, lungs were isolated. One lung was fixed for TUNEL staining and immunohistochemistry. The other was homogenized to isolate cytosolic and nuclear protein. Immunoblotting, gel filtration and co-immunoprecipitation were performed in these extracts. In separate experiments MLE-12 cells were incubated with medium, AdHSP or AdGFP. Cells were stimulated with TNFα. Cytosolic and nuclear proteins were isolated. These were subjected to immunoblotting, co-immunoprecipitation and a caspase-3 activity assay. TUNEL assay demonstrated that AdHSP reduced alveolar cell apoptosis. This was confirmed by immunohistochemical detection of caspase 3 abundance. In lung isolated from septic animals, immunoblotting, co-immunoprecipitation and gel filtration studies revealed an increase in cytoplasmic complexes containing caspases 3, 8 and 9. AdHSP disrupted these complexes. We propose that Hsp70 impairs apoptotic cellular pathways via interactions with caspases. Disruption of large complexes resulted in stabilization of lower molecular weight complexes, thereby, reducing nuclear caspase-3. Prevention of apoptosis in lung injury may preserve alveolar cells and aid in recovery.

  3. Sphingomyelin synthase 2 affects CD14‑associated induction of NF‑κB by lipopolysaccharides in acute lung injury in mice.

    Science.gov (United States)

    Hu, Shidong; Ding, Yi; Gong, Jie; Yan, Nianlong

    2016-10-01

    Lipopolysaccharide (LPS) is the predominant component of the outer membrane of Gram-negative bacteria, which can cause severe inflammation in the body. The acute lung injury (ALI) induced by LPS can cause extensive damage to the lung tissue, the severe stage of which is termed acute respiratory distress syndrome, when multiple organ dysfunction syndrome may appear. There are no effective clinical treatment measures at present. The involvement of cluster of differentiation (CD)14 assists LPS in causing inflammatory reactions, and CD14 and sphingomyelin (SM), located in lipid rafts areas, are closely associated. SM synthase (SMS) is a key enzyme in the synthesis of SM, however, the effect of SMS on the inflammatory pathway involving nuclear factor (NF)‑κB induced by LPS remains to be elucidated. Under the premise of the establishment of an ALI mouse model induced by LPS, the present study established a control group, LPS group and pyrrolidine dithiocarbamate (PDTC; an NF‑κB pathway inhibitor) group. Hematoxylin‑eosin staining, reverse transcription‑quantitative polymerase chain reaction analysis, western blot analysis and thin layer chromatography were used to investigate the mechanism of SMS in ALI. Compared with the control group, the mRNA and protein levels of CD14 were significantly increased (P<0.001; n=5 and P<0.05, n=5), and the activity of SMS and expression of SMS2 were significantly upregulated (P<0.001; n=5 and P<0.05, n=5) in the model group. The increases of SMS2 and CD14 in the PDTC group were less marked, compared with those in the model group (P<0.05; n=5). These findings suggested that the degree of lung injury was reduced during the acute inflammatory reaction when NF‑κB was inhibited, and that the expression of SMS2 may affect the induction of the NF‑κB pathway by LPS through CD14. PMID:27510408

  4. Neutrophil DNA contributes to the antielastase barrier during acute lung inflammation.

    Science.gov (United States)

    Balloy, Viviane; Sallenave, Jean-Michel; Crestani, Bruno; Dehoux, Monique; Chignard, Michel

    2003-06-01

    During acute lung inflammation, the airspaces are invaded by circulating neutrophils. These may then injure tissues through the release of elastase. Different natural specific inhibitors such as alpha1-proteinase inhibitor, secretory leukocyte proteinase inhibitor, and elafin are nonetheless able to counteract the enzymatic activity of elastase. The present study was undertaken to assess the role of these different inhibitors in the intrinsic antielastase barrier during lipopolysaccharide-induced lung inflammation in mice. Upon intranasal administration of lipopolysaccharide to mice, the antielastase activity recovered from bronchoalveolar lavage fluids (BALF) increases progressively up to 48 h (7-fold) and returns to the basal level within 72 h. By contrast, when the same experiments are performed with neutropenic mice (pretreatment with an antigranulocyte antibody, or vinblastine), the increase is almost totally absent. Ultrafiltration of BALF through 100 kD cutoff membranes shows that the activity remains in the retentate, thus ruling out a role for native alpha1-proteinase inhibitor, secretory leukocyte proteinase inhibitor, and elafin. Gel filtration and fraction analysis show that the material eluted with a Mr of 600 kD. Agarose gel electrophoresis and ethidium bromide staining reveal that the activity corresponds to the presence a large amount of DNA. Interestingly, DNase treatment of the active fraction suppresses the antielastase activity. Analysis of BALF from patients with acute lung inflammation shows the presence of DNA with antielastase activity. We therefore concluded that during acute lung inflammation, the recruitment of neutrophils in the airspaces accounts for the increased presence of DNA, which in turn contributes to the antielastase barrier. PMID:12600833

  5. 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.

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

    OpenAIRE

    Abdulzahra Hussain; Shamsi El-Hasani; Ali Adnan

    2012-01-01

    Context Small cell carcinoma of the lung is an aggressive cancer with gloomy prognosis. Links to acute pancreatitis is extremely rare. Case report We are reporting a 53-year-old patient who was admitted because of acute pancreatitis. She had no history of gallstones, alcohol abuse, medications or any other predisposition for acute pancreatitis. Further investigations of blood, CT of chest abdomen and neck and ultrasound scan of abdomen, bone marrow and neck lymph node biopsies confirmed advan...

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

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    Xiaomei Feng

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

  8. 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.

  9. 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.

  10. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1.

    OpenAIRE

    Mei, Shirley H. J; McCarter, Sarah D.; Yupu Deng; Parker, Colleen H; Conrad Liles, W.; Duncan J Stewart

    2007-01-01

    Editors' Summary Background. Critically ill people who have had an injury to their lungs, for example through pneumonia, trauma, or an immune response to infection, may end up developing a serious complication in the lung termed acute respiratory distress syndrome (ARDS). In ARDS, inflammation develops in the lung, and fluid builds up in the alveoli (the air sacs resembling “bunches of grapes” at the ends of the network of tubes in the lung). This buildup of fluid prevents oxygen from being c...

  11. 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

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

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    Daniely Cornélio Favarin

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    张雪哲; 王武; 卢延; 黄振国; 洪闻; 尚燕宁; 任安

    2003-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  15. 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.

  16. 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.

  17. Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation

    Directory of Open Access Journals (Sweden)

    Silvie Kremserova

    2016-01-01

    Full Text Available Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO, abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site.

  18. Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation.

    Science.gov (United States)

    Kremserova, Silvie; Perecko, Tomas; Soucek, Karel; Klinke, Anna; Baldus, Stephan; Eiserich, Jason P; Kubala, Lukas

    2016-01-01

    Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO), abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site. PMID:26998194

  19. 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. PMID:26276127

  20. Mitochondrial dysfunction and transactivation of p53-dependent apoptotic genes in BaP-treated human fetal lung fibroblasts.

    Science.gov (United States)

    Yang, Guangtao; Jiang, Ying; Rao, Kaimin; Chen, Xi; Wang, Qian; Liu, Ailin; Xiong, Wei; Yuan, Jing

    2011-12-01

    Benzo(a)pyrene (BaP) has been shown to be an inducer of apoptosis. However, mechanisms involved in BaP-induced mitochondrial dysfunction are not well-known. In this study, human fetal lung fibroblasts cells were treated with BaP (8, 16, 32, 64 and 128 μM) for 4 and 12 h. Cell viability, intracellular level of reactive oxygen species (ROS), total antioxidant capacity (T-AOC), mitochondrial membrane potential (ΔΨ(m)) and cytochrome c release were determined. Changes in transcriptional levels of p53-dependent apoptotic genes (p53, APAF1, CASPASE3, CASPASE9, NOXA and PUMA) were measured. At time point of 4 h, BaP induced the intracellular ROS generation in 64 (p BaP groups (p BaP groups (p BaP groups (p BaP group (p BaP groups (p BaP group a relatively little expression of p53 mRNA was observed (p BaP promoted the generation of excessive ROS and subsequently the mitochondrial depolarization, whereas transactivations of the p53-dependent apoptotic genes were significantly induced at the later period.

  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. PMID:24577726

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

    OpenAIRE

    Hartog, Anneke; Vazquez de Anda, G.F.; Gommers, Diederik; Kaisers, U; Verbrugge, Serge; Schnabel, R.; 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 rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value < 13 kPa. Animals were then allocated randomly (n = 12 in eac...

  3. 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.

  4. Acute kidney injury is common, parallels organ dysfunction or failure, and carries appreciable mortality in patients with major burns: a prospective exploratory cohort study

    OpenAIRE

    Steinvall, Ingrid; Bak, Zoltan; Sjöberg, Folke

    2008-01-01

    Introduction: The purpose of this study was to determine the incidence, time course, and outcome of acute kidney injury after major burns and to evaluate the impact of possible predisposing factors ( age, gender, and depth and extent of injury) and the relation to other dysfunctioning organs and sepsis. Method: We performed an explorative cohort study on patients with a TBSA% (percentage burned of total body surface area) of 20% or more who were admitted to a national burn centre. Acute kidne...

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  6. Multi-detector CT/CT angiogram assessment of acute pancreatic graft dysfunction

    International Nuclear Information System (INIS)

    Simultaneous pancreatic-kidney transplantation is the definitive treatment for patients with type 1 diabetes mellitus and renal failure. Pancreatic graft failure is an important postoperative complication and most commonly occurs as a result of pancreatitis, graft thrombosis or rejection. Distinguishing between these causes is necessary to determine timely, appropriate management and thereby potentially minimising graft loss. Multi-detector CT imaging may be used to identify the cause of pancreatic graft dysfunction when renal function is not markedly impaired.

  7. Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome)

    OpenAIRE

    Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Ítalo Bruno dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

    2013-01-01

    Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concen...

  8. Acute Lung Injury Induced by Lipopolysaccharide Is Independent of Complement Activation1

    OpenAIRE

    Rittirsch, Daniel; Flierl, Michael A; Day, Danielle E.; Nadeau, Brian A.; McGuire, Stephanie R.; Hoesel, Laszlo M.; Ipaktchi, Kyros; Zetoune, Firas S.; Sarma, J. Vidya; Leng, Lin; Huber-Lang, Markus S.; Neff, Thomas A.; Bucala, Richard; Ward, Peter A.

    2008-01-01

    Although acute lung injury (ALI) is an important problem in humans, its pathogenesis is poorly understood. Airway instillation of bacterial LPS, a known complement activator, represents a frequently used model of ALI. In the present study, pathways in the immunopathogenesis of ALI were evaluated. ALI was induced in wild-type, C3–/–, and C5–/– mice by airway deposition of LPS. To assess the relevant inflammatory mediators, bronchoalveolar lavage fluids were evaluated by ELISA analyses and vari...

  9. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Wang Cairui; Zhou Guopeng; Zeng Zeng

    2014-01-01

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

  11. Acute endotoxemia is associated with upregulation of lipocalin 24p3/Lcn2 in lung and liver

    OpenAIRE

    Sunil, Vasanthi R.; Patel, Kinal J.; Nilsen-Hamilton, Marit; Heck, Diane E.; Laskin, Jeffrey D.; Laskin, Debra L.

    2007-01-01

    Acute endotoxemia is associated with production of acute phase proteins which regulate inflammatory responses to tissue injury. Consistent with DNA microarray experiments, we found that acute endotoxemia, induced by administration of lipopolysaccharide (LPS) to mice (1 mg/kg) or rats (5 mg/kg), resulted in increased expression of the hepatic acute phase protein, lipocalin 24p3, which was evident within 4 h and persisted for 24–48 h. Increases in 24p3 expression were also observed in the lung ...

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

    Science.gov (United States)

    Grabiec, Aleksander M; Hussell, Tracy

    2016-07-01

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

  13. Relationship between glucose fluctuation and the degree of nervous dysfunction of the acute cerebral infarction in patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    张名扬

    2014-01-01

    Objective To investigate the relationship between glucose fluctuation and the degree of nervous dysfunction of the acute cerebral infarction in patients with type 2 diabetes mellitus.Methods 30 patients with ACI and T2DM were chosen as observation group and 30 patients with T2DM without ACI as the control group.Glucose

  14. Amiodarone use after acute myocardial infarction complicated by heart failure and/or left ventricular dysfunction may be associated with excess mortality

    DEFF Research Database (Denmark)

    Thomas, Kevin L; Al-Khatib, Sana M; Lokhnygina, Yuliya;

    2008-01-01

    BACKGROUND: We sought to assess the association of amiodarone use with mortality during consecutive periods in patients with post-acute myocardial infarction with left ventricular systolic dysfunction and/or HF treated with a contemporary medical regimen. METHODS: This study used data from VALIAN...

  15. Is echocardiography a valid tool to screen for left ventricular systolic dysfunction in chronic survivors of acute myocardial infarction? A comparison with radionuclide ventriculography

    OpenAIRE

    Galasko, G I W; S. Basu; Lahiri, A; Senior, R

    2004-01-01

    Objective: To assess the accuracy of echocardiography with Simpson’s apical biplane method in screening for left ventricular systolic dysfunction (LVSD) in patients six months after acute myocardial infarction (AMI) as compared with radionuclide ventriculography by assessing the proportion of clinically significant errors that occur with echocardiography.

  16. Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group

    DEFF Research Database (Denmark)

    Gustafsson, I; Torp-Pedersen, C; Køber, L;

    1999-01-01

    OBJECTIVES: This study evaluated the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril in diabetic patients with left ventricular dysfunction after acute myocardial infarction (AMI). BACKGROUND: Patients with diabetes mellitus have a high mortality...

  17. The effects of aquaporins in different animal models of acute lung injury%水通道蛋白在不同急性肺损伤模型中的作用

    Institute of Scientific and Technical Information of China (English)

    刘溪; 尚嘉伟; 王爱忠

    2014-01-01

    Background Acute lung injury (ALI) is a common syndrome with high mortality and disability rate.The imbalance of water in lung plays a significant role in the complicated pathological mechanisms of ALI.Dysfunction of lung vascular endothelial cells were thought to be accounted for the high permeability,however,the discovery of aquaporins (AQP),brings a novel perspective into this field.Objective Know about aquaporins' functions in different animal models of ALI.Content we will review aquaporins' general features,distribution in the lung,and functions in different animal models of acute lung injury.Trend Explore functions of aquaporins in the pathological mechanism of ALI,providing new thoughts for clinical treatments.%背景 急性肺损伤(acute lung injury,ALI)是临床上常见的急重病症,致残率和致死率均极高.肺损伤时肺水平衡失调是其病理过程中十分重要的一环,以往人们对其原因的认识仅仅停留于肺毛细血管内皮细胞损伤而引起的通透性增加,如今,水通道蛋白(aquaporin,AQP)的发现及其研究的深入为ALI肺水肿的机制带来了新的视角. 目的 了解AQP在不同诱因导致的ALI病理过程中的作用. 内容 AQP的一般特性、在肺组织中的分布及AQP在不同ALI模型中的作用. 趋势 探索AQP在ALI病理过程中的作用,为临床上治疗ALI提供新的思路.

  18. 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.

  19. Microvascular dysfunction is associated with plasma osteoprotegerin levels in patients with acute myocardial infarction

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B;

    2013-01-01

    Osteoprotegerin (OPG) is a glycoprotein that inhibits nuclear factor-κB's regulatory effects on inflammation, skeletal, and vascular systems, and is a potential biomarker of atherosclerosis and seems to be involved in vascular calcifications. The objective of this study was to assess the relation...... relationship between OPG, left ventricular function, and microvascular function in patients with acute myocardial infarction (AMI)....

  20. Comparative analysis between the alveolar recruitment maneuver and breath stacking technique in patients with acute lung injury

    OpenAIRE

    Porto, Elias Ferreira; Tavolaro, Kelly Cristiani; Kumpel, Claudia; Oliveira, Fernanda Augusta; Sousa, Juciaria Ferreira; de Carvalho, Graciele Vieira; de Castro, Antonio Adolfo Mattos

    2014-01-01

    Objective To compare the effectiveness of the alveolar recruitment maneuver and the breath stacking technique with respect to lung mechanics and gas exchange in patients with acute lung injury. Methods Thirty patients were distributed into two groups: Group 1 - breath stacking; and Group 2 - alveolar recruitment maneuver. After undergoing conventional physical therapy, all patients received both treatments with an interval of 1 day between them. In the first group, the breath stacking techniq...

  1. LPS-Induced Lung Inflammation in Marmoset Monkeys – An Acute Model for Anti-Inflammatory Drug Testing

    OpenAIRE

    Sophie Seehase; Hans-Dieter Lauenstein; Christina Schlumbohm; Simone Switalla; Vanessa Neuhaus; Christine Förster; Hans-Gerd Fieguth; Olaf Pfennig; Eberhard Fuchs; Franz-Josef Kaup; Martina Bleyer; Hohlfeld, Jens M.; Armin Braun; Katherina Sewald; Sascha Knauf

    2012-01-01

    Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS)-induced inflammation model was established in marmoset monkeys (Callithrix jacchus) to reflect crucial features of inflammatory lung diseases. Firstly, in ...

  2. Constrictive pericarditis after lung transplantation: an under-recognized complication.

    Science.gov (United States)

    Karolak, Wojtek; Cypel, Marcelo; Chen, Fengshi; Daniel, Lorretta; Chaparro, Cecilia; Keshavjee, Shaf

    2010-05-01

    Primary graft dysfunction, acute rejection, and infection account for most of the early morbidity after lung transplantation, with bronchiolitis obliterans syndrome accounting for most late morbidity. Mediastinal and pericardial complications, in the form of constriction, are not common. We present 4 patients with constrictive pericarditis after lung transplantation and recommend that constrictive pericarditis be considered in the differential diagnosis in lung transplant recipients who present with signs and symptoms of systemic and pulmonary venous congestion. PMID:20207169

  3. Computed tomography densitometry of the lung: a method to assess perfusion defects in acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Groell, Reinhard E-mail: reinhard.groell@kfunigraz.ac.at; Peichel, Karl H.; Uggowitzer, Martin M.; Schmid, Ferdinand; Hartwagner, Karin

    1999-12-01

    Objective: To evaluate the potential of spiral computed tomography (CT) densitometry of the lung to assess segmental perfusion defects in patients with acute pulmonary embolism. Materials and Methods: Ten patients with known segmental or lobar perfusion defects on ventilation/perfusion scintigraphy and with normal findings in the contralateral lung segment underwent spiral CT of the thorax before and after the administration of contrast material. Regions of interest were defined in 14 segments with normal perfusion and in 14 segments with reduced perfusion. Three consecutive densitometry measurements were performed in each segment. Results: Those segments with reduced perfusion showed a significantly lower mean CT value on the enhanced scans (-813.4{+-}57.1 Hounsfield units (HU) vs -794.0{+-}44.8 HU, P=0.01) and a significantly decreased contrast enhancement (12.3{+-}18.2 HU vs 29.8{+-}16.6 HU, P<0.01) when compared to segments with normal perfusion. Measurements from the unenhanced CT scans were not statistically different between segments with reduced and normal perfusion. Conclusions: Spiral CT densitometry allows the assessment of at least segmental perfusion defects in patients with acute pulmonary embolism.

  4. The functional comorbidity index had high inter-rater reliability in patients with acute lung injury

    Directory of Open Access Journals (Sweden)

    Fan Eddy

    2012-09-01

    Full Text Available Abstract Background The Functional Comorbidity Index (FCI was recently developed to predict physical function in acute lung injury patients using comorbidity data. Our objectives were to determine: (1 the inter-rater reliability of the FCI collected using in-patient discharge summaries (primary objective; and (2 the accuracy and predictive validity of the FCI collected using hospital discharge summaries and admission records versus complete chart review (secondary objectives. Methods For reliability, we evaluated the FCI’s intraclass correlation coefficient (ICC among trained research staff performing data collection for 421 acute lung injury patients enrolled in a prospective cohort study. For validity and accuracy, we compared the detection of FCI comorbidities across three types of inpatient medical records, and the association of the respective FCI scores obtained with patients’ SF-36 physical function subscale (PFS scores at 1-year follow-up. Results Inter-rater reliability was near-perfect (ICC 0.91; 95% CI 0.89-0.94. Hospital admission records and discharge summaries (vs. complete chart review significantly underestimated the total FCI score. However, using multivariable linear regression, FCI scores collected using each of the three types of inpatient medical records had similar associations with PFS, suggesting similar predictive value. Conclusions Data collection using in-patient discharge summaries represents a reliable and valid method for collecting FCI comorbidity information.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  6. Lung Postmortem Autopsy Revealing Extramedullary Involvement in Multiple Myeloma Causing Acute Respiratory Distress Syndrome

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    Aurélie Ravinet

    2014-01-01

    Full Text Available Pulmonary involvement with multiple myeloma is rare. We report the case of a 61-year-old man with past medical history of chronic respiratory failure with emphysema, and a known multiple myeloma (Durie and Salmon stage III B and t(4;14 translocation. Six months after diagnosis and first line of treatment, he presented acute dyspnea with interstitial lung disease. Computed tomography showed severe bullous emphysema and diffuse, patchy, multifocal infiltrations bilaterally with nodular character, small bilateral pleural effusions, mediastinal lymphadenopathy, and a known lytic lesion of the 12th vertebra. He was treated with piperacillin-tazobactam, amikacin, oseltamivir, and methylprednisolone. Finally, outcome was unfavourable. Postmortem analysis revealed diffuse and nodular infracentimetric infiltration of the lung parenchyma by neoplastic plasma cells. Physicians should be aware that acute respiratory distress syndrome not responding to treatment of common causes could be a manifestation of the disease, even with negative BAL or biopsy and could be promptly treated with salvage therapy.

  7. Gastric pH and motility in a porcine model of acute lung injury using a wireless motility capsule

    OpenAIRE

    Rauch, Stefan; Muellenbach, Ralf M.; Johannes, Amélie; Zollhöfer, Bernd; Roewer, Norbert

    2011-01-01

    Summary Background Evaluation of gastric pH and motility in a porcine model of acute lung injury using a novel, wireless motility capsule. Material/Methods A motility capsule was applied into the stomach of 7 Pietrain pigs with acute lung injury induced by high volume saline lavage. Wireless transmission of pH, pressure and temperature data was performed by a recorder attached to the animal’s abdomen. Gastric motility was evaluated using pH and pressure values, and capsule location was confir...

  8. Overall and regional lung function in dogs exposed acutely to ozone

    International Nuclear Information System (INIS)

    Regional distribution of ventilation and overall function of the lungs were compared in anesthetized, paralyzed, mechanically ventilated dogs exposed to ozone. Three animals were exposed at each concentration (0. 0.13, 0.22, and 0.45 ppm ozone ) for 3 hr. There were no significant changes in pulmonary flow resistance, dynamic compliance, or flow rates derived from maximum forced expiratory maneuvers. The distribution of inspired gas was determined using air containing 13N and a positron camera to follow wash-in in each of 80 or more regions of the lung. The mean wash in time (T) and its standard deviation did not change in sham-treated dogs, but T increased by 40 to 100% in exposed animals. Dogs showing increases in T also had increased frequency dependence of compliance. The changes in 13N wash-in reflected less uniform distribution of ventilation, with the greatest disparity occurring between central and marginal regions. Altered regional mechanical function, in the absence of overall changes, suggested that the initial effect of ozone was on the small airways. The measurement may be a sensitive indicator of acute irritation in the lung periphery

  9. Derecruitment Test and Surfactant Therapy in Patients with Acute Lung Injury

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    Alexey A. Smetkin

    2012-01-01

    Full Text Available Introduction. A recruitment maneuver (RM may improve gas exchange in acute lung injury (ALI. The aim of our study was to assess the predictive value of a derecruitment test in relation to RM and to evaluate the efficacy of RM combined with surfactant instillation in patients with ALI. Materials and Methods. Thirteen adult mechanically ventilated patients with ALI were enrolled into a prospective pilot study. The patients received protective ventilation and underwent RM followed by a derecruitment test. After a repeat RM, bovine surfactant (surfactant group, n=6 or vehicle only (conventional therapy group, n=7 was instilled endobronchially. We registered respiratory and hemodynamic parameters, including extravascular lung water index (EVLWI. Results. The derecruitment test decreased the oxygenation in 62% of the patients. We found no significant correlation between the responses to the RM and to the derecruitment tests. The baseline EVLWI correlated with changes in SpO2 following the derecruitment test. The surfactant did not affect gas exchange and lung mechanics but increased EVLWI at 24 and 32 hrs. Conclusions. Our study demonstrated no predictive value of the derecruitment test regarding the effects of RM. Surfactant instillation was not superior to conventional therapy and might even promote pulmonary edema in ALI.

  10. Recruitment maneuver: RAMP versus CPAP pressure profile in a model of acute lung injury.

    Science.gov (United States)

    Riva, D R; Contador, R S; Baez-Garcia, C S N; Xisto, D G; Cagido, V R; Martini, S V; Morales, M M; Rocco, P R M; Faffe, D S; Zin, W A

    2009-10-31

    We examined whether recruitment maneuvers (RMs) with gradual increase in airway pressure (RAMP) provide better outcome than continuous positive airway pressure (CPAP) in paraquat-induced acute lung injury (ALI). Wistar rats received saline intraperitoneally (0.5 mL, CTRL) or paraquat (15 mg/kg, ALI). Twenty-four hours later lung mechanics [static elastance, viscoelastic component of elastance, resistive, viscoelastic and total pressures] were determined before and after recruitment with 40cmH2O CPAP for 40s or 40-s-long slow increase in pressure up to 40cmH2O (RAMP) followed by 0 or 5 cmH2O PEEP. Fractional area of alveolar collapse and PCIII mRNA were determined. All mechanical parameters and the fraction area of alveolar collapse were higher in ALI compared to CTRL. Only RAMP-PEEP maneuver significantly improved lung mechanics and decreased PCIII mRNA expression (53%) compared with ALI, while both RMs followed by PEEP decreased alveolar collapse. In conclusion, in the present experimental ALI model, RAMP followed by 5cm H2O PEEP yields a better outcome. PMID:19712760

  11. Pulmonary clearance of radiotracers after positive end-expiratory pressure or acute lung injury

    International Nuclear Information System (INIS)

    In anesthetized rabbits we measured clearance from lung to blood of eight aerosolized technetium-99m-labeled compounds: diethylenetriaminepentaacetate (99mTc-DTPA); cytochrome c; myoglobin; a myoglobin polymer; albumin; and anionic, cationic, and neutral dextrans of equivalent molecular size. We investigated the effect of applying positive end-expiratory pressure (PEEP) and, on a subsequent occasion, of injecting oleic acid intravenously to produce acute lung injury on the pulmonary clearance rate. Base-line clearance rates were monoexponential and varied with the molecular weights of the radiotracers. For each tracer the rate of clearance was increased a similar degree by either PEEP or oleic acid. However, with PEEP, clearance remained monoexponential, whereas after oleic acid, smaller molecular-weight radiotracers had multiexponential clearance curves. This suggests that after oleic acid the alveolar epithelium breaks down in a nonuniform fashion. We conclude that differentiation of the effect of PEEP from that of severe lung injury caused by oleic acid is not readily accomplished by either increasing the size of the tracer molecule or by varying the molecular charge

  12. Eupatorium lindleyanum DC. flavonoids fraction attenuates lipopolysaccharide-induced acute lung injury in mice.

    Science.gov (United States)

    Chu, Chunjun; Yao, Shi; Chen, Jinglei; Wei, Xiaochen; Xia, Long; Chen, Daofeng; Zhang, Jian

    2016-10-01

    Eupatorium lindleyanum DC., "Ye-Ma-Zhui" called by local residents in China, showed anti-inflammatory activity and is used to treat tracheitis. We had isolated and identified the flavonoids, diterpenoids and sesquiterpenes compounds from the herb. In the present study, we evaluated the protective effects of the flavonoids fraction of E. lindleyanum (EUP-FLA) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible underlying mechanisms of action. EUP-FLA could significantly decrease lung wet-to-dry weight (W/D) ratio, nitric oxide (NO) and protein concentration in BALF, lower myeloperoxidase (MPO) activity, increase superoxide dismutase (SOD) activity and down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Additionally, EUP-FLA attenuated lung histopathological changes and significantly reduced complement deposition with decreasing the levels of Complement 3 (C3) and Complement 3c (C3c) in serum. These results demonstrated that EUP-FLA may attenuate LPS-induced ALI via reducing productions of pro-inflammatory mediators, decreasing the level of complement and affecting the NO, SOD and MPO activity. PMID:27398612

  13. Ecto-5'-nucleotidase CD73 modulates the innate immune response to influenza infection but is not required for development of influenza-induced acute lung injury.

    Science.gov (United States)

    Aeffner, Famke; Woods, Parker S; Davis, Ian C

    2015-12-01

    Extracellular nucleotides and nucleosides are important signaling molecules in the lung. Nucleotide and nucleoside concentrations in alveolar lining fluid are controlled by a complex network of surface ectonucleotidases. Previously, we demonstrated that influenza A/WSN/33 (H1N1) virus resulted in increased levels of the nucleotide ATP and the nucleoside adenosine in bronchoalveolar lavage fluid (BALF) of wild-type (WT) C57BL/6 mice. Influenza-induced acute lung injury (ALI) was highly attenuated in A1-adenosine receptor-knockout mice. Because AMP hydrolysis by the ecto-5'-nucleotidase (CD73) plays a central role in and is rate-limiting for generation of adenosine in the normal lung, we hypothesized that ALI would be attenuated in C57BL/6-congenic CD73-knockout (CD73-KO) mice. Infection-induced hypoxemia, bradycardia, viral replication, and bronchoconstriction were moderately increased in CD73-KO mice relative to WT controls. However, postinfection weight loss, pulmonary edema, and parenchymal dysfunction were not altered. Treatment of WT mice with the CD73 inhibitor 5'-(α,β-methylene) diphosphate (APCP) also had no effect on infection-induced pulmonary edema but modestly attenuated hypoxemia. BALF from CD73-KO and APCP-treated WT mice contained more IL-6 and CXCL-10/IFN-γ-induced protein 10, less CXCL-1/keratinocyte chemoattractant, and fewer neutrophils than BALF from untreated WT controls. BALF from APCP-treated WT mice also contained fewer alveolar macrophages and more transforming growth factor-β than BALF from untreated WT mice. These results indicate that CD73 is not necessary for development of ALI following influenza A virus infection and suggest that tissue-nonspecific alkaline phosphatase may be responsible for increased adenosine generation in the infected lung. However, they do suggest that CD73 has a previously unrecognized immunomodulatory role in influenza. PMID:26432867

  14. Radioisotope albumin flux measurement of microvascular lung permeability: an independent parameter in acute respiratory failure?

    International Nuclear Information System (INIS)

    Aim: To evaluate the extent to which single measurements of microvascular lung permeability may be relevant as an additional parameter in a heterogenous clinical patient collective with Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). Methods: In 36 patients with pneumonia (13), non pneumogenic sepsis (9) or trauma (14) meeting the consensus conference criteria of ALI or ARDS double-isotope protein flux measurements (51Cr erythrocytes as intravascular tracer, Tc-99m human albumin as diffusible tracer) of microvascular lung permeability were performed using the Normalized Slope Index (NSI). The examination was to determine whether there is a relationship between the clinical diagnosis of ALI/ARDS, impaired permeability and clinical parameters, that is the underlying disease, oxygenation, duration of mechanical ventilation and mean pulmonary-artery pressure (PAP). Results: At the time of study, 25 patients presented with increased permeability (NSI > 1 x 10-3 min-1) indicating an exudative stage of disease, and 11 patients with normal permeability. The permeability impairment correlated with the underlying disease (p > 0.05). With respect to survival, there was a negative correlation to PAP (p < 0.01). Apart from that no correlations between the individual parameters were found. Especially no correlation was found between permeability impairment and oxygenation, duration of disease of PAP. Conclusion: In ALI and ARDS, pulmonary capillary permeability is a diagnostic parameter which is independent from clinical variables. Permeability measurement makes a stage classification (exudative versus non exudative phase) of ALI/ARDS possible based on a measurable pathophysiological correlate. (orig.)

  15. The role of tumor necrosis factor in increased airspace epithelial permeability in acute lung inflammation.

    Science.gov (United States)

    Li, X Y; Donaldson, K; Brown, D; MacNee, W

    1995-08-01

    Increased airspace epithelial permeability is an early event in lung inflammation and injury. In this study, we have developed a rat model to study the mechanisms of the epithelial permeability to 125iodine-labeled bovine serum albumin (125I-BSA), instilled intratracheally during acute lung inflammation. Epithelial permeability was measured as the percentage of instilled 125I-BSA appearing in the blood. The increase in epithelial permeability induced by intratracheal instillation of heat-killed Corynebacterium parvum produced a peak influx of neutrophils into the bronchoalveolar space at 16 h, which occurred after the peak increase in epithelial permeability (8 h). The increased epithelial permeability induced by C. parvum did not appear to be protease- or oxidant-mediated. Depletion of peripheral blood neutrophils was achieved by an intravenous injection of anti-neutrophil polyclonal antibody. The consequent profound reduction in neutrophil and macrophage influx into the airspaces 8 h after instillation of C. parvum reduced the epithelial permeability to control values. Bronchoalveolar lavage (BAL) leukocytes from rats 8 h, but not 16 h, after treatment with C. parvum caused a modest increase in epithelial permeability when re-instilled intratracheally into control rat lungs. Separation of the leukocytes before re-instillation indicated that macrophages rather than neutrophils were predominantly responsible for the increased epithelial permeability. The presence of dramatically increased levels of tumor necrosis factor (TNF) in BAL 8 h in contrast to a slight increase in BAL 16 h after C. parvum, the release of TNF from 8 h macrophages, the increased epithelial permeability induced by TNF in epithelial monolayers in vitro, and the inhibition of C. parvum-induced epithelial permeability by TNF antibody support the premise that TNF is a major player in the increased epithelial permeability that occurs during C. parvum-induced acute alveolitis. PMID:7626286

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

    OpenAIRE

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

    2016-01-01

    Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regula...

  17. The biological effects of higher and lower positive end-expiratory pressure in pulmonary and extrapulmonary acute lung injury with intra-abdominal hypertension

    OpenAIRE

    Santos, Cíntia Lourenco; Moraes, Lillian; Santos, Raquel Souza; dos Santos Samary, Cynthia; Silva, Johnatas Dutra; Morales, Marcelo Marcos; Capelozzi, Vera Lucia; de Abreu, Marcelo Gama; Schanaider, Alberto; Silva, Pedro Leme; Garcia, Cristiane Sousa Nascimento Baez; Pelosi, Paolo; Rocco, Patricia Rieken Macedo

    2014-01-01

    Introduction Mechanical ventilation with high positive end-expiratory pressure (PEEP) has been used in patients with acute respiratory distress syndrome (ARDS) and intra-abdominal hypertension (IAH), but the role of PEEP in minimizing lung injury remains controversial. We hypothesized that in the presence of acute lung injury (ALI) with IAH: 1) higher PEEP levels improve pulmonary morphofunction and minimize lung injury; and 2) the biological effects of higher PEEP are more effective in extra...

  18. Enhanced Resolution of Hyperoxic Acute Lung Injury as a result of Aspirin Triggered Resolvin D1 Treatment.

    Science.gov (United States)

    Cox, Ruan; Phillips, Oluwakemi; Fukumoto, Jutaro; Fukumoto, Itsuko; Parthasarathy, Prasanna Tamarapu; Arias, Stephen; Cho, Young; Lockey, Richard F; Kolliputi, Narasaiah

    2015-09-01

    Acute lung injury (ALI), which presents as acute respiratory failure, is a major clinical problem that requires aggressive care, and patients who require prolonged oxygen exposure are at risk of developing this disease. Although molecular determinants of ALI have been reported, the molecules involved in disease catabasis associated with oxygen toxicity have not been well studied. It has been reported that lung mucosa is rich in omega-3 fatty acid dicosahexanoic acid (DHA), which has antiinflammatory properties. Aspirin-triggered resolvin D1 (AT-RvD1) is a potent proresolution metabolite of DHA that can curb the inflammatory effects in various acute injuries, yet the effect of AT-RvD1 on hyperoxic acute lung injury (HALI) or in the oxygen toxicity setting in general has not been investigated. The effects of AT-RvD1 on HALI were determined for the first time in 8- to 10-week-old C57BL/6 mice that were exposed to hyperoxia (≥95% O2) for 48 hours. Mice were given AT-RvD1 (100 ng) in saline or a saline vehicle for 24 hours in normoxic (≈21% O2) conditions after hyperoxia. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected for analysis associated with proinflammatory signaling and lung inflammation. AT-RvD1 treatment resulted in reduced oxidative stress, increased glutathione production, and significantly decreased tissue inflammation. AT-RvD1 treatment also significantly reduced the lung wet/dry ratio, protein in BAL fluid, and decreased apoptotic and NF-κB signaling. These results show that AT-RvD1 curbs oxygen-induced lung edema, permeability, inflammation, and apoptosis and is thus an effective therapy for prolonged hyperoxia exposure in this murine model. PMID:25647402

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

    Directory of Open Access Journals (Sweden)

    Sarah M McMullen

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

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

    International Nuclear Information System (INIS)

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

  1. 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

  2. Children with chronic lung diseases have cognitive dysfunction as assessed by event-related potential (auditory P300) and Stanford-Binet IQ (SB-IV) test.

    Science.gov (United States)

    Kamel, Terez Boshra; Abd Elmonaem, Mahmoud Tarek; Khalil, Lobna Hamed; Goda, Mona Hamdy; Sanyelbhaa, Hossam; Ramzy, Mourad Alfy

    2016-10-01

    Chronic lung disease (CLD) in children represents a heterogeneous group of many clinico-pathological entities with risk of adverse impact of chronic or intermittent hypoxia. So far, few researchers have investigated the cognitive function in these children, and the role of auditory P300 in the assessment of their cognitive function has not been investigated yet. This study was designed to assess the cognitive functions among schoolchildren with different chronic pulmonary diseases using both auditory P300 and Stanford-Binet test. This cross-sectional study included 40 school-aged children who were suffering from chronic chest troubles other than asthma and 30 healthy children of similar age, gender and socioeconomic state as a control group. All subjects were evaluated through clinical examination, radiological evaluation and spirometry. Audiological evaluation included (basic otological examination, pure-tone, speech audiometry and immittancemetry). Cognitive function was assessed by auditory P300 and psychological evaluation using Stanford-Binet test (4th edition). Children with chronic lung diseases had significantly lower anthropometric measures compared to healthy controls. They had statistically significant lower IQ scores and delayed P300 latencies denoting lower cognitive abilities. Cognitive dysfunction correlated to severity of disease. P300 latencies were prolonged among hypoxic patients. Cognitive deficits in children with different chronic lung diseases were best detected using both Stanford-Binet test and auditory P300. P300 is an easy objective tool. P300 is affected early with hypoxia and could alarm subtle cognitive dysfunction. PMID:27075686

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

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

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

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

    OpenAIRE

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

    2008-01-01

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

  5. IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A(H1N1)Virus

    Institute of Scientific and Technical Information of China (English)

    Chenggang Li; Chen Wang; Zhongwei Chen; Li Xing; Chong Tang; Xiangwu Ju; Feng Guo; Jiejie Deng; Yan Zhao; Peng Yang; Jun Tang; Penghui Yang; Huanling Wang; Zhongpeng Zhao; Zhinan Yin; Bin Cao; Xiliang Wang; Chengyu Jiang; Yang Sun; Taisheng Li; Chen Wang; Zhong Wang; Zhen Zou; Yiwu Yan; Wei Wang

    2012-01-01

    The 2009 flu pandemic involved the emergence of a new strain of a swine-origin H1N1 influenza virus(S-OIV H1N1)that infected almost every country in the world.Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury.In this report,we are the first to describe a mouse model of S-OIV virus infection with acute lung injury and immune responses that reflect human clinical disease.The clinical efficacy of the antiviral oseltamivir(Tamiflu)administered in the early stages of S-OIV H1N1 infection was confirmed in the mouse model.Moreover,elevated levels of IL-17,Th-17 mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing.IL-17 deficiency or treatment with monoclonal antibodies against IL-17-ameliorated acute lung injury induced by the S-OIV H1N1 virus in mice.These results suggest that IL-17 plays an important role in S-OIV-induced acute lung injury and that monoclonal antibodies against IL-17 could be useful as a potential therapeutic remedy for future S-OIV H1N1 pandemics.

  6. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    Science.gov (United States)

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

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

    Science.gov (United States)

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

    2015-10-01

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

  8. Adenoviral augmentation of elafin protects the lung against acute injury mediated by activated neutrophils and bacterial infection.

    Science.gov (United States)

    Simpson, A J; Wallace, W A; Marsden, M E; Govan, J R; Porteous, D J; Haslett, C; Sallenave, J M

    2001-08-01

    During acute pulmonary infection, tissue injury may be secondary to the effects of bacterial products or to the effects of the host inflammatory response. An attractive strategy for tissue protection in this setting would combine antimicrobial activity with inhibition of human neutrophil elastase (HNE), a key effector of neutrophil-mediated tissue injury. We postulated that genetic augmentation of elafin (an endogenous inhibitor of HNE with intrinsic antimicrobial activity) could protect the lung against acute inflammatory injury without detriment to host defense. A replication-deficient adenovirus encoding elafin cDNA significantly protected A549 cells against the injurious effects of both HNE and whole activated human neutrophils in vitro. Intratracheal replication-deficient adenovirus encoding elafin cDNA significantly protected murine lungs against injury mediated by Pseudomonas aeruginosa in vivo. Genetic augmentation of elafin therefore has the capacity to protect the lung against the injurious effects of both bacterial pathogens resistant to conventional antibiotics and activated neutrophils. PMID:11466403

  9. Effects and mechanism analysis of combined infusion by levosimendan and vasopressin on acute lung injury in rats septic shock.

    Science.gov (United States)

    Wang, Xuebing; Ma, Shaolin; Liu, Yang; Xu, Wei; Li, Zhanxia

    2014-12-01

    This research is aimed to discover the influence and underling mechanism of combined infusion of arginine vasopressin with levosimendan on acute lung injury in rat septic shock with norepinephrine supplemented. The traditional fecal peritonitis-induced septic shock model was undergone in rats for study. It is observed that the combined infusion supplemented with norepinephrine brought about a lower mean pulmonary artery pressure; lower high-mobility group box 1 levels, pulmonary levels of interleukin-6, and arterial total nitrate/nitrite; lower apoptotic cells scores and total histological scores; but higher pulmonary gas exchange when compared with the separate infusion group and norepinephrine group. This therapy shows potential clinical beneficial assistance in sepsis-induced acute lung injury. The results suggest the mechanism of such effect is through abating pulmonary artery pressure, and more importantly suppressing inflammatory responses in lung when compared with norepinephrine infusion group and the separate infusion of levosimendan or vasopressin alone. PMID:25002345

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    the use of sonographic examination of the heart, lungs and deep veins, performed within one hour of the primary evaluation, in acute admitted patients with respiratory symptoms. Methods: We performed a prospective cross sectional blinded observational study, conducted in a medical emergency department....... Patients were included if one or more of the following symptoms or clinical findings were present: respiratory rate > 20, saturation lungs and deep veins...... with pulmonary oedema, 1 had pericardial effusion, 1 had massive pleural effusion, 5 had empyema and 4 had pulmonary embolism. Conclusion: Focused sonography of the heart, lungs and deep veins is a highly feasible and non-invasive bedside method. In acute admitted patients with respiratory symptoms, it may help...

  11. Amisulpride-induced acute akathisia in OCD: an example of dysfunctional dopamine-serotonin interactions?

    Science.gov (United States)

    Ersche, Karen D; Cumming, Paul; Craig, Kevin J; Müller, Ulrich; Fineberg, Naomi A; Bullmore, Edward T; Robbins, Trevor W

    2012-06-01

    We report about a clinical observation in a well-characterized group of patients with obsessive-compulsive disorder (OCD) during an experimental medicine study in which a single dose of amisulpride (a selective D₂/₃ antagonist) was administered. Almost half of the OCD patients, in particular those with less severe obsessive-compulsive symptoms, experienced acute akathisia in response to the amisulpride challenge. This unexpectedly high incidence of akathisia in the selective serotonin reuptake inhibitor (SSRI)-treated patients with OCD suggests that individual differences in dopamine-serotonin interactions underlie the clinical heterogeneity of OCD, and may thus explain the insufficiency of SSRI monotherapy in those patients not experiencing a satisfactory outcome in symptom reduction. We further speculate about the neuropathology possibly underlying this clinical observation and outline a testable hypothesis for future molecular imaging studies.

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

    International Nuclear Information System (INIS)

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

  13. 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.

  14. Interaction of dependent and non-dependent regions of the acutely injured lung during a stepwise recruitment manoeuvre

    International Nuclear Information System (INIS)

    The benefit of treating acute lung injury with recruitment manoeuvres is controversial. An impediment to settling this debate is the difficulty in visualizing how distinct lung regions respond to the manoeuvre. Here, regional lung mechanics were studied by electrical impedance tomography (EIT) during a stepwise recruitment manoeuvre in a porcine model with acute lung injury. The following interaction between dependent and non-dependent regions consistently occurred: atelectasis in the most dependent region was reversed only after the non-dependent region became overdistended. EIT estimates of overdistension and atelectasis were validated by histological examination of lung tissue, confirming that the dependent region was primarily atelectatic and the non-dependent region was primarily overdistended. The pulmonary pressure–volume equation, originally designed for modelling measurements at the airway opening, was adapted for EIT-based regional estimates of overdistension and atelectasis. The adaptation accurately modelled the regional EIT data from dependent and non-dependent regions (R2 > 0.93, P < 0.0001) and predicted their interaction during recruitment. In conclusion, EIT imaging of regional lung mechanics reveals that overdistension in the non-dependent region precedes atelectasis reversal in the dependent region during a stepwise recruitment manoeuvre. (paper)

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

    OpenAIRE

    Rossi, Patrik

    2006-01-01

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

  16. Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Olivia Meira Dias

    2014-01-01

    Full Text Available The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs. There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    data demonstrated a statistically insignificant effect of iNO on duration of ventilation, ventilator-free days, and length of stay in the intensive care unit and hospital. We found a statistically significant but transient improvement in oxygenation in the first 24 hours, expressed as the ratio of Po2......BACKGROUND: Acute hypoxemic respiratory failure, defined as acute lung injury and acute respiratory distress syndrome, are critical conditions associated with frequent mortality and morbidity in all ages. Inhaled nitric oxide (iNO) has been used to improve oxygenation, but its role remains...... be recommended for patients with acute hypoxemic respiratory failure. iNO results in a transient improvement in oxygenation but does not reduce mortality and may be harmful....

  18. Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model.

    Science.gov (United States)

    Noth, Rainer; Häsler, Robert; Stüber, Eckhard; Ellrichmann, Mark; Schäfer, Heiner; Geismann, Claudia; Hampe, Jochen; Bewig, Burkhard; Wedel, Thilo; Böttner, Martina; Schreiber, Stefan; Rosenstiel, Philip; Arlt, Alexander

    2013-04-01

    Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.

  19. Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

    Directory of Open Access Journals (Sweden)

    Dongdong Liu

    2014-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

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

    Science.gov (United States)

    Gao, Zhenming; Xu, Junfeng; Sun, Deguang; Zhang, Rixin; Liang, Rui; Wang, Liming; Fan, Rong

    2014-12-01

    Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-α (TNF-α), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-α and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (PSAP via the upregulation of AQP-1, which suppresses TNF-α expression. PMID:25371738

  1. β1-Na(+),K(+)-ATPase gene therapy upregulates tight junctions to rescue lipopolysaccharide-induced acute lung injury.

    Science.gov (United States)

    Lin, X; Barravecchia, M; Kothari, P; Young, J L; Dean, D A

    2016-06-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with diverse disorders and characterized by disruption of the alveolar-capillary barrier, leakage of edema fluid into the lung, and substantial inflammation leading to acute respiratory failure. Gene therapy is a potentially powerful approach to treat ALI/ARDS through repair of alveolar epithelial function. Herein, we show that delivery of a plasmid expressing β1-subunit of the Na(+),K(+)-ATPase (β1-Na(+),K(+)-ATPase) alone or in combination with epithelial sodium channel (ENaC) α1-subunit using electroporation not only protected from subsequent lipopolysaccharide (LPS)-mediated lung injury, but also treated injured lungs. However, transfer of α1-subunit of ENaC (α1-ENaC) alone only provided protection benefit rather than treatment benefit although alveolar fluid clearance had been remarkably enhanced. Gene transfer of β1-Na(+),K(+)-ATPase, but not α1-ENaC, not only enhanced expression of tight junction protein zona occludins-1 (ZO-1) and occludin both in cultured cells and in mouse lungs, but also reduced pre-existing increase of lung permeability in vivo. These results demonstrate that gene transfer of β1-Na(+),K(+)-ATPase upregulates tight junction formation and therefore treats lungs with existing injury, whereas delivery of α1-ENaC only maintains pre-existing tight junction but not for generation. This indicates that the restoration of epithelial/endothelial barrier function may provide better treatment of ALI/ARDS. PMID:26910760

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

    Institute of Scientific and Technical Information of China (English)

    陶军; 杨天德; 陈祥瑞; 黄河

    2004-01-01

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

  3. Rabdosia japonica var. glaucocalyx Flavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Chun-jun Chu

    2014-01-01

    Full Text Available Rabdosia japonica var. glaucocalyx (Maxim. Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim. Hara (RJFs in acute lung injury (ALI mice induced by lipopolysaccharide (LPS. Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3 in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF-α, IL-6, and IL-1β, and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO activity and nitric oxide (NO and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.

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

    International Nuclear Information System (INIS)

    A 73-year-old man presented with dyspnea, cough, fever, appetite loss and stridor due to bronchial stenosis. Fiber-optic bronchoscopy revealed an endobronchial lesion in the right main bronchus and biopsy specimens showed poorly differentiated squamous cell carcinoma. The clinical stage of lung cancer was IIIB (T4N2M0). The patient received 60 Gy in 30 fractions over 43 days to a field including the right hilum and mediastinum. The tumor decreased in size and stenosis of the bronchus disappeared. A week after completion of radiation the patient began to have high grade fever and dyspnea, and progressive hypoxia developed. A chest radiograph showed diffuse bilateral interstitial infiltrates. Despite mechanical ventilation with PEEP and the administration of steroids, he died of respiratory failure three weeks after completion of radiation. Necropsy specimens obtained from the left lung revealed massive deposition of fibrin in the alveolar airspaces associated with hyaline membranes and hyperplasia of type II cells indicating diffuse alveolar damage. The patient had mild pulmonary fibrosis on a CT scan taken before the start of radiotherapy. We conclude that care should be taken if the case has pulmonary fibrosis because radiation therapy can precipitate severe radiation pneumonitis and acute respiratory distress syndrome in such cases. (author)

  5. Increased extravascular lung water reduces the efficacy of alveolar recruitment maneuver in acute respiratory distress syndrome.

    Science.gov (United States)

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

    2012-01-01

    Introduction. In acute respiratory distress syndrome (ARDS) the recruitment maneuver (RM) is used to reexpand atelectatic areas of the lungs aiming to improve arterial oxygenation. The goal of our paper was to evaluate the response to RM, as assessed by measurements of extravascular lung water index (EVLWI) in ARDS patients. Materials and Methods. Seventeen adult ARDS patients were enrolled into a prospective study. Patients received protective ventilation. The RM was performed by applying a continuous positive airway pressure of 40 cm H(2)O for 40 sec. The efficacy of the RM was assessed 5 min later. Patients were identified as responders if PaO(2)/FiO(2) increased by >20% above the baseline. EVLWI was assessed by transpulmonary thermodilution before the RM, and patients were divided into groups of low EVLWI (recruitment maneuver might be related to the severity of pulmonary edema. In patients with incresed EVLWI, the recruitment maneuver is less effective. PMID:22649717

  6. Acute lung injury induced by H9N2 virus in mice

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Shan Yunfeng; Chi Ying; Wen Tian; Han Xiaodong

    2014-01-01

    Background H9N2 avian influenza viruses (AIVs) have repeatedly caused infections in mammals even humans in many countries.The purpose of our study was to evaluate the acute lung injury (ALI) caused by H9N2 viral infection in mice.Methods Six-to eight-week-old female SPF C57BL/6 mice were infected intranasally with 1x104 MID50 of A/HONG KONG/2108/2003 [H9N2 (HK)] virus.Clinical signs,pathological changes,virus titration in tissues of mice,arterial blood gas,and cytokines in bronchoalveolar lavage fluid (BALF) and serum were observed at different time points after AIV infection.Results H9N2-AIV-infected mice exhibited severe respiratory syndrome,with a mortality rate of 50%.Lung histopathological changes in infected mice included diffuse pneumonia,alveolar damage,inflammatory cellular infiltration,interstitial and alveolar edema,and hemorrhage.In addition,H9N2 viral infection resulted in severe progressive hypoxemia,lymphopenia,and a significant increase in interleukin 1,interleukin 6,tumor necrosis factor,and interferon in BALF and serum.Conclusions The results suggest that H9N2 viral infection induces a typical ALl in mice that resembles the common features of ALl.Our data may facilitate the future studies of potential avian H9N2 disease in humans.

  7. Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans.

    Science.gov (United States)

    Pleiner, Johannes; Heere-Ress, Elisabeth; Langenberger, Herbert; Sieder, Anna E; Bayerle-Eder, Michaela; Mittermayer, Fritz; Fuchsjäger-Mayrl, Gabriele; Böhm, Johannes; Jansen, Burkhard; Wolzt, Michael

    2002-01-01

    Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N(G)-monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (P<0.0005) and heart rate (P<0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by approximately 50% (P<0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS.

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

    Directory of Open Access Journals (Sweden)

    Daisuke Osaka, Yoko Shibata, Kazunori Kanouchi, Michiko Nishiwaki, Tomomi Kimura, Hiroyuki Kishi, Shuichi Abe, Sumito Inoue, Yoshikane Tokairin, Akira Igarashi, Keiko Yamauchi, Yasuko Aida, Takako Nemoto, Keiko Nunomiya, Koji Fukuzaki, Isao Kubota

    2011-01-01

    Full Text Available Background: Pneumonia is still one of the most frequent causes of death in the elderly. Complication of acute lung injury (ALI/acute respiratory distress syndrome (ARDS by pneumonia makes patients very ill due to severe respiratory failure. Biomarkers that can discriminate the presence of complicating ALI/ARDS are required for early detection. The aim of this research was to investigate whether soluble endothelial selectin (sES could be a biomarker for ALI.Methods: Serum sES levels were measured in 27 pneumonia patients, who were enrolled between April 2006 and September 2007. Among these patients, six had ALI or a condition that was clinically comparable to ALI (cALI. All patients who were enrolled were successfully treated and survived.Results: Circulating sES levels were elevated in pneumonia patients with ALI/cALI, and sES levels decreased following treatment of their pneumonia. Univariate and multivariate logistic regression analyses showed that sES was the only significant factor for identifying complicating ALI/cALI, independently of C-reactive protein (CRP and lactate dehydrogenase (LDH. By receiver operating characteristic (ROC curve analysis, the cut-off value for sES was 40.1 ng/mL, with a sensitivity of 0.8 and a specificity of 0.8.Conclusion: sES may be a useful biomarker for discriminating complicating ALI/cALI in patients with severe pneumonia.

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

    International Nuclear Information System (INIS)

    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 (FiO2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 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

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

    OpenAIRE

    Suarez Sipmann, Fernando

    2008-01-01

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

  11. Early-age-related changes in proteostasis augment immunopathogenesis of sepsis and acute lung injury.

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    Manish Bodas

    Full Text Available BACKGROUND: The decline of proteasomal activity is known to be associated with the age-related disorders but the early events involved in this process are not apparent. To address this, we investigated the early-age-related (pediatric vs. adult mechanisms that augment immunopathogenesis of sepsis and acute lung injury. METHODOLOGY/PRINCIPAL FINDINGS: The 3-weeks (pediatric and 6-months (adult old C57BL/6 mice were selected as the study groups. Mice were subjected to 1×20 cecal ligation and puncture (CLP mediated sepsis or intratracheal Psuedomonas aeruginosa (Pa-LPS induced acute lung injury (ALI.We observed a significant increase in basal levels of pro-inflammatory cytokine, IL-6 and neutrophil activity marker, myeloperoxidase (MPO in the adult mice compared to the pediatric indicating the age-related constitutive increase in inflammatory response. Next, we found that age-related decrease in PSMB6 (proteasomal subunit expression in adult mice results in accumulation of ubiquitinated proteins that triggers the unfolded protein response (UPR. We identified that Pa-LPS induced activation of UPR modifier, p97/VCP (valosin-containing protein in the adult mice lungs correlates with increase in Pa-LPS induced NFκB levels. Moreover, we observed a constitutive increase in p-eIF2α indicating a protective ER stress response to accumulation of ubiquitinated-proteins. We used MG-132 treatment of HBE cells as an in vitro model to standardize the efficacy of salubrinal (inhibitor of eIF2α de-phosphorylation in controlling the accumulation of ubiquitinated proteins and the NFκB levels. Finally, we evaluated the therapeutic efficacy of salubrinal to correct proteostasis-imbalance in the adult mice based on its ability to control CLP induced IL-6 secretion or recruitment of pro-inflammatory cells. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the critical role of early-age-related proteostasis-imbalance as a novel mechanism that augments the NFκB mediated

  12. 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.

  13. 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

  14. Right ventricular dysfunction as predictor of longer hospital stay in patients with acute decompensated heart failure: a prospective study in Indonesian population

    OpenAIRE

    Yamin, Paskariatne Probo Dewi; Raharjo, Sunu Budhi; Putri, Vebiona Kartini Prima; Hersunarti, Nani

    2016-01-01

    Background Hospital length of stay (LOS) is a key determinant of heart failure hospitalization costs. Longer LOS is associated with lower quality of care measures and higher rates of readmission and mortality. Right ventricular (RV) dysfunction predicted poor outcomes in patients with stable chronic heart failure (CHF), however, its prognostic value in the acute decompensated heart failure (ADHF) patients has not been sufficiently clarified. This study investigated the prognostic value of RV ...

  15. After the chemotherapy: potential mechanisms for chemotherapy-induced delayed skeletal muscle dysfunction in survivors of acute lymphoblastic leukaemia in childhood

    OpenAIRE

    Celena eScheede-Bergdahl; R Thomas Jagoe

    2013-01-01

    There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukaemia (ALL), have increased rates of longterm skeletal muscle dysfunction. This places them at higher risk of physical restriction and functional impairment as well as potentially contributing to observed increases in cardiovascular disease and insulin resistance in later life. The mechanisms underlying these changes in skeletal muscle are unknown but chemotherapy drugs used in treatment for ALL are strong...

  16. Immune dysfunction in cirrhosis

    OpenAIRE

    Sipeki Nóra; Antal-Szalmás Péter (1968-) (laboratóriumi szakorvos, laboratóriumi hematológus és immunológus, klinikai farmakológus szakorvos); Lakatos Péter László; Papp Mária (1975-) (belgyógyász, gasztroenterológus)

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific comp...

  17. Effect of resveratrol on microcirculation disorder and lung injury following severe acute pancreatitis in rats

    Institute of Scientific and Technical Information of China (English)

    Yong Meng; Mei Zhang; Jun Xu; Xue-Min Liu; Qing-Yong Ma

    2005-01-01

    AIM: To investigate the mechanism of resveratrol underlying the microcirculation disorder and lung injury following severe acute pancreatitis (SAP).METHODS: Twenty-four rats were divided into 3 groups (SAP, sham and resveratrol groups) randomly. SAP model was established by injecting 4% sodium taurocholate 1 mL/kg through puncturing pancreatic ducts. Sham (control) group (8 rats) was established by turning over the duodenum.Resveratrol was given at 0.1 mg/kg b.m. intraperitoneally.Rats were sacrificed 9 h after SAP was induced. Blood samples were obtained for hemorrheological examination.Lung tissues were used for pathological observation, and examination of microvascular permeability, dry/wet ratio and myeloperoxidase (MPO) activity. Gene expression of intercellular adhesion molecule-1 (ICAM-1) was detected by RT-PCR.RESULTS: Compared with SAP group, resveratrol relieved the edema and infiltration of leukocytes in the lungs. Resveratrol improved markers of hemorrheology:high VTB (5.77±1.18 mPas vs9.49±1.34 mPas), low VTB (16.12±3.20 mPas vs30.91±7.28 mPas), PV (4.69±1.68 mPas vs8.00±1.34 mPas), BSR (1.25±0.42 mm/h vs 0.03±0.03mm/h), VPC (54.67±3.08% vs 62.17±3.39%), fibrinogen (203.2±87.8 g/L vs 51.3±19.1 g/L), original hemolysis (0.45±0.02 vs 0.49±0.02), and complete hemolysis (0.41±0.02 vs0.43±0.02) (P<0.05). Resveratrol decreased the OD ratio of ICAM-1 gene (0.800±0.03 vs 1.188±0.10),dry/wet ratio (0.74±0.02 vs 0.77±0.03), microvascular permeability (0.079±0.006 vs 0.112±0.004) and MPO activity (4.42±0.32 vs 5.03±0.51) significantly (P<0.05).CONCLUSION: Resveratrol can improve the microcirculation disorder of the lung by decreasing leukocyte-endothelial interaction, reducing blood viscosity, improving the decrease of blood flow, and stabilizing erythrocytes in SAP rats. It may be a potential candidate to treat SAP and its severe complications (ALI).

  18. 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.

  19. 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.

  20. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

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    Sandrine Peruchon

    Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

  1. The role of JAK2/STAT3 signaling pathway in the lung injury rat with severe acute pancreatitis

    OpenAIRE

    Min-li LI; Zhu, Ren-Min; Zhang, Xiao-Hua; Jing-yun GUO; Yang, Miao-Fang; Xiao-wei WU; Mei-xia GUO

    2011-01-01

    Objective To investigate the mechanism of action of JAK/STAT signaling pathways in the lung injury of experimental severe acute pancreatitis(SAP).Methods The rat model of SAP was reproduced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct.Thirty-two male SD rats were randomly assigned into 4 groups(8 each): normal control group(NC),SAP 6h,12h and 18h groups.The level of serum amylase(AMY) was measured dynamically.The pathological changes in pancreas and lung wer...

  2. Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis

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    Matsuda Akihisa

    2012-08-01

    Full Text Available Abstract Background A previous meta-analysis reported a positive association between an insertion/deletion (I/D polymorphism in the angiotensin-converting enzyme gene (ACE and the risk of acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. Methods We searched electronic databases through October 2011 for the terms “angiotensin-converting enzyme gene”, “acute lung injury”, and “acute respiratory distress syndrome,” and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. Results The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects ( Pallele Pdominant = 0.001, Precessive = 0.002. This finding remained significant after correction for multiple comparisons. Conclusions There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.

  3. Effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome

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    Mao ZR

    2016-02-01

    Full Text Available Zhengrong Mao,1 Haifeng Wang2,3 1Department of Critical Care Medicine, The First Affiliated Hospital of Henan, University of Traditional Chinese Medicine, 2Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, 3Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Zhengzhou City, Henan, People’s Republic of China Objective: To observe the effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome. Subjects and methods: A total of 53 patients with exogenous pulmonary acute respiratory distress syndrome, who were admitted to the intensive care unit of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from March 2009 to February 2013, were selected. They were randomly divided into the treatment group (25 cases and the control group (28 cases. Both the groups were treated with conventional treatment and lung-protective ventilation strategy; apart from these, enema therapy with Xuanbai Chengqi decoction was given to the treatment group. Meanwhile, static lung compliance, dynamic lung compliance, peak airway pressure, plateau pressure, and positive end-expiratory pressure (PEEP for patients in both the groups were observed and recorded at 24, 48, and 72 hours after the drug was used. Moreover, variations in the duration of parenteral nutrition, incidence rate of complications, and case fatality rate in patients after treatment were recorded. Results: For patients in the treatment group, at 48 and 72 hours after treatment, the static lung compliance and dynamic lung compliance were significantly higher than those in the control group, while plateau pressure, peak airway pressure, and PEEP were significantly lower than those before treatment. At the same time, PEEP for patients in the treatment group at 72

  4. Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Nørgaard, Astrid; Iversen, Martin;

    2010-01-01

    Regulatory T cells (Tregs) have been related to acute rejection as have the cytotoxic T cells, their immunological counterpart. High expression of cytotoxic markers has been related to acute rejection incidents following both kidney and intestine transplantation, while the correlation between FoxP3...... expression and acute rejection is still being debated. Some studies have been performed on blood samples from lung-transplanted patients, while others have investigated the local immune response in the lungs by analysing broncho-alveolar-lavage (BAL) fluids or biopsies. Biopsies are considered the gold...... standard in diagnosis of acute rejection....

  5. Pulmonary clearance of 99mTc-DTPA and 99mTc-albumin in rabbits with surfactant dysfunction and lung injury

    International Nuclear Information System (INIS)

    We measured the pulmonary clearance of inhaled 99mTc-DTPA and 99mTc-albumin in rabbits with surfacant dysfunction induced by dioctyl sodium sulphosuccinate and in rabbits with lung injury induced by oleic acid. After inhalation of 99mTc-albumin in ten animals, clearance of the tracer from the lungs was monitored for 90 min. The first 30 min was a control period. Dioctyl sodium sulphosuccinate was then administered in aerosol and after another 30 min oleic acid was injected intravenously. Ten other rabbits were given 99mTc-DTPA, and clearance was externally recorded for 60 min. Five animals inhaled detergent aerosol and five animals were given oleic acid intravenously after 30 min. Airway pressures, tidal volume, and arterial blood gases were measured before and after each intervention. The half-life of 99mTc-albumin in the lung was 442 ± 123 min during the control period, 363 ± 52 min after detergent administration, and 134 ± 18 min after oleic acid administration. The half-life of 99mTc-DTPA was 94 ± 16 min before and 10 ± 0.6 min after detergent administration and 75 ± 12 min before and 18 ± 1.8 min after oleic acid administration. Gas exchange was not affected by administration of dioctyl sodium sulphosuccinate but markedly impaired after injection of oleic acid. Compliance of the respiratory system remained unaffected by detergent but decreased after injection of oleic acid. The results indicate that the rate limiting factors for the alveolo-capillary transfer of 99mTc-albumin and 99mTc-DTPA are different. Surfactant dysfunction affects the transfer of 99mTc-DTPA but not 99mTc-albumin. (author)

  6. Acute Lung Injury Is Reduced in fat-1 Mice Endogenously Synthesizing n-3 Fatty Acids

    Science.gov (United States)

    Mayer, Konstantin; Kiessling, Almuth; Ott, Juliane; Schaefer, Martina Barbara; Hecker, Matthias; Henneke, Ingrid; Schulz, Richard; Günther, Andreas; Wang, Jingdong; Wu, Lijun; Roth, Joachim; Seeger, Werner; Kang, Jing X.

    2009-01-01

    Rationale: Acute lung injury (ALI) remains an important cause of mortality in intensive care units. Inflammation is controlled by cytokines and eicosanoids derived from the n-6 fatty acid (FA) arachidonic acid (AA). The n-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and mediators derived from EPA and DHA possess reduced inflammatory potency. Objectives: To determine whether the ability of fat-1 mice to endogenously convert n-6 to n-3 FA, and thus generate an increased ratio of n-3 to n-6 FA, impacts experimental ALI. Methods: We investigated ALI induced by intratracheal instillation of endotoxin in fat-1 and wild-type (WT) mice, assessing leukocyte numbers, protein concentration, and prostaglandin and cytokine levels in bronchoalveolar lavage fluid, as well as free FA in plasma, and lung ventilator compliance. Body temperature and motor activity of mice—markers of sickness behavior—were also recorded. Measurements and Main Results: In ALI, fat-1 mice exhibited significantly reduced leukocyte invasion, protein leakage, and macrophage inflammatory protein-2 and thromboxane B2 levels in lavage fluid compared with WT mice. Free AA levels were increased in the plasma of WT mice in response to endotoxin, whereas EPA and DHA were increased in the fat-1 group. Ventilator compliance was significantly improved in fat-1 mice. Body temperature and motor activity were decreased in ALI. fat-1 Mice recovered body temperature and motor activity faster. Conclusions: fat-1 Mice exhibited reduced features of ALI and sickness behavior. Increasing the availability of n-3 FA may thus be beneficial in critically ill patients with ALI. PMID:19136374

  7. DISFUNCIÓN DIASTÓLICA EN EL INFARTO AGUDO DE MIOCARDIO / Diastolic dysfunction in acute myocardial infarction

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    Norge Ramón Lara Pérez

    2010-03-01

    Full Text Available Introduction and objectives: Ischemic heart disease is among the first causes of disability and death in the world. The acute myocardial infarction alters considerably the myocardial relaxation. The echocardiogram is a useful, economic and harmless method to assess diastolic function in these patients; that is why the aim of the study was to characterize the behavior of this left ventricular function by means of an echocardiography. Methods: an observational descriptive study was carried out with 91 patients with myocardial infarction who were hospitalized at the Cardiology Ward of the Arnaldo Milian Castro Provincial University Hospital in Santa Clara during 2008. An echocardiogram was performed between the fifth and the seventh day of evolution, and the patterns of diastolic function were compared with other variables. Results: There was a prevalence of the male sex (74,7 %, the infarctions without ST segment elevation were more frequent (83,1 % – which showed a bigger alteration of the relaxation, much more when the anterior and lateral walls of the left ventricle were involved. The presence of complications was linked to a bigger alteration of the relaxation, and the most associate ones were the contractile dysfunction and malignant arrhythmias. The decrease of the ejection fraction was linked to (p = 0,000 the prolongation of the relaxation. Conclusions: There was a prevalence of the infarction without ST segment elevation. It was more frequent in the male sex and it was associated with a higher level of alteration of the relaxation. The infarctions with anterior or lateral location, and those which caused complications, presented a higher level of this alteration. All patients with a reduced ejection fraction had relaxation disorders.

  8. Related research between right ventricular dysfunction and pulmonary embolism range of the patients with acute pulmonary thromboembolism

    International Nuclear Information System (INIS)

    Objective: The presence of right ventrieular dysfunction (RVD) increases morbidity and mortality of the patient with pulmonary thromboembolism (PTE). The aims of this study were to evaluate the relation between RVD on echocardiography and pulmonary embolism range on radionuclide palmonary ventilation-perfusion (V/Q) scan of the patients with acute PTE, and to discuss the diagnostic feasibility of RVD by pulmonary embolism range. Methods: All 348 patients with proven PTE were classified as two groups according to the echocardiography diagnosis. Two hundreds and twelve were with RVD and 136 were with normal right ventricular function (N-RVF). All underwent pulmonary V/Q imping.Statistical analysis was performed with SPSS 11.5, and the relation between RVD and pulmonary embolism range was performed with χ2 analysis, correlation analysis, receiver operating characteristic (ROC) curve analysis. Results: Signiticant relations between RVD (right/left ventricular end-diastolic diameter ratio (RVD/LVD)=0.52 ± 0.22. right/left ventricular transverse diameter ratio (RVTD/LVTD) =0.88 ± 0.26, tricuspid regurgitant pressure gradient (TRPG) = (31.93 ± 21.79) nun Hg (1 mm Hg = 0.133 kPa) and right ventricular anterior wall moilon (RVAWM) = (5.77 ± 1.99) mm) and pulmonary embolism range (1 ∼ 36, 11.4 ± 7.1) RVF and RVD and larger embolism range in RVD than in N-RVF (χ2=445.93, P2.58, P<0.01. Conclusion: The pulmonary embolism area waft negatively correlated with the RVD and had potential of being one of the references for the impression of RVD in PTE patients. (authors)

  9. Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury.

    Science.gov (United States)

    Santana, Maria Cristina E; Garcia, Cristiane S N B; Xisto, Débora G; Nagato, Lilian K S; Lassance, Roberta M; Prota, Luiz Felipe M; Ornellas, Felipe M; Capelozzi, Vera L; Morales, Marcelo M; Zin, Walter A; Pelosi, Paolo; Rocco, Patricia R M

    2009-06-30

    Prone position may delay the development of ventilator-induced lung injury (VILI), but the mechanisms require better elucidation. In experimental mild acute lung injury (ALI), arterial oxygen partial pressure (Pa O2), lung mechanics and histology, inflammatory markers [interleukin (IL)-6 and IL-1 beta], and type III procollagen (PCIII) mRNA expressions were analysed in supine and prone position. Wistar rats were randomly divided into two groups. In controls, saline was intraperitoneally injected while ALI was induced by paraquat. After 24-h, the animals were mechanically ventilated for 1-h in supine or prone positions. In ALI, prone position led to a better blood flow/tissue ratio both in ventral and dorsal regions and was associated with a more homogeneous distribution of alveolar aeration/tissue ratio reducing lung static elastance and viscoelastic pressure, and increasing end-expiratory lung volume and Pa O2. PCIII expression was higher in the ventral than dorsal region in supine position, with no regional changes in inflammatory markers. In conclusion, prone position may protect the lungs against VILI, thus reducing pulmonary stress and strain.

  10. 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.

  11. Clinical characteristics and outcomes of patients with acute lung injury and ARDS

    Directory of Open Access Journals (Sweden)

    R R Bhadade

    2011-01-01

    Full Text Available Background : Acute lung injury (ALI and acute respiratory distress syndrome (ARDS are critical illnesses associated with significant morbidity and mortality. Aims : This was designed to assess various etiologies of ALI/ARDS, to determine the correlation between the diagnostic criteria and need of mechanical ventilation, and to correlate biochemical factors with the outcome of patients. Settings and Design : An observational, prospective study was conducted in a medical intensive care unit (MICU of a tertiary care hospital, for a period of 1 year. Materials and Methods : This study encompassed 58 consecutive cases of ALI/ARDS admitted to a MICU as per AECC guidelines. Patients excluded were with cardiac failure, chronic kidney diseases with fluid overload, and age below 12 years. Statistical Analysis : The data were analysed applying χ2 -test, multivariate logistic regression analysis of significance, using computer-based program SPSS. Results : There were more males (74% than females, and presentation was more common in the younger age group, with a total mortality of 57%. Factors attributable for ALI/ARDS were malaria in 16 patients (27.6%, leptospirosis in 12 (20.7%, malaria with dengue in 3 (5.2%, undiagnosed fever in 16 (27.6%, pneumonia in 8 (13.8%, urinary tract infection in 2 (3.4%, and pancreatitis in 1 (1.7% patient. Out of 41 patients with PaO 2 /FiO 2 200, 11 patients though initially managed on noninvasive ventilation (NIV subsequently required invasive ventilation, and remaining six were successfully managed on NIV. Out of 41 patients requiring mechanical ventilation, 36 had LIS >2.5, whereas only 3 out of 17 patients with LIS <2.5 required mechanical ventilation. Conclusion : Malaria, leptospirosis, and undiagnosed fever were the main etiologies followed by pneumonia, urinary tract infections, and pancreatitis. Both the PaO 2 /FiO 2 ratio and lung injury score (LIS at the time of admission were significant predictors of the

  12. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Yi, Jae-Youn [Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Hyun-Gyu [Department of Microbiology and Immunology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  13. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

    International Nuclear Information System (INIS)

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer

  14. α1-ANTITRYPSIN ATTENUATES ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN RABBITS

    Institute of Scientific and Technical Information of China (English)

    揭志军; 蔡映云; 杨文兰; 金美玲; 朱威; 祝慈芳

    2003-01-01

    Objective To investigate whether pretreatment with α1-AT can attenuate acute lung injury (ALI) in rabbits induced with endotoxin. Methods Thirty-two New Zealand rabbits were randomly assigned to four groups(n=8):1.Infusion of endotoxin(Lipopolysaccharide,LPS 500μg/kg)without α1-AT (group LPS).2.Infusion α1-AT 120mg/kg at 15min before challenge with LPS(group LAV).3.Infusion of α1-AT 120mg/kg(group AAT).4 Infusion of saline 4ml/kg as control (group NS).Arterial blood gases,peripheral leukocyte counts and airway pressure were recorded every 1h.Physiologic intrapulmonary shunting (Qs/Qt) was measured every 4h.After 8h the bloods were collected for measurement of plasma concentration and activity of α1-AT.Then bronchoalveolar lavage fluid (BALF)was collected for measurement of concentrations of total protein (TP),interleukin-8(IL-8),tumor necrosis factor(TNF-α),the activities of elastase-like and α1-AT,total phospholipids(TPL) and disaturated phosphatidylcholine (DSPC).In addition,the wet-to-dry lung weight ratio(W/D) was measured. Results After infusion of endotoxin,it was observed that PaO2,peripheral luekocyte counts,total respiratory compliance progressively decreased and Ppeak and Qs/Qt increased comparing with the baseline values.In contrast to group NS,the increased plasma concentration but reduced activity of α1-AT was found in group LPS.In the BALF,the activity of α1-AT,TPL,DSPC/TPL were lower,but the concentrations of albumin,IL-8,TNF-α,and the activity of NE were higher.The ratio of W/D also increased.The pretreatment of α1-AT attenuated the deterioration of oxygenation,the reduction of compliance and the deterioration of other physiological,biochemical parameters mentioned above. Conclusion Pretreatment with α1-AT could attenuate endotoxin-induced lung injury in rabbits.Those beneficial effects of α1-AT might be due in part to the inhibitory effect on neutrophil elastase.

  15. Picrasma quassiodes (D. Don) Benn. attenuates lipopolysaccharide (LPS)-induced acute lung injury.

    Science.gov (United States)

    Lee, Jae-Won; Park, Ji-Won; Shin, Na-Rae; Park, So-Yeon; Kwon, Ok-Kyoung; Park, Hyun Ah; Lim, Yourim; Ryu, Hyung Won; Yuk, Heung Joo; Kim, Jung Hee; Oh, Sei-Ryang; Ahn, Kyung-Seop

    2016-09-01

    Picrasma quassiodes (D.Don) Benn. (PQ) is a medicinal herb belonging to the family Simaroubaceae and is used as a traditional herbal remedy for various diseases. In this study, we evaluated the effects of PQ on airway inflammation using a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) and LPS-stimulated raw 264.7 cells. ALI was induced in C57BL/6 mice by the intranasal administration of LPS, and PQ was administered orally 3 days prior to exposure to LPS. Treatment with PQ significantly attenuated the infiltration of inflammatory cells in the bronchoalveolar lavage fluid (BALF). PQ also decreased the production of reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BALF. In addition, PQ inhibited airway inflammation by reducing the expression of inducible nitric oxide synthase (iNOS) and by increasing the expression of heme oxygenase-1 (HO-1) in the lungs. Furthermore, we demonstrated that PQ blocked the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in the lungs of mice with LPS-induced ALI. In the LPS-stimulated RAW 264.7 cells, PQ inhibited the release of pro-inflammatory cytokines and increased the mRNA expression of monocyte chemoattractant protein-1 (MCP-1). Treatment with PQ decreased the translocation of nuclear factor (NF)-κB to the nucleus, and increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of HO-1. PQ also inhibited the activation of p38 in the LPS-stimulated RAW 264.7 cells. Taken together, our findings demonstrate that PQ exerts anti-inflammatory effects against LPS-induced ALI, and that these effects are associated with the modulation of iNOS, HO-1, NF-κB and MAPK signaling. Therefore, we suggest that PQ has therapeutic potential for use in the treatment of ALI. PMID:27431288

  16. Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways

    OpenAIRE

    Shuang Peng; Nan Hang; Wen Liu; Wenjie Guo; Chunhong Jiang; Xiaoling Yang; Qiang Xu; Yang Sun

    2016-01-01

    Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)...

  17. Plantamajoside ameliorates lipopolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation.

    Science.gov (United States)

    Wu, Haichong; Zhao, Gan; Jiang, Kangfeng; Chen, Xiuying; Zhu, Zhe; Qiu, Changwei; Li, Chengye; Deng, Ganzhen

    2016-06-01

    Despite developments in the knowledge and therapy of acute lung injury in recent decades, mortality remains high, and there is usually a lack of effective therapy. Plantamajoside, a major ingredient isolated from Plantago asiatica L. (Plantaginaceae), has been reported to have potent anti-inflammatory properties. However, the effect of plantamajoside on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice has not been investigated. The present study aimed to reveal the potential mechanism responsible for the anti-inflammatory effects of plantamajoside on LPS-induced acute lung injury in mice and in RAW264.7 cells. The results of histopathological changes as well as the lung wet-to-dry ratio and myeloperoxidase (MPO) activity showed that plantamajoside ameliorated the lung injury that was induced by LPS. qPCR and ELISA assays demonstrated that plantamajoside suppressed the production of IL-1β, IL-6 and TNF-α in a dose-dependent manner. TLR4 is an important sensor in LPS infection. Molecular studies showed that the expression of TLR4 was inhibited by plantamajoside administration. Further study was conducted on nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) using pathways using western blots. The results showed that plantamajoside inhibited the phosphorylation of IκBα, p65, p38, JNK and ERK. All results indicated that plantamajoside has protective effect on LPS-induced ALI in mice and in RAW264.7 cells. Thus, plantamajoside may be a potential therapy for the treatment of pulmonary inflammation.

  18. Plantamajoside ameliorates lipopolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation.

    Science.gov (United States)

    Wu, Haichong; Zhao, Gan; Jiang, Kangfeng; Chen, Xiuying; Zhu, Zhe; Qiu, Changwei; Li, Chengye; Deng, Ganzhen

    2016-06-01

    Despite developments in the knowledge and therapy of acute lung injury in recent decades, mortality remains high, and there is usually a lack of effective therapy. Plantamajoside, a major ingredient isolated from Plantago asiatica L. (Plantaginaceae), has been reported to have potent anti-inflammatory properties. However, the effect of plantamajoside on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice has not been investigated. The present study aimed to reveal the potential mechanism responsible for the anti-inflammatory effects of plantamajoside on LPS-induced acute lung injury in mice and in RAW264.7 cells. The results of histopathological changes as well as the lung wet-to-dry ratio and myeloperoxidase (MPO) activity showed that plantamajoside ameliorated the lung injury that was induced by LPS. qPCR and ELISA assays demonstrated that plantamajoside suppressed the production of IL-1β, IL-6 and TNF-α in a dose-dependent manner. TLR4 is an important sensor in LPS infection. Molecular studies showed that the expression of TLR4 was inhibited by plantamajoside administration. Further study was conducted on nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) using pathways using western blots. The results showed that plantamajoside inhibited the phosphorylation of IκBα, p65, p38, JNK and ERK. All results indicated that plantamajoside has protective effect on LPS-induced ALI in mice and in RAW264.7 cells. Thus, plantamajoside may be a potential therapy for the treatment of pulmonary inflammation. PMID:27089391

  19. Interleukin-1α drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD.

    Science.gov (United States)

    Osei, Emmanuel T; Noordhoek, Jacobien A; Hackett, Tillie L; Spanjer, Anita I R; Postma, Dirkje S; Timens, Wim; Brandsma, Corry-Anke; Heijink, Irene H

    2016-08-01

    Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial-mesenchymal interactions resulting in inflammatory and remodelling processes. We developed a co-culture model using COPD and control-derived airway epithelial cells (AECs) and lung fibroblasts to understand the mediators that are involved in remodelling and inflammation in COPD.AECs and fibroblasts obtained from COPD and control lung tissue were grown in co-culture with fetal lung fibroblast or human bronchial epithelial cell lines. mRNA and protein expression of inflammatory mediators, pro-fibrotic molecules and extracellular matrix (ECM) proteins were assessed.Co-culture resulted in the release of pro-inflammatory mediators interleukin (IL)-8/CXCL8 and heat shock protein (Hsp70) from lung fibroblasts, and decreased expression of ECM molecules (e.g. collagen, decorin) that was not different between control and COPD-derived primary cells. This pro-inflammatory effect was mediated by epithelial-derived IL-1α and increased upon epithelial exposure to cigarette smoke extract (CSE). When exposed to CSE, COPD-derived AECs elicited a stronger IL-1α response compared with control-derived airway epithelium and this corresponded with a significantly enhanced IL-8 release from lung fibroblasts.We demonstrate that, through IL-1α production, AECs induce a pro-inflammatory lung fibroblast phenotype that is further enhanced with CSE exposure in COPD, suggesting an aberrant epithelial-fibroblast interaction in COPD. PMID:27418555

  20. Developing novel therapeutic strategies for acute lung injury and infection-peripheral blood monocyte depletion and prophylactic antimicrobial therapy

    OpenAIRE

    Dhaliwal, Kanwaldeep

    2013-01-01

    BACKGROUND Acute lung injury (ALI) and nosocomial pneumonia are major causes of morbidity and mortality. There are 200,000 cases per year of ALI in the US with a mortality of 40%. On the intensive care unit (ICU), ALI accounts for over 40% of all ventilated patients at any one time. Despite this huge burden on healthcare and the relatively high prevalence, no therapies currently exist in clinical practice that attenuate the condition. The pathophysiology and aetiology of ALI is...

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

    OpenAIRE

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

    2016-01-01

    Acute lung injury, including impaired alveolar fluid clearance, is a life-threatening complication of severe respiratory virus infection, and effective treatment is lacking. Understanding the mechanism of this complication may suggest novel therapies. Here, we found that, in vitro, influenza A/H5N1 infection impaired alveolar fluid clearance more than did seasonal virus, mimicking its greater severity in patients. We demonstrated that this impairment is mediated by the release of soluble fact...

  2. Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats

    OpenAIRE

    Li Jianjun; Li Dong; Liu Xiaomei; Tang Shuhai; Wei Fengcai

    2012-01-01

    Abstract Background Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties and simultaneously lack the ability to illicit immune responses. Hence, MSCs have emerged as a promising candidate for cellular therapeutics for inflammatory diseases. Within the context of this study, we investigated whether human umbilical cord-derived mesenchymal stem cells (UC-MSCs) could ameliorate lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in a rat model. Methods ALI was induced ...

  3. Acute myocardial infarction mimicking squamous cell lung cancer with bone metastases due to hypercalcemia: a case report

    Institute of Scientific and Technical Information of China (English)

    FANG Chong-feng; XU Geng; CHEN Yang-xin

    2010-01-01

    @@ Acute myocardial infarction (AMI), the most severe coronary artery disease, is one of the most frequent cardiac emergencies, and early diagnosis and treatment are very important to decrease the subsequent cardiac adverse events such as malignant arrhythmia and sudden cardiac death. But in fact, lots of diseases are similar to AMI in clinical practice, of which the most common are myocarditis, pulmonary embolism in department of cardiology. Here we report a case of AMI-like squamous cell lung cancer with bone metastases.

  4. Multiple Inhibitory Pathways Contribute to Lung CD8+ T Cell Impairment and Protect against Immunopathology during Acute Viral Respiratory Infection.

    Science.gov (United States)

    Erickson, John J; Rogers, Meredith C; Tollefson, Sharon J; Boyd, Kelli L; Williams, John V

    2016-07-01

    Viruses are frequent causes of lower respiratory infection (LRI). Programmed cell death-1 (PD-1) signaling contributes to pulmonary CD8(+) T cell (TCD8) functional impairment during acute viral LRI, but the role of TCD8 impairment in viral clearance and immunopathology is unclear. We now find that human metapneumovirus infection induces virus-specific lung TCD8 that fail to produce effector cytokines or degranulate late postinfection, with minimally increased function even in the absence of PD-1 signaling. Impaired lung TCD8 upregulated multiple inhibitory receptors, including PD-1, lymphocyte activation gene 3 (LAG-3), T cell Ig mucin 3, and 2B4. Moreover, coexpression of these receptors continued to increase even after viral clearance, with most virus-specific lung TCD8 expressing three or more inhibitory receptors on day 14 postinfection. Viral infection also increased expression of inhibitory ligands by both airway epithelial cells and APCs, further establishing an inhibitory environment. In vitro Ab blockade revealed that multiple inhibitory receptors contribute to TCD8 impairment induced by either human metapneumovirus or influenza virus infection. In vivo blockade of T cell Ig mucin 3 signaling failed to enhance TCD8 function or reduce viral titers. However, blockade of LAG-3 in PD-1-deficient mice restored TCD8 effector functions but increased lung pathology, indicating that LAG-3 mediates lung TCD8 impairment in vivo and contributes to protection from immunopathology during viral clearance. These results demonstrate that an orchestrated network of pathways modifies lung TCD8 functionality during viral LRI, with PD-1 and LAG-3 serving prominent roles. Lung TCD8 impairment may prevent immunopathology but also contributes to recurrent lung infections. PMID:27259857

  5. Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats

    Directory of Open Access Journals (Sweden)

    Li Jianjun

    2012-09-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs possess potent immunomodulatory properties and simultaneously lack the ability to illicit immune responses. Hence, MSCs have emerged as a promising candidate for cellular therapeutics for inflammatory diseases. Within the context of this study, we investigated whether human umbilical cord-derived mesenchymal stem cells (UC-MSCs could ameliorate lipopolysaccharide- (LPS- induced acute lung injury (ALI in a rat model. Methods ALI was induced via injection of LPS. Rats were divided into three groups: (1 saline group(control, (2 LPS group, and (3 MSC + LPS group. The rats were sacrificed at 6, 24, and 48 hours after injection. Serum, bronchoalveolar lavage fluid (BALF, and lungs were collected for cytokine concentration measurements, assessment of lung injury, and histology. Results UC-MSCs increased survival rate and suppressed LPS-induced increase of serum concentrations of pro-inflammatory mediators TNF-α, IL-1β, and IL-6 without decreasing the level of anti-inflammatory cytokine IL-10. The MSC + LPS group exhibited significant improvements in lung inflammation, injury, edema, lung wet/dry ratio, protein concentration, and neutrophil counts in the BALF, as well as improved myeloperoxidase (MPO activity in the lung tissue. Furthermore, UC-MSCs decreased malondialdehyde (MDA production and increased Heme Oxygenase-1 (HO-1 protein production and activity in the lung tissue. Conclusion UC-MSCs noticeably increased the survival rate of rats suffering from LPS-induced lung injury and significantly reduced systemic and pulmonary inflammation. Promoting anti-inflammatory homeostasis and reducing oxidative stress might be the therapeutic basis of UC-MSCs.

  6. Acute and subacute non-infectious lung diseases. Usefulness of HRCT for evaluation of activity especially in follow-up

    International Nuclear Information System (INIS)

    The purpose of this study was to survey the usefulness of high-resolution CT (HRCT) for the evaluation of activity in acute and subacute non-infectious diffuse infiltrative lung diseases before and after corticosteroid treatment. Sequential HRCT images and chest radiographs obtained before and after treatment were retrospectively evaluated in 33 patients with acute or subacute non-infectious diffuse infiltrative lung diseases. All these patients were histologically confirmed to have pulmonary Inflammation and to have responded to treatment with corticosteroid. Radiographic and CT scores were correlated with the degree of dyspnea and the results of arterial blood gas analysis using Spearman's rank-correlation coefficient. On follow-up HRCT, the profusion score of areas with increased attenuation was significantly correlated with arterial oxygen tension (PaO2) (p=.003, r=-.53) and the alveolar-arterial oxygen tension difference (AaDO2) (p=.001, r=.57). No other correlation was found after treatment. Nodular and linear opacities were more commonly seen on follow-up chest radiographs and HRCT images than on initial ones. HRCT is useful for the evaluation of disease activity in acute and subacute non-infectious infiltrative lung diseases before and after treatment if paying special attention to the profusion of ground-glass attenuation. Even if pretreatment HRCT has not been performed, posttreatment HRCT should be examined. (author)

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

    Science.gov (United States)

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

    2016-01-01

    Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM. PMID:26841848

  8. Formononetin inhibited the inflammation of LPS-induced acute lung injury in mice associated with induction of PPAR gamma expression.

    Science.gov (United States)

    Ma, Zhanqiang; Ji, Weiwei; Fu, Qiang; Ma, Shiping

    2013-12-01

    Formononetin has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of formononetin in acute lung injury induced by lipopolysaccharide (LPS) in mice. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and IL-6,were assayed by enzyme-linked immunosorbent assay method. Pathological changes of hung tissues were observed by HE staining. Peroxisome proliferator-activated receptor (PPAR)-γ gene expression was measured by real-time PCR. The data showed that treatment with the formononetin group markedly attenuated inflammatory cell numbers in the BALF, increased PPAR-γ gene expression and improved SOD activity and inhibited MPO activity. The histological changes of the lungs were also significantly improved by formononetin compared to LPS group. The results indicated that formononetin has a protective effect on LPS-induced acute lung injury in mice. PMID:23907652

  9. Role of Complement C5 in Experimental Blunt Chest Trauma-Induced Septic Acute Lung Injury (ALI)

    Science.gov (United States)

    Karbach, Michael; Braumueller, Sonja; Kellermann, Philipp; Gebhard, Florian; Huber-Lang, Markus; Perl, Mario

    2016-01-01

    Background Severe blunt chest trauma is associated with high mortality. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS). In septic patients with ARDS complement activation products were found to be elevated in the plasma. In single models like LPS or trauma complement has been studied to some degree, however in clinically highly relevant double hit models such as the one used here little data is available. Here, we hypothesized that absence of C5 is correlated with a decreased inflammatory response in trauma induced septic acute lung injury. Methods 12 hrs after DH in mice the local and systemic cytokines and chemokines were quantified by multiplex bead array or ELISA, activated caspase-3 by western blot. Data were analyzed using one-way ANOVA followed by post-hoc Sidak’s multiple comparison test (significance, p≤ 0.05). Results In lung tissue interleukin (IL)-6, monocyte chemo attractant protein-1 (MCP-1) and granulocyte-colony stimulating factor (G-CSF) was elevated in both C5-/- mice and wildtype littermates (wt), whereas caspase-3 was reduced in lungs after DH in C5-/- mice. Systemically, reduced keratinocyte-derived chemokine (KC) levels were observed after DH in C5-/- compared to wt mice. Locally, lung myeloperoxidase (MPO), protein, IL-6, MCP-1 and G-CSF in brochoalveolar lavage fluid (BALF) were elevated after DH in C5-/- compared to wt. Conclusions In the complex but clinically relevant DH model the local and systemic inflammatory immune response features both, C5-dependent and C5-independent characteristics. Activation of caspase-3 in lung tissue after DH was C5-dependent whereas local inflammation in lung tissue was C5-independent. PMID:27437704

  10. Screening of multiparous women to avoid transfusion-related acute lung injury: a single centre experience.

    Science.gov (United States)

    Sachs, U J H; Link, E; Hofmann, C; Wasel, W; Bein, G

    2008-12-01

    The aim of this study was to investigate which approach for serological testing of multiparous donors might be feasible and effective to reduce the risk of transfusion-related acute lung injury (TRALI). TRALI is a serious adverse event of blood transfusion. Antibodies to granulocytes and human leucocyte antigens (HLAs) are frequently detected in sera of implicated donors. These donors are often multiparous women. A general deferral of female plasma or screening strategies for leucocyte antibodies has been proposed to increase blood safety. A prospective study was initiated in 2003. Until 2006, serum samples from all female donors reporting three or more pregnancies (n = 229) were screened for the presence of antibodies against granulocytes and HLAs by immunofluorescence and agglutination tests as well as by a commercial HLA enzyme immunoassay. In total, 40% of all multiparous women were reactive in one of the assays. Twenty-nine percent of the reactive sera contained antibodies to granulocytes but not to HLAs. During the observation period, three TRALI reactions occurred in our hospital, two of which would have been prevented if the screening program had been extended to all previously pregnant donors. We conclude from these data that, not unexpectedly, the number of previous pregnancies is not a reliable indicator for the likelihood of inducing TRALI. More importantly, screening strategies for antibodies that might induce TRALI should probably not be reduced to HLA antibody screening. This finding awaits further research. PMID:19140817

  11. The approach taken to reducing the risk of transfusion related acute lung injury in Canada.

    Science.gov (United States)

    Growe, G H; Petraszko, T R; Bigham, Mark

    2008-07-01

    Transfusion related acute lung injury (TRALI) has become a major reported cause of severe transfusion reactions and mortality. Over the past four years significant changes have been taken in Canada in order both to improve the recognition of the risk and to decrease its incidence. An international meeting was held in April of 2004 entitled "Towards an Understanding of TRALI". As a result of the analysis and recommendations from this meeting, the Canadian Blood Services established an ongoing review committee and established a laboratory diagnostic facility to identify at risk donors and recipients. A system has been developed to identify implicated donors and exclude them from the blood donor pool. Other steps have been taken to exclude potentially high risk donors, such as previously pregnant females, from the plasma and platelet donor pool. A considerable amount of education also has been offered to clinical services in the country. This paper summarizes the definitions, categorizations of implicated donors, and the ongoing precautionary activities related to plasma products. Noted within the article are the methods used for locating and selecting data. These were primarily based on the international TRALI conference in 2004, and from ongoing discussions and information provided by the Canadian Blood Services TRALI Review Committee. No ethics referral or approval was requested, and a summary is included in the article. PMID:20041083

  12. The approach taken to reducing the risk of transfusion related acute lung injury in Canada

    Directory of Open Access Journals (Sweden)

    Growe G

    2008-01-01

    Full Text Available Transfusion related acute lung injury (TRALI has become a major reported cause of severe transfusion reactions and mortality. Over the past four years significant changes have been taken in Canada in order both to improve the recognition of the risk and to decrease its incidence. An international meeting was held in April of 2004 entitled "Towards an Understanding of TRALI". As a result of the analysis and recommendations from this meeting, the Canadian Blood Services established an ongoing review committee and established a laboratory diagnostic facility to identify at risk donors and recipients. A system has been developed to identify implicated donors and exclude them from the blood donor pool. Other steps have been taken to exclude potentially high risk donors, such as previously pregnant females, from the plasma and platelet donor pool. A considerable amount of education also has been offered to clinical services in the country. This paper summarizes the definitions, categorizations of implicated donors, and the ongoing precautionary activities related to plasma products. Noted within the article are the methods used for locating and selecting data. These were primarily based on the international TRALI conference in 2004, and from ongoing discussions and information provided by the Canadian Blood Services TRALI Review Committee. No ethics referral or approval was requested, and a summary is included in the article.

  13. Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction

    OpenAIRE

    O'Mahony, D. Shane; Liles, W. Conrad; William A Altemeier; Dhanireddy, Shireesha; Frevert, Charles W.; Liggitt, Denny; Martin, Thomas R.; Matute-Bello, Gustavo

    2006-01-01

    Introduction Multiple organ dysfunction syndrome (MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunctio...

  14. Reassessment of inhaled nitric oxide in acute lung injury%重新评价吸入一氧化氮在急性肺损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    Frostell CG

    2003-01-01

    Inhaled nitric oxide (iNO) has now been used clinically since 1991, or twelve years. The acute aims of therapy have mainly been improvement of oxygenation and reduction of lung vasoconstriction. This is true also for the use in ALl (acute lung injury) of various degrees of severity including ARDS (acute respiratorydistress syndrome).

  15. 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.

  16. Effects of short-term propofol and dexmedetomidine on pulmonary morphofunction and biological markers in experimental mild acute lung injury.

    Science.gov (United States)

    Cavalcanti, Vinícius; Santos, Cintia Lourenço; Samary, Cynthia Santos; Araújo, Mariana Neves; Heil, Luciana Boavista Barros; Morales, Marcelo Marcos; Silva, Pedro Leme; Pelosi, Paolo; Fernandes, Fatima Carneiro; Villela, Nivaldo; Rocco, Patricia Rieken Macedo

    2014-11-01

    We evaluated whether the short-term use of dexmedetomidine and propofol may attenuate inflammatory response and improve lung morphofunction in experimental acute lung injury (ALI). Thirty-six Wistar rats were randomly divided into five groups. Control (C) and ALI animals received sterile saline solution and Escherichia coli lipopolysaccharide by intraperitoneal injection respectively. After 24h, ALI animals were randomly treated with dexmedetomidine, propofol, or thiopental sodium for 1h. Propofol reduced static lung elastance and resistive pressure and was associated with less alveolar collapse compared to thiopental sodium and dexmedetomidine. Dexmedetomidine improved oxygenation, but did not modify lung mechanics or histology. Propofol was associated with lower IL (interleukin)-6 and IL-1β expression, whereas dexmedetomidine led to reduced inducible nitric oxide (iNOS) and increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression in lung tissue compared to thiopental sodium. In conclusion, in this model of mild ALI, short-term use of dexmedetomidine and propofol led to different functional effects and activation of biological markers associated with pulmonary inflammation. PMID:25149586

  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. Clinical effects of continuous high volume hemofiltration on severe acute pancreatitis complicated with multiple organ dysfunction syndrome

    Institute of Scientific and Technical Information of China (English)

    Hao Wang; Wei-Qin Li; Wei Zhou; Ning Li; Jie-Shou Li

    2003-01-01

    AIM: To investigate the efficiency of continuous high volume hemofiltration (HVHF) in the treatment of severe acute pancreatitis (SAP) complicated with multiple organ dysfunction syndrome (MODS).METHODS: A total of 28 SAP patients with an average of 14.36±3.96 APACHE Ⅱ score were involved. Diagnostic criteria for SAP standardized by the Chinese Medical Association and diagnostic criteria for MODS standardized by American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM) were applied for inclusion. HVHF was started 6.0±6.1 (1-30) days after onset of the disease and sustained for at least 72 hours, AN69 hemofilter (1.2 m2)was changed every 24 hours. The ultrafiltration rate during HVHF was 4 000 mi/h, blood flow rate was 250-300 mi/min,and the substitute fluid was infused with pre-dilution. Low molecular weight heparin was used for anticoagulation.RESULTS: HVHF was well tolerated in all the patients, and lasted for 4.04±3.99 (3-24) days. 20 of the patients survived,6 patients died and 2 of the patients quited for financial reason.The ICU mortality was 21.4%. Body temperature, heart rate and breath rate decreased significantly after HVHF.APACHE Ⅱ score was 14.4±3.9 before HVHF, and 9.9±4.3after HVHF, which decreased significantly (P<0.01). Partial pressure of oxygen in arterial blood before HVHF was 68.5±19.5 mmHg, and increased significantly after HVHF,which was 91.9±25 mmHg (P<0.01). During HVHF the hemodynamics was stable, and serum potassium, sodium,chlorine, glucose and pH were at normal level.CONCLUSION: HVHF is technically possible in SAP patients complicated with MODS. It does not appear to have detrimental effects and may have beneficial effects.Continuous HVHF, which seldom disturbs the hemodynamics and causes few side-effects, is expected to become a beneficial adjunct therapy for SAP complicated with MODS.

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

    Science.gov (United States)

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

    2016-03-29

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation. PMID:26976597

  20. Understanding the function and dysfunction of the immune system in lung cancer:the role of immune checkpoints

    Institute of Scientific and Technical Information of China (English)

    Niki Karachaliou; Maria Gonzalez Cao; Cristina Teixid; Santiago Viteri; Daniela Morales-Espinosa; Mariacarmela Santarpia; Rafael Rosell

    2015-01-01

    AbstrAct Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis;a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite speciifcity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

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

    Directory of Open Access Journals (Sweden)

    Andrew S Brown

    2016-06-01

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

  2. 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

  3. Initial Sequential Organ Failure Assessment score versus Simplified Acute Physiology score to analyze multiple organ dysfunction in infectious diseases in Intensive Care Unit

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    Remyasri Nair

    2016-01-01

    Full Text Available Aims: To investigate initial Sequential Organ Failure Assessment (SOFA score of patients in Intensive Care Unit (ICU, who were diagnosed with infectious disease, as an indicator of multiple organ dysfunction and to examine if initial SOFA score is a better mortality predictor compared to Simplified Acute Physiology Score (SAPS. Materials and Methods: Hospital-based study done in medical ICU, from June to September 2014 with a sample size of 48. Patients aged 18 years and above, diagnosed with infectious disease were included. Patients with history of chronic illness (renal/hepatic/pulmonary/  cardiovascular, diabetes, hypertension, chronic obstructive pulmonary disease, heart disease, those on immunosuppressive therapy/chemoradiotherapy for malignancy and patients in immunocompromised state were excluded. Blood investigations were obtained. Six organ dysfunctions were assessed using initial SOFA score and graded from 0 to 4. SAPS was calculated as the sum of points assigned to each of the 17 variables (12 physiological, age, type of admission, and three underlying diseases. The outcome measure was survival status at ICU discharge. Results: We categorized infectious diseases into dengue fever, leptospirosis, malaria, respiratory tract infections, and others which included undiagnosed febrile illness, meningitis, urinary tract infection and gastroenteritis. Initial SOFA score was both sensitive and specific; SAPS lacked sensitivity. We found no significant association between age and survival status. Both SAPS and initial SOFA score were found to be statistically significant as mortality predictors. There is significant association of initial SOFA score in analyzing organ dysfunction in infectious diseases (P < 0.001. SAPS showed no statistical significance. There was statistically significant (P = 0.015 percentage of nonsurvivors with moderate and severe dysfunction, based on SOFA score. Nonsurvivors had higher SAPS but was not statistically

  4. Regulation and repair of the alveolar-capillary barrier in acute lung injury.

    Science.gov (United States)

    Bhattacharya, Jahar; Matthay, Michael A

    2013-01-01

    Considerable progress has been made in understanding the basic mechanisms that regulate fluid and protein exchange across the endothelial and epithelial barriers of the lung under both normal and pathological conditions. Clinically relevant lung injury occurs most commonly from severe viral and bacterial infections, aspiration syndromes, and severe shock. The mechanisms of lung injury have been identified in both experimental and clinical studies. Recovery from lung injury requires the reestablishment of an intact endothelial barrier and a functional alveolar epithelial barrier capable of secreting surfactant and removing alveolar edema fluid. Repair mechanisms include the participation of endogenous progenitor cells in strategically located niches in the lung. Novel treatment strategies include the possibility of cell-based therapy that may reduce the severity of lung injury and enhance lung repair. PMID:23398155

  5. PAMAM Nanoparticles Promote Acute Lung Injury by Inducing Autophagic Cell Death through the Akt-TSC2-mTOR Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    Chenggang Li; Haolin Liu; Yang Sun; Hongliang Wang; Feng Guo; Shuan Rao; Jiejie Deng; Yanli Zhang; Yufa Miao; Chenying Guo; Jie Meng; Xiping Chen; Limin Li; Dangsheng Li; Haiyan Xu; Heng Wang; Bo Li; Chengyu Jiang

    2009-01-01

    Nanotechnology is an important and emerging industry with a projected annual market of around one trillion US dollars by 2011–2015. Concerns about the toxicity of nanomaterials in humans, however, have recently been raised. Although studies of nanoparticle toxicity have focused on lung disease the molecular link between nanoparticle exposure and lung injury remained unclear. In this report, we show that cationic Starburst polyamidoamine dendrimer (PAMAM), a class of nanomaterials that are being widely developed for clinical applications can induce acute lung injury in vivo. PAMAM triggers autophagic cell death by deregulating the Akt-TSC2-mTOR signaling pathway. The autophagy inhibitor 3-methyladenine rescued PAMAM dendrimer-induced cell death and ameliorated acute lung injury caused by PAMAM in mice. Our data provide a molecular explanation for nanoparticle-induced lung injury, and suggest potential remedies to address the growing concerns of nanotechnology safety.

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

    Science.gov (United States)

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

    2007-08-20

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

  7. Effect of N-Acetylcystein in ICU patients with acute lung injury requiring mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Mojtahed Zadeh

    2008-08-01

    Full Text Available "n Background: Acute lung injury (ALI is a pulmonary pathology occuring in context of infection, trauma, burn, and sepsis. Tissue injury and release of chemical mediators result in tissue damage and organ failure especially respiratory failure. Many therapeutic modalities including vitamin E, allopurinol, and N-acetylcystein (NAC have been used to decrease levels of inflammatory factors and to control and improve signs and symptoms. The antioxidant feature of NAC induces synthesis of glutathione- the scavenger of free radicals- and increase respiratory drive and PaO2. In time diagnosis of ALI, prompt institution of treatment will reduce mortality and morbidity in critical illness."n"nMethods: This open label analytical clinical trial included a total of 50 patients admitted in the ICU ward of Sina University Hospital. They were randomly divided into two groups of 25, the case group received NAC 150mg/kg in 100ml Normal saline within 20 minutes then 50mg/kg in 100ml Normal saline within 4 hr after that 50mg/kg daily for three days. The controls received only normal saline. Oxygenation and ventilation parameters were studied In both groups."n"nResults: There were no significant difference between the groups in terms of demographic indices, mean SpO2, ABG values, mortality rates, and clearing of chest x-rays. The best outcome was seen in young traumatic patients."n"nConclusion: In this relatively small group of patients presenting with an established ALI/ ARDS subsequent to a variety of underlying disease, intravenous NAC treatment during first four days neither significantly improved systemic oxygenation nor reduced the need for ventilatory support.

  8. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kwint, Margriet [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Uyterlinde, Wilma [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Heuvel, Michel van den [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Knegjens, Joost; Herk, Marcel van [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Belderbos, Jose, E-mail: j.belderbos@nki.nl [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  9. Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB.

    Directory of Open Access Journals (Sweden)

    Tao Zhu

    Full Text Available BACKGROUND: Nuclear factor-κB (NF-κB is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. METHODS AND RESULTS: In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. CONCLUSIONS: These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.

  10. Detection of the serum endothelin content in patients with acute lung injury and its value of severity evaluation

    Institute of Scientific and Technical Information of China (English)

    Yu-Fu Zhou; Bin Chen

    2016-01-01

    Objective: To observe the correlation of serum endothelin content in patients with acute radiation lung injury and with the degree of inflammatory reaction and the lung functional level. Methods: 68 Patients with non-small cell lung cancer who received the radiotherapy in treatment from May 2013 to October 2015 in our hospital were selected as the object of study. 25 patients who had acute radiation induced lung injury within 24 months of the radiotherapy were rolled in the radiation induced lung injury group (RILI group), and the rest of 43 without acute lung injury were rolled in the negative control group (NC group). The contents of endothelin, tumor necrosis factor a, interleukin-1b, interleukin-6 in serum and the partial pressure of oxygen in artery, partial pressure of carbon dioxide in artery, vital capacity, forced expiratory volume in one second, maximal ventilatory volume, and diffusion capacity for carbon monoxide were tested. Results: The content of serum endothelin of the patients in the RILI group [(69.3 ± 7.5) pg/mL] were all obviously higher than that of the NC group [(24.1 ± 2.9) pg/mL]; the content of the serum tumor necrosis factor a [(49.6 ± 5.1) ng/mL vs. (22.7 ± 3.1) ng/mL], interleukin-1b [(29.4 ± 3.3) ng/mL vs. (15.7 ± 1.8) ng/mL], interleukin-6 [(163.4 ± 20.3) pg/mL vs. (89.4 ± 10.2) pg/mL] and the partial pressure of carbon dioxide in artery [(49.2 ± 5.2) mmHg vs. (40.3 ± 4.8) mmHg] were all obviously higher than that of the NC group, which were positively correlated with the serum endothelin content. But the partial pressure of oxygen in artery [(68.4 ± 7.8) mmHg vs. (87.3 ± 9.5) mmHg], vital capacity [(1 203.4 ± 136.5) mL vs. (2 034.8 ± 238.5) mL], forced expiratory volume in one second [(38.4 ± 4.1)%vs. (58.3 ± 6.2)%], maximum minute ventilation [(33.7 ± 3.8) L/min vs. (66.1 ± 7.9) L/min] and diffusing capacity of the lungs for carbon monoxide [(79.3 ± 8.9)%vs. (86.7 ± 9.4)%)] were obviously lower than that of the NC

  11. Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

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    Velat Şen

    2014-01-01

    Full Text Available The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI was found to be associated with increased malondialdehyde (MDA, total oxidant activity (TOA, oxidative stress index (OSI, and decreased total antioxidant capacity (TAC. Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P<0.05. The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

  12. Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

    Science.gov (United States)

    Sen, Velat; Güzel, Abdulmenap; Şen, Hadice Selimoğlu; Ece, Aydın; Uluca, Unal; Söker, Sevda; Doğan, Erdal; Kaplan, İbrahim; Deveci, Engin

    2014-01-01

    The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300-350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI. PMID:25165710

  13. Biphasic positive airway pressure minimizes biological impact on lung tissue in mild acute lung injury independent of etiology

    OpenAIRE

    Saddy, Felipe; Moraes, Lillian; Santos, Cintia Lourenço; Oliveira, Gisele Pena; Cruz, Fernanda Ferreira; Morales, Marcelo Marcos; Capelozzi, Vera Luiza; de Abreu, Marcelo Gama; Baez Garcia, Cristiane Souza Nascimento; Pelosi, Paolo; Rocco, Patricia Rieken Macêdo

    2013-01-01

    Introduction Biphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assis...

  14. Acute abdomen due to spontaneous splenic rupture as the first presentation of lung malignancy: a case report

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    Arulraj Nolan

    2011-09-01

    Full Text Available Abstract Introduction Spontaneous splenic rupture is well recognized in the context of hematological malignancies (lymphoproliferative and myeloproliferative disorders; a few case reports have also linked solid tumors, such as pancreatic and liver cancer, with the occurrence of spontaneous splenic rupture. This is the first case report of lung cancer as a likely cause of spontaneous splenic rupture. Case presentation A 61-year-old Caucasian woman presented to our hospital with non-specific symptoms. She developed an 'acute' abdomen and went into a state of shock within twelve hours of her presentation. She was diagnosed with spontaneous splenic rupture with radiology and following a laparotomy. She made an uneventful recovery postoperatively and was simultaneously found to have a bronchial adenocarcinoma. Conclusion Spontaneous splenic rupture is a potentially fatal but often unrecognized cause of acute abdomen. It should be routinely considered in the differential diagnosis of acute ('surgical' abdomen and when present it should be promptly dealt with, most commonly with a laparotomy. Once the diagnosis is confirmed there should be an aggressive drive to identify an underlying etiology; malignancy is the commonest culprit. Solid tumors should be considered as underlying causes despite being less common than hematological neoplasms. This case report demonstrates lung malignancy as an underlying precipitating cause of spontaneous splenic rupture.

  15. Effect of TLR-4 and HO-1 on acute lung injury induced by hemorrhagic shock in mice

    Institute of Scientific and Technical Information of China (English)

    CHEN Chang; WANG Yan-lin; WANG Cheng-yao; ZHANG Zong-ze

    2008-01-01

    To examine whether TLR-4 has an effect on hemorrhage induced changes in lung,and to investigate the change of heine oxygenase-1(HO-1)on acute lung injury(ALI)induced by hemorrhagic shock in mice.Methods:Forty-eight mate mice,including C3H/HeN mice and C3H/HeJ mice, were randomly divided into sham group(n=12),hemorrhagic shock group with twelve mice in each phase. Blood pressure (BP) was monitored continuously by attaching carotid artery catheter to a strain gauge pressure transducer/ polygraph. Arterial blood samples were taken for blood gas analysis. A mouse model of non-lethal hemorrhagic shock and resuscitation was used to observe pulmonary myeloperoxidase(MPO)activity and wet/dry weight ratio (W/D). The expression of HO-1 was observed by means of RT-PCR and immunohistochemistry.IL-6 and IL-10 in lung tissue homogenate were assayed by enzyme-linked immunosorbent assay (ELISA). The pulmonary pathologic changes were observed under electron microscope and light microscope.Results:Compared with sham group,the expression of HO-1 in lung tissue was significantly higher in Hem 24 h and Hem 48 h of C3H/HeN mice(P<0.01).The expression of HO-1 mRNA and the levels of IL-6, IL-10 and MPO in lung tissue were markedly increased in Hem 24 h (P<0.01 or P<0.05);Compared with C3H/HeN mice, the expression of HO-1 mRNA and the levels of IL-6 and IL-10 in C3H/HeJ mice significantly decreased in Hem 24 h and Hem 48 h (p<0.01or P<0.05),and the W/D,MPO in C3H/HeJ mice were obviously lower in Hem 24 h(P<0.05).The injuries of lung tissues after hemorrhagic shock have been demonstrated by histological examination with electron microscope and light microscope.Conclusions:TLR-4 and HO-1 might modulate the balance of pro-and anti-inflammatory processes in inflammatory reaction of hemorrhagic shock-induced ALI, and the activation of Toll-like receptor might induce the transcription activity of HO-1,which may play a key role in acute lung injury.

  16. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs.

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    Rebecca Y Petersen

    Full Text Available Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP is being increasingly used clinically to transition preterm infants at birth.To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs.The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF, bronchoalveolar lavage fluid (BAL, right mainstem bronchi and peripheral lung tissue were evaluated for inflammation.Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used.Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.

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

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    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

  18. Angiotensin II is related to the acute aortic dissection complicated with lung injury through mediating the release of MMP9 from macrophages

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    Wu, Zhiyong; Ruan, Yongle; Chang, Jinxing; Li, Bowen; Ren, Wei

    2016-01-01

    Background: Acute aortic dissection (AAD) patients usually show concurrent lung injury mainly featured by hyoxemia. To date, no effective treatment method has been established for the AAD complicated with acute lung injury (ALI). Matrix metalloproteinases (MMPs), especially MMP2 and MMP9, have been considered to be closely related to the onset of aortic disease including AAD. To investigate the roles of MMP in the pathogenesis of AAD complicated with ALI, we determined the expression of MMP2 and MMP9 in serum and lung tissues of AAD patients. In addition, a new rat model of AAD complicated with ALI was established to investigate the pathogenesis of such complicated conditions. Methods and results: Angiotensin II (Ang II) and MMP9 were up-regulated in the AAD complicated with ALI patients compared to those of the AAD without ALI patients, normal individuals and the patients with non-ruptured aneurysm. Besides, massive macrophages with MMP9 expression was noticed in the lung tissues in the AAD complicated with ALI patients. On this basis, AAD complicated with ALI rat model was established based on BAPN feeding and infusion of Ang II. Obvious lung injury was observed in the BAPN+Ang II group compared to that of the BAPN group, together with macrophage accumulation in lung tissues, as well as over-expression of MMP9 in lung tissues. After interference of MMP antagonist, a large number of macrophages were still accumulated in the lung tissues, but the lung injury was obviously attenuated. After the interference of AT1 receptor, the number of macrophages in the lung tissues was obviously decreased and the lung injury was obviously relieved. Conclusions: Ang II is closely related to the lung injury at the early stage of AAD through mediating the release of MMP9 in the macrophages in the lung tissues. PMID:27186269

  19. Acute lung injury: How macrophages orchestrate resolution of inflammation and tissue repair

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    Susanne eHerold

    2011-11-01

    Full Text Available Lung macrophages are long living cells with broad differentiation potential, which reside in the lung interstitium and alveoli or are organ-recruited upon inflammatory stimuli. A role of resident and recruited macrophages in initiating and maintaining pulmonary inflammation in lung infection or injury has been convincingly demonstrated. More recent reports suggest that lung macrophages are main orchestrators of termination and resolution of inflammation and initiators of parenchymal repair processes that are essential for return to homeostasis with normal gas exchange. In this review we will discuss cellular cross-talk mechanisms and molecular pathways of macrophage plasticity which define their role in inflammation resolution and in initiation of lung barrier repair following lung injury.

  20. Current perspectives on antibody-mediated rejection after lung transplantation

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    Witt CA

    2014-10-01

    Full Text Available Chad A Witt, Ramsey R Hachem Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA Abstract: The role of donor-specific antibodies (DSA to human leukocyte antigens and the burden of antibody-mediated rejection (AMR in lung transplantation remain enigmatic. Over the past several years, evidence has been emerging that humoral immunity plays an important role in the development of both acute and chronic lung allograft dysfunction (CLAD. Multiple case reports and case series have identified lung allograft recipients with clinical findings consistent with acute AMR. However, there is currently no widely accepted definition for AMR in lung transplantation, and this has been a significant barrier to furthering our understanding of this form of rejection. Nonetheless, the development of DSA after transplantation has consistently been identified as an independent risk factor for persistent and high-grade acute cellular rejection and CLAD. This has raised the possibility that chronic AMR may be a distinct phenotype of CLAD although evidence supporting this paradigm is still lacking. Additionally, antibodies to lung-restricted self-antigens (collagen V and K-α 1 tubulin have been associated with primary graft dysfunction early and the development of CLAD late after transplantation, and emerging evidence underscores significant interactions between autoimmunity and alloimmunity after transplantation. There is currently an active International Society for Heart and Lung Transplantation working group that is developing an operational definition for AMR in lung transplantation. This will be critical to improve our understanding of this form of rejection and conduct clinical trials to identify optimal treatment strategies. This review will summarize the literature on DSA and AMR in lung transplantation and discuss the impact of antibodies to self-antigens on lung

  1. Changes in respiratory elastance after deep inspirations reflect surface film functionality in mice with acute lung injury.

    Science.gov (United States)

    Takahashi, Ayuko; Bartolák-Suki, Erzsébet; Majumdar, Arnab; Suki, Béla

    2015-08-01

    Pulmonary surfactant reduces surface tension in the lung and prevents alveolar collapse. Following a deep inspiration (DI), respiratory elastance first drops then gradually increases due to surface film and tissue viscoelasticity. In acute lung injury (ALI), this increase is faster and governed by alveolar collapse due to increased surface tension. We hypothesized that the rate of increase in elastance reflects the deficiency of surfactant in the lung. To test this, mice were ventilated before (baseline) and after saline lavage obtained by injecting 0.8 ml and withdrawing 0.7 ml fluid (severe ALI) or injecting 0.1 ml (mild ALI). After two DIs, elastance was tracked for 10 min followed by a full lavage to assess surfactant proteins B (SP-B) and C (SP-C) content. Following 2 DIs, the increases in elastance during 10 min ventilation (ΔH) were 3.60 ± 0.61, 5.35 ± 1.04, and 8.33 ± 0.84 cmH2O/ml in baseline mice and mice with mild and severe ALI, respectively (P surface film functionality in lavage-induced ALI in mice. This method could prove useful in clinical situations such as diagnosing surfactant problems, monitoring recovery from lung injury or the effectiveness of surfactant therapy. PMID:26066828

  2. Metabolomics Investigation Reveals Metabolite Mediators Associated with Acute Lung Injury and Repair in a Murine Model of Influenza Pneumonia

    Science.gov (United States)

    Cui, Liang; Zheng, Dahai; Lee, Yie Hou; Chan, Tze Khee; Kumar, Yadunanda; Ho, Wanxing Eugene; Chen, Jian Zhu; Tannenbaum, Steven R.; Ong, Choon Nam

    2016-01-01

    Influenza virus infection (IVI) can cause primary viral pneumonia, which may progress to acute lung injury (ALI) and respiratory failure with a potentially fatal outcome. At present, the interactions between host and influenza virus at molecular levels and the underlying mechanisms that give rise to IVI-induced ALI are poorly understood. We conducted a comprehensive mass spectrometry-based metabolic profiling of serum, lung tissue and bronchoalveolar lavage fluid (BALF) from a non-lethal mouse model with influenza A virus at 0, 6, 10, 14, 21 and 28 days post infection (dpi), representing the major stages of IVI. Distinct metabolite signatures were observed in mice sera, lung tissues and BALF, indicating the molecular differences between systematic and localized host responses to IVI. More than 100 differential metabolites were captured in mice sera, lung tissues and BALF, including purines, pyrimidines, acylcarnitines, fatty acids, amino acids, glucocorticoids, sphingolipids, phospholipids, etc. Many of these metabolites belonged to pulmonary surfactants, indicating IVI-induced aberrations of the pulmonary surfactant system might play an important role in the etiology of respiratory failure and repair. Our findings revealed dynamic host responses to IVI and various metabolic pathways linked to disease progression, and provided mechanistic insights into IVI-induced ALI and repair process. PMID:27188343

  3. After the chemotherapy: potential mechanisms for chemotherapy-induced delayed skeletal muscle dysfunction in survivors of acute lymphoblastic leukaemia in childhood

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    Celena eScheede-Bergdahl

    2013-04-01

    Full Text Available There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukaemia (ALL, have increased rates of longterm skeletal muscle dysfunction. This places them at higher risk of physical restriction and functional impairment as well as potentially contributing to observed increases in cardiovascular disease and insulin resistance in later life. The mechanisms underlying these changes in skeletal muscle are unknown but chemotherapy drugs used in treatment for ALL are strongly implicated. Normal skeletal muscle growth, development and function are dependent on correctly functioning muscle satellite cells, muscle motor neurons and muscle mitochondria. Each of these key components is potentially susceptible to damage by chemotherapy in childhood, particularly prolonged courses including repeated administration of combination chemotherapy. If this chemotherapy-induced damage is not fully reversible, impairment of satellite cells, muscle motor innervation and mitochondria could, either singly or together, lead to the emergence of delayed or persistent skeletal muscle dysfunction many years later. The known effects of individual drugs used in the treatment of ALL are outlined and the need for specific targeted studies to investigate the mechanisms underlying persistent muscle dysfunction in survivors of childhood cancers is highlighted.

  4. Cutting Edge: Acute Lung Allograft Rejection Is Independent of Secondary Lymphoid Organs1

    OpenAIRE

    Gelman, Andrew E.; Li, Wenjun; Richardson, Steven B.; Zinselmeyer, Bernd H.; Lai, Jiaming; Okazaki, Mikio; Kornfeld, Christopher G.; Kreisel, Friederike H.; Sugimoto, Seiichiro; Tietjens, Jeremy R.; Dempster, John; Patterson, G. Alexander; Krupnick, Alexander S.; Miller, Mark J.; Kreisel, Daniel

    2009-01-01

    It is the prevailing view that adaptive immune responses are initiated in secondary lymphoid organs. Studies using alymphoplastic mice have shown that secondary lymphoid organs are essential to initiate allograft rejection of skin, heart, and small bowel. The high immunogenicity of lungs is well recognized and allograft rejection remains a major contributing factor to poor outcomes after lung transplantation. We show in this study that alloreactive T cells are initially primed within lung all...

  5. Conflicting Physiological and Genomic Cardiopulmonary Effects of Recruitment Maneuvers in Murine Acute Lung Injury

    OpenAIRE

    Mekontso Dessap, Armand; Voiriot, Guillaume; Zhou, Tong; Marcos, Elisabeth; Dudek, Steven M.; Jacobson, Jeff R.; Machado, Roberto,; Adnot, Serge; Brochard, Laurent; Maitre, Bernard; Joe G N Garcia

    2012-01-01

    Low tidal volume ventilation, although promoting atelectasis, is a protective strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment maneuvers restore lung volumes, but potentially compromise lung parenchymal and vascular function via repetitive overdistention. Our objective was to examine cardiopulmonary physiological and transcriptional consequences of recruitment maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were placed on mechanical ven...

  6. Association of Toll-Like Receptor Signaling and Reactive Oxygen Species: A Potential Therapeutic Target for Posttrauma Acute Lung Injury

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    Meng Xiang

    2010-01-01

    Full Text Available Acute lung injury (ALI frequently occurs in traumatic patients and serves as an important component of systemic inflammatory response syndrome (SIRS. Hemorrhagic shock (HS that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response. Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs and interactions between neutrophils (PMNs and alveolar macrophages (AMϕ as well as endothelial cells (ECs, in which reactive oxygen species (ROS are the key mediator. This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.

  7. 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-

  8. 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.

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

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    Rector Edward S

    2004-11-01

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

  10. Metastasis-Induced Acute Pancreatitis Successfully Treated with Chemotherapy and Radiotherapy in a Patient with Small Cell Lung Cancer

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    Kerem Okutur

    2015-01-01

    Full Text Available Although involvement of pancreas is a common finding in small cell lung cancer (SCLC, metastasis-induced acute pancreatitis (MIAP is very rare. A 50-year-old female with SCLC who had limited disease and achieved full response after treatment presented with acute pancreatitis during her follow-up. The radiologic studies revealed a small area causing obliteration of the pancreatic duct without mass in the pancreatic neck, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA confirmed the metastasis of SCLC. The patient was treated successfully with systemic chemotherapy and radiotherapy delivered to pancreatic field. In SCLC, cases of MIAP can be encountered with conventional computed tomography with no mass image, and positron emission tomography and EUS-FNA can be useful for diagnosis of such cases. Aggressive systemic and local treatment can prolong survival, especially in patients with good performance status.

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

    Science.gov (United States)

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

    2013-06-01

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

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

    International Nuclear Information System (INIS)

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

  13. Feasibility of (68)Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome.

    Science.gov (United States)

    Retamal, Jaime; Sörensen, Jens; Lubberink, Mark; Suarez-Sipmann, Fernando; Borges, João Batista; Feinstein, Ricardo; Jalkanen, Sirpa; Antoni, Gunnar; Hedenstierna, Göran; Roivainen, Anne; Larsson, Anders; Velikyan, Irina

    2016-01-01

    There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [(15)O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting (68)Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([(68)Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [(68)Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [(68)Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [(68)Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion. PMID:27069763

  14. Transcriptional profiling at different sites in lungs of pigs during acute bacterial respiratory infection

    DEFF Research Database (Denmark)

    Mortensen, Shila; Skovgaard, Kerstin; Hedegaard, Jakob;

    2011-01-01

    The local transcriptional response was studied in different locations of lungs from pigs experimentally infected with the respiratory pathogen Actinobacillus pleuropneumoniae serotype 5B, using porcine cDNA microarrays. This infection gives rise to well-demarcated infection loci in the lung......, characterized by necrotic and haemorrhagic lesions. Lung tissue was sampled from necrotic areas, from visually unaffected areas and from areas bordering on necrotic areas. Expression pattern of these areas from infected pigs was compared to healthy lung tissue from un-infected pigs. Transcription of selected...... genes important in the innate defence response were further analysed by quantitative realtime reverse-transcriptase PCR. A clear correlation was observed between the number of differentially expressed genes as well as the magnitude of their induction and the sampling location in the infected lung...

  15. Usefulness of a selective neutrophil elastase inhibitor, sivelestat, in acute lung injury patients with sepsis

    Directory of Open Access Journals (Sweden)

    Miyoshi S

    2013-04-01

    Full Text Available Seigo Miyoshi,1 Hironobu Hamada,1,2 Ryoji Ito,1 Hitoshi Katayama,1 Kazunori Irifune,1 Toshimitsu Suwaki,3 Norihiko Nakanishi,4 Takanori Kanematsu,5 Kentaro Dote,6 Mayuki Aibiki,7 Takafumi Okura,1 Jitsuo Higaki1 1Department of Integrated Medicine and Informatics, Ehime University, Graduate School of Medicine, Toon, 2Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 3Department of Respiratory Medicine, Sumitomo Besshi Hospital, Niihama, 4Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, 5Department of Respiratory Medicine, Matsuyama Red Cross Hospital, Matsuyama, 6Intensive Care Division, Ehime University Hospital, Toon, 7Department of Emergency Medicine, School of Medicine, Ehime University, Toon, Japan Background: Neutrophil elastase plays a crucial role in the development of acute lung injury (ALI in patients with systemic inflammatory response syndrome (SIRS. The clinical efficacy of the neutrophil elastase inhibitor, sivelestat, for patients with ALI associated with SIRS has not been convincingly demonstrated. The aim of this study was to determine if there are clinical features of patients with this condition that affect the efficacy of sivelestat. Methods: This was a retrospective study of 110 ALI patients with SIRS. Clinical information, including the etiology of ALI, the number of organs failing, scoring systems for assessing the severity of illness, and laboratory data, was collected at the time of diagnosis. Information on the number of ventilator-free days (VFDs and changes in PaO2/FIO2 (ΔP/F before and 7 days after the time of ALI diagnosis was also collected. The effect of sivelestat on ALI patients was also examined based on whether they had sepsis and whether their initial serum procalcitonin level was ≥0.5 ng/mL. Results: There were 70 patients who were treated with sivelestat and 40 control patients. VFDs and ΔP/F were significantly higher in the treated

  16. Effect of penehyclidine hydrochloride on patients with acute lung injury and its mechanisms

    Institute of Scientific and Technical Information of China (English)

    LI Bai-qiang; SUN Hai-chen; NIE Shi-nan; SHAO Dan-bing; LIU Hong-mei; QIAN Xiao-ming

    2010-01-01

    Objective: To assess the effects of penehyclidine hydrochloride on patients with acute lung injury (ALI), to observe the expression of Toll-like receptor 4 (TLR4) on the peripheral monocytes of ALI patients and changes of inflammatory & anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI.Methods: Forty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group (P group, n=21) and conventional treatment group (control group, C group, n=24). Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride (1 mg, im, q. 12 h) in addition.The TLR4 expression of 20 healthy volunteers were detected.The clinical effect, average length of stay in ICU and hospital,values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h.Results: The general conditions of the two groups were improved gradually and PaO2 increased progressively.Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased (P<0.05). The improvement in P group was obviously greater than that in C group (P<0.05). The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU (t=3.485, P<0.01). The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers (P<0.01). It decreased significantly at 24 h (t=2.032, P<0.05) and 48 h (t=3.620, P<0.01)and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome (ARDS). The incidence of ARDS was 23.8% in P group and 29

  17. LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing.

    Directory of Open Access Journals (Sweden)

    Sophie Seehase

    Full Text Available Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS-induced inflammation model was established in marmoset monkeys (Callithrix jacchus to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4 inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α and macrophage inflammatory protein-1 beta (MIP-1β were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-α, and MIP-1β. TNF-α release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-α secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC(50. LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-α and MIP-1β levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.

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

    Directory of Open Access Journals (Sweden)

    Ailan Zhang

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

  19. Staphylococcal enterotoxin B-induced microRNA-155 targets SOCS1 to promote acute inflammatory lung injury.

    Science.gov (United States)

    Rao, Roshni; Rieder, Sadiye Amcaoglu; Nagarkatti, Prakash; Nagarkatti, Mitzi

    2014-07-01

    Staphylococcal enterotoxin B (SEB) causes food poisoning in humans. It is considered a biological weapon, and inhalation can trigger lung injury and sometimes respiratory failure. Being a superantigen, SEB initiates an exaggerated inflammatory response. While the role of microRNAs (miRNAs) in immune cell activation is getting increasing recognition, their role in the regulation of inflammatory disease induced by SEB has not been studied. In this investigation, we demonstrate that exposure to SEB by inhalation results in acute inflammatory lung injury accompanied by an altered miRNA expression profile in lung-infiltrating cells. Among the miRNAs that were significantly elevated, miR-155 was the most overexpressed. Interestingly, miR-155(-/-) mice were protected from SEB-mediated inflammation and lung injury. Further studies revealed a functional link between SEB-induced miR-155 and proinflammatory cytokine gamma interferon (IFN-γ). Through the use of bioinformatics tools, suppressor of cytokine signaling 1 (SOCS1), a negative regulator of IFN-γ, was identified as a potential target of miR-155. While miR-155(-/-) mice displayed increased expression of Socs1, the overexpression of miR-155 led to its suppression, thereby enhancing IFN-γ levels. Additionally, the inhibition of miR-155 resulted in restored Socs1expression. Together, our data demonstrate an important role for miR-155 in promoting SEB-mediated inflammation in the lungs through Socs1 suppression and suggest that miR-155 may be an important target in preventing SEB-mediated inflammation and tissue injury. PMID:24778118

  20. PARP-1 inhibitor, DPQ, attenuates LPS-induced acute lung injury through inhibiting NF-κB-mediated inflammatory response.

    Directory of Open Access Journals (Sweden)

    Gang Wang

    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. Poly (ADP-ribose polymerase-1 has been demonstrated to be involved in tissue inflammation and one of its inhibitors, 3, 4-Dihydro-5[4-(1-piperindinylbutoxy]-1(2H-isoquinoline (DPQ, exerts anti-inflammatory effect. However, it is still unclear whether the DPQ possesses the protective effect on ALI and what mechanisms are involved. In this study, we tested the effect of DPQ on the lung inflammation induced by lipopolysaccharide (LPS challenge in mice. We found that 6 h-LPS challenge induced significant lung inflammation and vascular leakage in mice. Treatment with DPQ at the dose of 10 μg/kg markedly reduced the neutrophil infiltration, myeloperoxidase activity and up-regulation of pro-inflammatory mediators and cytokines. LPS-elevated vascular permeability was decreased by DPQ treatment, accompanied by the inhibition of apoptotic cell death in mice lungs. In addition, we isolated mice peritoneal macrophages and showed pretreatment with DPQ at 10 μM inhibited the production of cytokines in the macrophages following LPS stimulation. DPQ treatment also inhibited the phosphorylation and degradation of IκB-α, subsequently blocked the activation of nuclear factor (NF-κB induced by LPS in vivo and in vitro. Taken together, our results show that DPQ treatment inhibits NF-κB signaling in macrophages and protects mice against ALI induced by LPS, suggesting inhibition of Poly (ADP-ribose polymerase-1 may be a potential and effective approach to resolve inflammation for the treatment of ALI.

  1. 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.

  2. Pulmonary Specific Ancillary Treatment for Pediatric Acute Respiratory Distress Syndrome : Proceedings From the Pediatric Acute Lung Injury Consensus Conference

    NARCIS (Netherlands)

    Tamburro, Robert F.; Kneyber, Martin C. J.

    2015-01-01

    Objective: To provide an overview of the current literature on pulmonary-specific therapeutic approaches to pediatric acute respiratory distress syndrome to determine recommendations for clinical practice and/or future research. Data Sources: PubMed, EMBASE, CINAHL, SCOPUS, and the Cochrane Library

  3. Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day

  4. Cardiorespiratory effects of recruitment maneuvers and positive end expiratory pressure in an experimental context of acute lung injury and pulmonary hypertension

    OpenAIRE

    Doras, Camille; Le Guen, Morgan; Peták, Ferenc; Habre, Walid

    2015-01-01

    Background Recruitment maneuvers (RM) and positive end expiratory pressure (PEEP) are the cornerstone of the open lung strategy during ventilation, particularly during acute lung injury (ALI). However, these interventions may impact the pulmonary circulation and induce hemodynamic and respiratory effects, which in turn may be critical in case of pulmonary hypertension (PHT). We aimed to establish how ALI and PHT influence the cardiorespiratory effects of RM and PEEP. Methods Rabbits control o...

  5. Respiratory dysfunction and proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis.

    Science.gov (United States)

    Bonville, Cynthia A; Bennett, Nicholas J; Koehnlein, Melissa; Haines, Deborah M; Ellis, John A; DelVecchio, Alfred M; Rosenberg, Helene F; Domachowske, Joseph B

    2006-05-25

    We explore relationships linking clinical symptoms, respiratory dysfunction, and local production of proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis. With a reduced inoculum of this natural rodent pathogen, we observe virus clearance by day 9, while clinical symptoms and respiratory dysfunction persist through days 14 and 17 postinoculation, respectively. Via microarray and ELISA, we identify expression profiles of proinflammatory mediators MIP-1alpha, MCP-1, and MIP-2 that correlate with persistent respiratory dysfunction. MIP-1alpha is localized in bronchial epithelium, which is also the major site of PVM replication. Interferon-gamma was detected in lung tissue, but at levels that do not correlate with respiratory dysfunction. Taken together, we present a modification of our pneumovirus infection model that results in improved survival and data that stand in support of a connection between local production of specific mediators and persistent respiratory dysfunction in the setting of acute viral bronchiolitis.

  6. 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.

  7. Captopril pretreatment protects the lung against severe acute pancreatitis induced injury via inhibiting angiotensin II production and suppressing Rho/ROCK pathway.

    Science.gov (United States)

    Yu, Qi-Hong; Guo, Jie-Fang; Chen, Yan; Guo, Xiao-Rong; Du, Yi-Qi; Li, Zhao-Shen

    2016-09-01

    Acute pancreatitis (AP) usually causes acute lung injury, which is also known as acute pancreatitis associated lung injury (APALI). This study aimed to investigate whether captopril pretreatment was able to protect lung against APALI via inhibiting angiotensin II (Ang II) production and suppressing Rho/ROCK (Rho kinase) pathway in rats. Severe AP (SAP) was introduced to rats by bile-pancreatic duct retrograde injection of 5% sodium taurocholate. Rats were randomly divided into three groups. In the sham group, sham operation was performed; in the SAP group, SAP was introduced; in the pre-cpl + SAP group, rats were intragastrically injected with 5 mg/kg captopril 1 hour prior to SAP induction. Pathological examination of the lung and pancreas, evaluation of pulmonary vascular permeability by wet/dry ratio and Evans Blue staining, detection of serum amylase, Western blot assay for Ang II receptor type 1 (AT1), RhoA, ROCK (Rho kinase), and MLCK (myosin light chain kinase) were performed after the animals were sacrificed at 24 hours. After the surgery, characteristic findings of pancreatitis were observed, accompanied by lung injury. The serum amylase, Ang II, and lung expression of AT1, RhoA, ROCK, and MLCK increased dramatically in SAP rats. However, captopril pretreatment improved the histological changes, reduced the pathological score of the pancreas and lung, inhibited serum amylase and Ang II production, and decreased expression of AT1, RhoA, ROCK, and MLCK in the lung. These findings suggest that captopril pretreatment is able to protect the lung against APALI, which is, at least partially, related to the inhibition of Ang II production and the suppression of the Rho/ROCK pathway. PMID:27638402

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

    Science.gov (United States)

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

    2016-09-01

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

  9. Asiaticoside attenuates lipopolysaccharide-induced acute lung injury via down-regulation of NF-κB signaling pathway.

    Science.gov (United States)

    Qiu, Jiaming; Yu, Lijun; Zhang, Xingxing; Wu, Qianchao; Wang, Di; Wang, Xiuzhi; Xia, Cheng; Feng, Haihua

    2015-05-01

    Asiaticoside (AS), a triterpene glycoside isolated from Centella asiatica, has been shown to possess potent anti-inflammatory activity. However, the detailed molecular mechanisms of AS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in mice are scanty. The purpose of this study was to evaluate the effect of AS on LPS-induced mouse ALI via down-regulation of NF-κB signaling pathway. We investigated the efficacy of AS on cytokine levels induced by LPS in bronchoalveolar lavage fluid (BALF) and RAW 264.7 cells. The production of cytokine (TNF-α and IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). The lung wet-to-dry weight ratios were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. To further study the mechanism of AS protective effects on ALI, the activation of NF-κB p65 subunit and the degradation of IκBα were tested by western blot assay. We found that AS treatment at 15, 30 or 45mg/kg dose-dependently attenuated LPS-induced pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, our results suggested that AS suppressed inflammatory responses in LPS-induced ALI through inhibition of the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα, and might be a new preventive agent of ALI in the clinical setting.

  10. Disaturated-phosphatidylcholine and Surfactant protein-B turnover in human acute lung injury and in control patients

    Directory of Open Access Journals (Sweden)

    Rizzi Sabina

    2011-03-01

    Full Text Available Abstract Background Patients with Adult Respiratory Distress Syndrome (ARDS and Acute Lung Injury (ALI have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover. Objectives To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls. Methods 2H2O as precursor of disaturated-phosphatidylcholine-palmitate and 113C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the 2H and 13C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured. Results 1 Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2 In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p Conclusions 1 Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2 In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.

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

    Science.gov (United States)

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

    2014-07-15

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

  12. Level of complement activity predicts cardiac dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    2009-01-01

    BACKGROUND: The positive effect of reperfusion after ST-elevation myocardial infarction (STEMI) can be reduced by ischemic/reperfusion (I/R) injury.Mannose-binding-lectin (MBL) and soluble C5b-9 (membrane-attack-complex) are involved in complement-driven cell lysis and may play a role in human...... descending coronary artery who were successfully treated with pPCI. Cardiac dysfunction was defined as left ventricular ejection fraction LVEF or = 35%. After adjustment...

  13. Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia

    OpenAIRE

    Huh, Hee Jin; Park, Chan-Jeoung; Jang, Seongsoo; Seo, Eul-Ju; Chi, Hyun-Sook; Lee, Je-Hwan; Lee, Kyoo-Hyung; Seo, Jong Jin; Moon, Hyung Nam; Ghim, Thad

    2006-01-01

    The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of the...

  14. Risk markers of late high-degree atrioventricular block in patients with left ventricular dysfunction after an acute myocardial infarction: a CARISMA substudy

    DEFF Research Database (Denmark)

    Gang, Uffe Jakob Ortved; Jøns, Christian; Jørgensen, Rikke Mørch;

    2011-01-01

    AIMS: High-degree atrioventricular block (HAVB) after acute myocardial infarction (AMI) is associated with increased risk of mortality. Risk markers and predictors of HAVB occurring after AMI are largely unknown. The aim of this study was to assess the predictive value of risk markers derived from...... a series of non-invasive and invasive tests for the development of HAVB documented by an implantable loop recorder (ILR) in late convalescent phases of an AMI. METHODS AND RESULTS: The study included 292 patients with AMI and subsequent left ventricular dysfunction without prior HAVB or implanted pacemaker...... was documented in 28 (10%) patients during a median follow-up of 2.0 (0.4-2.0) years. Heart rate variability (HRV) measures and non-sustained ventricular tachycardia occurring at the week 6 Holter monitoring were highly predictive of HAVB. Power law slope

  15. Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes.

    Directory of Open Access Journals (Sweden)

    Adam A Anas

    Full Text Available BACKGROUND: Recognition of lipopolysaccharide (LPS is required for effective defense against invading gram-negative bacteria. Recently, in vitro studies revealed that CD14 is required for activation of the myeloid differentiation factor (MyD88-dependent Toll-like receptor (TLR4 signaling pathway by smooth (S-LPS, but not by rough (R-LPS. The present study investigated the role of CD14 in induction of lung inflammation in mice by these different LPS chemotypes. METHODOLOGY/RESULTS: Neutrophil accumulation and tumor necrosis factor (TNF release in bronchoalveolar lavage fluid were determined 6 hours after intranasal treatment of wild type (WT and CD14 knock-out (KO mice with different doses S-LPS or R-LPS. The contribution of CD14 to lung inflammation induced by S-LPS or R-LPS depended on the LPS dose. At low doses, S-LPS and R-LPS induced neutrophil influx in a CD14-dependent manner. Low dose S-LPS-induced cytokine release also depended on CD14. Strikingly, neutrophil influx and TNF release induced by high dose S-LPS or R-LPS was diminished in the presence of CD14. Intranasal administration of sCD14 to CD14 KO mice treated with S-LPS partially reversed the inflammatory response to the response observed in WT mice. CONCLUSIONS: In conclusion, CD14 modulates effects of both S-LPS and R-LPS within the lung in a similar way. Except for R-LPS-induced TNF release, S-LPS and R-LPS at low dose induced acute lung inflammation in a CD14-dependent manner, while the inflammatory response triggered by high dose S-LPS or R-LPS was diminished by CD14.

  16. Hyperbaric oxygen preconditioning protects the lung against acute pancreatitis induced injury via attenuating inflammation and oxidative stress in a nitric oxide dependent manner.

    Science.gov (United States)

    Yu, Qi-Hong; Zhang, Pei-Xi; Liu, Ying; Liu, Wenwu; Yin, Na

    2016-09-01

    This study aimed to investigate the protective effects of hyperbaric oxygen preconditioning (HBO-PC) on acute pancreatitis AP associated acute lung injury (ALI) and the potential mechanisms. Rats were randomly divided into sham group, AP group, HBO-PC + AP group and HBO-PC + L-NAME group. Rats in HBO-PC + AP group received HBO-PC once daily for 3 days, and AP was introduced 24 h after last HBO-PC. In HBO-PC + L-NAME group, L-NAME (40 mg/kg) was intraperitoneally injected before each HBO-PC. At 24 h after AP, the blood lipase and amylase activities were measured; the lung and pancreas were harvested for pathological examination; the bronchoalveolar lavage fluid was collected for the detection of lactate dehydrogenase (LDH) and proteins; inflammatory factors, superoxide dismutase (SOD) activity and malonaldehyde content were measured in the lung and blood; the Nrf2, SOD-1 and haem oxygenase-1 (HO-1) protein expression was measured in the lung. The lung nitric oxide (NO) and NO synthase activity increased significantly after HBO-PC. HBO-PC was able to reduce blood lipase and amylase activities, improve lung and pancreatic pathology, decrease LDH and proteins in BALF, inhibit the production of inflammatory factors, reduce malonaldehyde content and increase SOD activity in the lung and blood as well as increase protein expression of Nrf2, SOD-1 and HO-1 in the lung. However, L-NAME before HBO-PC significantly attenuated protective effects of HBO-PC. HBO-PC is able to protect the lung against AP induced injury by attenuating inflammation and oxidative stress in the lung via a NO dependent manner. PMID:27453338

  17. Lung

    International Nuclear Information System (INIS)

    At present no simple statement can be made relative to the role of radionuclidic lung studies in the pediatric population. It is safe to assume that they will be used with increasing frequency for research and clinical applications because of their sensitivity and ready applicability to the pediatric patient. Methods comparable to those used in adults can be used in children older than 4 years. In younger children, however, a single injection of 133Xe in solution provides an index of both regional perfusion and ventilation which is easier to accomplish. This method is particularly valuable in infants and neonates because it is rapid, requires no patient cooperation, results in a very low radiation dose, and can be repeated in serial studies. Radionuclidic studies of ventilation and perfusion can be performed in almost all children if the pediatrician and the nuclear medicine specialist have motivation and ingenuity. S

  18. 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

  19. Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell.

    Science.gov (United States)

    Inamdar, Ajinkya C; Inamdar, Arati A

    2013-10-01

    Lung disorders such as asthma, acute respiratory distress syndrome (ARDS), chronic obstructive lung disease (COPD), and interstitial lung disease (ILD) show a few common threads of pathogenic mechanisms: inflammation, aberrant immune activity, infection, and fibrosis. Currently no modes of effective treatment are available for ILD or emphysema. Being anti-inflammatory, immunomodulatory, and regenerative in nature, the administration of mesenchymal stem cells (MSCs) has shown the capacity to control immune dysfunction and inflammation in the lung. The intravenous infusion of MSCs, the common mode of delivery, is followed by their entrapment in lung vasculature before MSCs reach to other organ systems thus indicating the feasible and promising approach of MSCs therapy for lung diseases. In this review, we discuss the mechanistic basis for MSCs therapy for asthma, ARDS, COPD, and ILD. PMID:23992090

  20. Lung transplantation

    Science.gov (United States)

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  1. Dysfunctional Attitudes Scale Perfectionism: A Predictor and Partial Mediator of Acute Treatment Outcome among Clinically Depressed Adolescents

    Science.gov (United States)

    Jacobs, Rachel H.; Silva, Susan G.; Reinecke, Mark A.; Curry, John F.; Ginsburg, Golda S.; Kratochvil, Christopher J.; March, John S.

    2009-01-01

    The effect of perfectionism on acute treatment outcomes was explored in a randomized controlled trial of 439 clinically depressed adolescents (12-17 years of age) enrolled in the Treatment for Adolescents with Depression Study (TADS) who received cognitive behavior therapy (CBT), fluoxetine, a combination of CBT and FLX, or pill placebo. Measures…

  2. Differential prognostic importance of QRS duration in heart failure and acute myocardial infarction associated with left ventricular dysfunction

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Seibaek, Marie; Brendorp, Bente;

    2007-01-01

    . Dofetilide did not influence mortality in either trial. QRS duration was systematically measured at randomisation and was available in 2972 patients. RESULTS: Over a 10 year observation period 1037 (70%) patients in the MI study and 1324 (87%) in the HF study died. In the MI study, risk of death increased 6......% for each 10 ms increase in QRS duration (HR=1.06/10 ms increase in QRS (CI=1.04-1.09), pdeath...... in patients with left ventricular dysfunction who have suffered MI. In patients with HF QRS duration is not predictive of mortality....

  3. Acute pulmonary Oxygen toxicity in rats : findings and lung density changes in high resolution computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Dae Sik; Kang, Kil Hyen; Chung, Haingsup R.; Lee, Bung Wok; Mim, Young Ki; Lee, Tae Keun; Kim, Nam Hyeon; Jung, Seung Mun; Park, Man Soo [Kangnung Hospital, Asan Foundation, Kangnung (Korea, Republic of); Kim, Kun Sang [School of Medicine, Chung Ang University, Seoul (Korea, Republic of)

    2000-03-01

    To evaluate imaging findings and lung density changes after 95% oxygen inhalation in rat. A total of 18 rats were divided into three groups on the basis of inhalation time: group I (n=3D6) inhaled 95% oxygen for 24 hours, and group II (n=3D6) for 48 hours, group III (n=3D6) for 60 hours. A control group (n=3D6) inhaled room air (21% oxygen). Chest radiograph and high resolution computed tomography were performed, and pathologic and imaging findings were compared. Chest radiograph showed abnormality only in group III. High resolution CT, however, revealed abnormal findings in all three groups : diffuse ground glass opacity in groups I, II and III, additional focal patchy consolidation at the peripheral portion in group II, and diffuse consolidation in group III; Lung density was significantly higher in group I than in controls (p less than 0.05), while density in group II was not significantly different from that in group I (p greater than 0.05). In group III, density was significantly higher than in group II, The lung density changes seen in all groups showed a bilateral diffuse increased pattern. But, in group III, changes were more severe in the central, peripheral and posterior portion of the lower lung. Ground glass opacity and focal patchy consolidation seen on HRCT were found on pathologic examination to be due to alveolar cell hyperplasia and septal thickening. Consolidation was caused by alveolar edema and hemorrhage. Pathologic lesions were randomly distributed in both lungs. One HRCT images, rat exposed to hyperoxia showed ground glass opacity, patchy consolidation and diffuse consolidation. Depending on exposure time, the pathologic findings also indicated increased lung density and a bilateral, diffuse distribution pattern, as well as alveolar cell hyperplasia and septal thickening, alveolar edema and hemorrhage. HRCT may be more helpful than simple X-rays for the early detection of pulmonary oxygen toxicity. (author)

  4. Effect of acute ozone exposure on the proteinase-antiproteinase balance in the rat lung

    International Nuclear Information System (INIS)

    Lung disease may result from a persisting proteinase excess or a depletion of antiproteinase in pulmonary parenchyma. We investigated the in vivo effect of a 48-hr exposure to ozone at 0.5, 1.0, or 1.5 ppm on proteinase and antiproteinase activity of rat lungs. Elastase inhibitory capacities of serum, lung tissue, and airway washings were measured as indicators of antielastase activity. Trypsin inhibitory capacity was measured using an esterolytic procedure. Proteinase was measured as radioactive release from a 14C-globin substrate. The 48-hr exposures to O3 at levels up to 1 ppm produced concentration-dependent decreases of 35-80% of antiproteinase activities in serum and in lung tissue. However, exposure to 1.5 ppm O3 resulted in no decrease in antiproteinase activities. Acid proteinase activities (pH 4.2) were increased 65-120% by exposure to 1 or 1.5 ppm O3, which correlated with inflammatory cells noted histologically. At 1.5 ppm O3, pulmonary edema and hemorrhage were noted in histologic sections. These changes led to a flooding of the alveoli with up to 40 times normal protein levels and a greater than fivefold increase in airway antiproteinase. These data suggest that serum and soluble lung tissue antiproteinase activity decreased upon exposure to low levels of ozone. However, if O3 exposure is high enough to produce pulmonary hemorrhage, antiproteinase may increase following serum exudation. These changes may be important in the development of ozone-induced lung diseases, especially emphysema

  5. 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

  6. Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

    NARCIS (Netherlands)

    Wijsman, R.; Dankers, F.; Troost, E.G.; Hoffman, A.L.; Heijden, E. van der; Geus-Oei, L.F. de; Bussink, J.

    2015-01-01

    BACKGROUND AND PURPOSE: The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to d

  7. Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Suzuki, Yasuyuki; Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Sato, Yuichi [Health Park Clinic, Department of Imaging, Takasaki, Gunma (Japan)

    2015-04-01

    Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct. (orig.)

  8. Hyperglycemia, acute insulin resistance, and renal dysfunction in the early phase of ST-elevation myocardial infarction without previously known diabetes: impact on long-term prognosis.

    Science.gov (United States)

    Lazzeri, Chiara; Valente, Serafina; Chiostri, Marco; Attanà, Paola; Mattesini, Alessio; Nesti, Martina; Gensini, Gian Franco

    2014-11-01

    We evaluated the relationship between admission renal function (as assessed by estimated glomerular filtration rate (eGFR)), hyperglycemia, and acute insulin resistance, indicated by the homeostatic model assessment (HOMA) index, and their impact on long-term prognosis in 825 consecutive patients with ST-elevation myocardial infarction (STEMI) without previously known diabetes who underwent primary percutaneous coronary intervention (PCI). Admission eGFR showed a significant indirect correlation with admission glycemia (Spearman's ρ -0.23, P renal function and glucose values and acute insulin resistance in the early phase of STEMI was detectable, since a significant, indirect correlation between eGFR, insulin values, and glycemia was observed. Patients with renal dysfunction (eGFR renal function (eGFR ≥60 ml/min/1.73 m(2)). The prognostic role of glucose values for 1-year mortality was confined to patients with eGFR ≥60 ml/min/m(2), who represent the large part of our population and are thought to be at lower risk. In these patients, an independent relationship between 1-year mortality and glucose values was detectable not only for admission glycemia but also for glucose values measured at discharge.

  9. Effect on short- and long-term major adverse cardiac events of statin treatment in patients with acute myocardial infarction and renal dysfunction.

    Science.gov (United States)

    Lim, Sang Yup; Bae, Eun Hui; Choi, Joon Seok; Kim, Chang Seong; Park, Jeong Woo; Ma, Seong Kwon; Jeong, Myung Ho; Kim, Soo Wan

    2012-05-15

    The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduce major adverse cardiac events (MACE) and mortality in patients with acute coronary syndrome. We investigated the effectiveness of statin therapy in reducing MACE in patients with acute myocardial infarction (AMI) and renal dysfunction (RD). In the present retrospective study of 12,853 patients with AMI, the patients were categorized into 4 groups: group I, statin therapy and no RD (estimated glomerular filtration rate ≥60 ml/min/1.73 m(2)); group II, neither statin therapy nor RD; group III, statin therapy and RD; group IV, no statin therapy but RD. The primary end points were death and complications during the hospital course. The secondary end points were MACE during 1 year of follow-up after AMI. Significant differences in the composite MACE during 12 months of follow-up were observed among the 4 groups (group I, 11.7%; group II, 19.0%; group III, 26.7%; and group IV, 45.5%; p <0.001). In a Cox proportional hazards model, mortality at 12 months increased stepwise from group II to IV compared to group I. Moreover, MACE-free survival in the severe RD group (estimated glomerular filtration rate <30 mL/min/1.73 m(2)) was also greater in the statin-treated group. In conclusion, statin therapy reduced MACE at 1 year of follow-up in patients with AMI regardless of RD.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Li Lin

    2016-06-01

    Conclusion:These findings suggest that activated autophagy and apoptosis might play distinct roles at different stages of LPS-induced ALI. This information may enhance the understanding of lung pathophysiology at the cellular level during ALI and pulmonary infection, and thus help optimize the timing of innovating therapeutic approaches in future experiments with this model.

  12. [Renal infarction and acute arterial obstruction of the lower extremity encountered after surgery for primary lung cancer].

    Science.gov (United States)

    Tamaki, Masafumi; Miura, Kazumasa; Norimura, Shoko; Kenzaki, Koichirou; Yosizawa, Kiyoshi

    2013-02-01

    The patient was 68-year-old who underwent left upper lobectomy and lymph node dissection. On the 4th postoperative day, he developed vomiting and lumbar pain. On 5th postoperative day, he complained of pain, sensory paralysis and cold sensation of the right lower extremity. Computed tomography(CT)examination revealed left renal infarction and acute arterial obstruction of the right common iliac artery. Emergency thrombectomy of the right lower extremity was performed. Postoperatively, he received anticoagulant therapy and was able to leave the hospital on the 20th postoperative day. Attention should be paid to the infarction of abdominal organs when developing abdominal symptoms after lung cancer surgery in elderly patients.

  13. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

    Science.gov (United States)

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly

  14. Transfusion-related acute lung injury em pós-operatório de neurocirurgia: relato de caso Transfusion-related acute lung injury after following neurosurgery: case report

    Directory of Open Access Journals (Sweden)

    Salomón Soriano Ordinola Rojas

    2008-03-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O Transfusion-Related Acute Lung Injury (TRALI, é definido como um edema pulmonar não cardiogênico, relacionado à transfusão de sangue ou derivados, evoluindo com necessidade de ventilação mecânica na grande maioria dos casos. O objetivo deste estudo foi apresentar um caso de TRALI em pós-operatório imediato de neurocirurgia. RELATO DO CASO: Paciente do sexo masculino, 69 anos, sem comprometimento pulmonar prévio, foi submetido à ressecção cirúrgica de glioblastoma multiforme, apresentando complicações intra-operatórias (broncoespasmo e diminuição da saturação de oxigênio, após ter recebido plasma fresco congelado, sendo diagnosticado TRALI. O paciente foi mantido sedado, sob ventilação mecânica e monitorização hemodinâmica invasiva, com melhora progressiva do quadro, recebendo alta da unidade de terapia intensiva (UTI no 8º dia de pós-operatório. CONCLUSÕES: O TRALI deve ser investigado nos pacientes que recebem hemoderivados e apresentam alterações pulmonares.BACKGROUND AND OBJECTIVES: The Transfusion-Related Acute Lung Injury (TRALI, is defined as noncardiogenic pulmonary edema temporally related to transfusion therapy, evolving with ventilation necessity mechanics in the great majority of the cases. This objective of this study was to present case of TRALI in the immediate postoperative of neurosurgery. CASE REPORT: We describe the case of a patient who presented broncoespasm and decreased oxygen saturation after to have received fresh-frozen plasma in the neurosurgery, who presented TRALI. The patient was submitted a invasive hemodynamic monitoring, sedation and supplemental oxygen with mechanical ventilation, with gradual improvement, leaving the intensive care unit in the eight day of postoperative. CONCLUSIONS: The TRALI must be investigated in the patients who receive transfusion therapy and present lung injury.

  15. A specific phospholipase C activity regulates phosphatidylinositol levels in lung surfactant of patients with acute respiratory distress syndrome.

    Science.gov (United States)

    Spyridakis, Spyros; Leondaritis, George; Nakos, George; Lekka, Marilena E; Galanopoulou, Dia

    2010-03-01

    Lung surfactant (LS) is a lipid-rich material lining the inside of the lungs. It reduces surface tension at the liquid/air interface and thus, it confers protection of the alveoli from collapsing. The surface-active component of LS is dipalmitoyl-phosphatidylcholine, while anionic phospholipids such as phosphatidylinositol (PtdIns) and primarily phosphatidylglycerol are involved in the stabilization of the LS monolayer. The exact role of PtdIns in this system is not well-understood; however, PtdIns levels change dramatically during the acute respiratory distress syndrome (ARDS) evolution. In this report we present evidence of a phosphoinositide-specific phospholipase C (PI-PLC) activity in bronchoalveolar lavage (BAL) fluid, which may regulate PtdIns levels. Characterization of this extracellular activity showed specificity for PtdIns and phosphatidylinositol 4,5-bisphosphate, sharing the typical substrate concentration-, pH-, and calcium-dependencies with mammalian PI-PLCs. Fractionation of BAL fluid showed that PI-PLC did not co-fractionate with large surfactant aggregates, but it was found mainly in the soluble fraction. Importantly, analysis of BAL samples from control subjects and from patients with ARDS showed that the PI-PLC specific activity was decreased by 4-fold in ARDS samples concurrently with the increase in BAL PtdIns levels. Thus, we have identified for the first time an extracellular PI-PLC enzyme activity that may be acutely involved in the regulation of PtdIns levels in LS. PMID:19491339

  16. High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

    Directory of Open Access Journals (Sweden)

    Kuiper Jan

    2011-12-01

    Full Text Available Abstract Background To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI and resultant systemic inflammatory responses. Methods Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV with either a low tidal volume (Vt of 6 mL/kg and 5 cm H2O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis. Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D weight ratios, histological lung injury and plasma mediator concentrations were measured. Results Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and