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Sample records for resolve experimental lung

  1. CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury

    PubMed Central

    D’Alessio, Franco R.; Tsushima, Kenji; Aggarwal, Neil R.; West, Erin E.; Willett, Matthew H.; Britos, Martin F.; Pipeling, Matthew R.; Brower, Roy G.; Tuder, Rubin M.; McDyer, John F.; King, Landon S.

    2009-01-01

    Acute lung injury (ALI) is characterized by rapid alveolar injury, inflammation, cytokine induction, and neutrophil accumulation. Although early events in the pathogenesis of ALI have been defined, the mechanisms underlying resolution are unknown. As a model of ALI, we administered intratracheal (i.t.) LPS to mice and observed peak lung injury 4 days after the challenge, with resolution by day 10. Numbers of alveolar lymphocytes increased as injury resolved. To examine the role of lymphocytes in this response, lymphocyte-deficient Rag-1–/– and C57BL/6 WT mice were exposed to i.t. LPS. The extent of injury was similar between the groups of mice through day 4, but recovery was markedly impaired in the Rag-1–/– mice. Adoptive transfer studies revealed that infusion of CD4+CD25+Foxp3+ Tregs as late as 24 hours after i.t. LPS normalized resolution in Rag-1–/– mice. Similarly, Treg depletion in WT mice delayed recovery. Treg transfer into i.t. LPS–exposed Rag-1–/– mice also corrected the elevated levels of alveolar proinflammatory cytokines and increased the diminished levels of alveolar TGF-β and neutrophil apoptosis. Mechanistically, Treg-mediated resolution of lung injury was abrogated by TGF-β inhibition. Moreover, BAL of patients with ALI revealed dynamic changes in CD3+CD4+CD25hiCD127loFoxp3+ cells. These results indicate that Tregs modify innate immune responses during resolution of lung injury and suggest potential targets for treating ALI, for which there are no specific therapies currently available. PMID:19770521

  2. Neurological outcome after experimental lung injury.

    PubMed

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

    2011-12-15

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

  3. Noninvasive Imaging of Experimental Lung Fibrosis

    PubMed Central

    Chen, Huaping; Ambalavanan, Namasivayam; Liu, Gang; Antony, Veena B.; Ding, Qiang; Nath, Hrudaya; Eary, Janet F.; Thannickal, Victor J.

    2015-01-01

    Small animal models of lung fibrosis are essential for unraveling the molecular mechanisms underlying human fibrotic lung diseases; additionally, they are useful for preclinical testing of candidate antifibrotic agents. The current end-point measures of experimental lung fibrosis involve labor-intensive histological and biochemical analyses. These measures fail to account for dynamic changes in the disease process in individual animals and are limited by the need for large numbers of animals for longitudinal studies. The emergence of noninvasive imaging technologies provides exciting opportunities to image lung fibrosis in live animals as often as needed and to longitudinally track the efficacy of novel antifibrotic compounds. Data obtained by noninvasive imaging provide complementary information to histological and biochemical measurements. In addition, the use of noninvasive imaging in animal studies reduces animal usage, thus satisfying animal welfare concerns. In this article, we review these new imaging modalities with the potential for evaluation of lung fibrosis in small animal models. Such techniques include micro-computed tomography (micro-CT), magnetic resonance imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and multimodal imaging systems including PET/CT and SPECT/CT. It is anticipated that noninvasive imaging will be increasingly used in animal models of fibrosis to gain insights into disease pathogenesis and as preclinical tools to assess drug efficacy. PMID:25679265

  4. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model.

    PubMed

    Medeiros, Israel L; Pêgo-Fernandes, Paulo M; Mariani, Alessandro W; Fernandes, Flávio G; Unterpertinger, Fernando V; Canzian, Mauro; Jatene, Fabio B

    2012-09-01

    Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98). The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035). The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816). The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87). The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0), and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71). The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

  5. Clinical and experimental pathology of lung cancer

    SciTech Connect

    McVie, J.G.; Bakker, W.; Wagenaar, S.C.; Carney, D.

    1986-01-01

    This book contains 17 selections. Some of the titles are: Flow cytometric DNA analysis in the study of small cell carcinoma of the lung; Mechanisms of oncogenesis; Adhesion mechanisms in liver metastasis; Current concepts in the therapy of small cell lung cancer; Application of monoclonal antibodies in imaging and therapy; and Clinical applications of the biologic properties of small cell lung cancer.

  6. Stable isotope resolved metabolomics of lung cancer in a SCID mouse model.

    PubMed

    Fan, Teresa W-M; Lane, Andrew N; Higashi, Richard M; Yan, Jun

    2011-06-01

    We have determined the time course of [U-(13)C]-glucose utilization and transformations in SCID mice via bolus injection of the tracer in the tail vein. Incorporation of (13)C into metabolites extracted from mouse blood plasma and several tissues (lung, heart, brain, liver, kidney, and skeletal muscle) were profiled by NMR and GC-MS, which helped ascertain optimal sampling times for different target tissues. We found that the time for overall optimal (13)C incorporation into tissue was 15-20 min but with substantial differences in (13)C labeling patterns of various organs that reflected their specific metabolism. Using this stable isotope resolved metabolomics (SIRM) approach, we have compared the (13)C metabolite profile of the lungs in the same mouse with or without an orthotopic lung tumor xenograft established from human PC14PE6 lung adenocarcinoma cells. The (13)C metabolite profile shows considerable differences in [U-(13)C]-glucose transformations between the two lung tissues, demonstrating the feasibility of applying SIRM to investigate metabolic networks of human cancer xenograft in the mouse model.

  7. Energy-resolved computed tomography: first experimental results.

    PubMed

    Shikhaliev, Polad M

    2008-10-21

    First experimental results with energy-resolved computed tomography (CT) are reported. The contrast-to-noise ratio (CNR) in CT has been improved with x-ray energy weighting for the first time. Further, x-ray energy weighting improved the CNR in material decomposition CT when applied to CT projections prior to dual-energy subtraction. The existing CT systems use an energy (charge) integrating x-ray detector that provides a signal proportional to the energy of the x-ray photon. Thus, the x-ray photons with lower energies are scored less than those with higher energies. This underestimates contribution of lower energy photons that would provide higher contrast. The highest CNR can be achieved if the x-ray photons are scored by a factor that would increase as the x-ray energy decreases. This could be performed by detecting each x-ray photon separately and measuring its energy. The energy selective CT data could then be saved, and any weighting factor could be applied digitally to a detected x-ray photon. The CT system includes a photon counting detector with linear arrays of pixels made from cadmium zinc telluride (CZT) semiconductor. A cylindrical phantom with 10.2 cm diameter made from tissue-equivalent material was used for CT imaging. The phantom included contrast elements representing calcifications, iodine, adipose and glandular tissue. The x-ray tube voltage was 120 kVp. The energy selective CT data were acquired, and used to generate energy-weighted and material-selective CT images. The energy-weighted and material decomposition CT images were generated using a single CT scan at a fixed x-ray tube voltage. For material decomposition the x-ray spectrum was digitally spilt into low- and high-energy parts and dual-energy subtraction was applied. The x-ray energy weighting resulted in CNR improvement of calcifications and iodine by a factor of 1.40 and 1.63, respectively, as compared to conventional charge integrating CT. The x-ray energy weighting was also applied

  8. Energy-resolved computed tomography: first experimental results

    NASA Astrophysics Data System (ADS)

    Shikhaliev, Polad M.

    2008-10-01

    First experimental results with energy-resolved computed tomography (CT) are reported. The contrast-to-noise ratio (CNR) in CT has been improved with x-ray energy weighting for the first time. Further, x-ray energy weighting improved the CNR in material decomposition CT when applied to CT projections prior to dual-energy subtraction. The existing CT systems use an energy (charge) integrating x-ray detector that provides a signal proportional to the energy of the x-ray photon. Thus, the x-ray photons with lower energies are scored less than those with higher energies. This underestimates contribution of lower energy photons that would provide higher contrast. The highest CNR can be achieved if the x-ray photons are scored by a factor that would increase as the x-ray energy decreases. This could be performed by detecting each x-ray photon separately and measuring its energy. The energy selective CT data could then be saved, and any weighting factor could be applied digitally to a detected x-ray photon. The CT system includes a photon counting detector with linear arrays of pixels made from cadmium zinc telluride (CZT) semiconductor. A cylindrical phantom with 10.2 cm diameter made from tissue-equivalent material was used for CT imaging. The phantom included contrast elements representing calcifications, iodine, adipose and glandular tissue. The x-ray tube voltage was 120 kVp. The energy selective CT data were acquired, and used to generate energy-weighted and material-selective CT images. The energy-weighted and material decomposition CT images were generated using a single CT scan at a fixed x-ray tube voltage. For material decomposition the x-ray spectrum was digitally spilt into low- and high-energy parts and dual-energy subtraction was applied. The x-ray energy weighting resulted in CNR improvement of calcifications and iodine by a factor of 1.40 and 1.63, respectively, as compared to conventional charge integrating CT. The x-ray energy weighting was also applied

  9. Lung release of HIPDM: A new index of lung dysfunction for clinical and experimental studies

    SciTech Connect

    Pistolesi, M.; Miniati, M.; Ghelarducci, L.; Mazzuca, N.; Giuntini, C.; Taccini, E.; Renzoni, G.; Pellegrini, N.; Gilardi, M.C.; Gerundini, P.

    1985-05-01

    Lung uptake, metabolism and release of amines has been experimentally documented. The authors studied in rabbit and man the lung kinetics of radioiodinated N-N-N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1, 3-propanediamine (HIPDM). In rabbits, after i.v. injection, 95% of HIPDM is kept within the lungs and is then released with a mean time (t-bar) of several hours as assessed both in vivo, by gamma camera external counting (n=5; t-bar=7.0 hrs), and in vitro by measuring activity in lung homogenates at various times after injection (n=56; t-bar=7.6 hrs). In 10 healthy non smoking subjects t-bar was 6.4 +- 1 hrs, whereas it was 12.1 +- 2 hrs in 10 asymptomatic smokers with normal pulmonary function tests. Preliminary clinical studies showed that HIPDM lung release is delayed in non smoking patients with primary pulmonary hypertension (n=4; t-bar=11.5 +- 2 hrs) and to a greater extent in adult respiratory distress syndrome (n=4; t-bar=25.8 +- 5hrs), whereas it was not significantly affected in cardiogenic pulmonary edema (n=4; t-bar=8.8 +- 2 hrs). Hence, both smoke exposure and injury to the lung microcirculation may impair HIPDM lung kinetics. HIPDM external counting may therefore provide a new index of lung dysfunction in man. Rabbit can be used as a model to evaluate HIPDM lung kinetics in experimentally induced lung injury.

  10. Inflammation-induced preterm lung maturation: lessons from animal experimentation.

    PubMed

    Moss, Timothy J M; Westover, Alana J

    2017-06-01

    Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

  11. Experimental Time Resolved Electron Beam Temperature Measurements Using Bremsstrahlung Diagnostics

    SciTech Connect

    Menge, P.R.; Maenchen, J.E.; Mazarakis, M.G.; Rosenthal, S.E.

    1999-06-25

    Electron beam temperature, {beta}{perpendicular} (= v{perpendicular}/v), is important to control for the development of high dose flash radiographic bremsstrahlung sources. At high voltage (> 5 MV) increasing electron beam temperature has a serious deleterious effect on dose production. The average and time resolved behavior of beam temperature was measured during radiographic experiments on the HERMES III accelerator (10 MV, 50 kA, 70 ns). A linear array of thermoluminescent dosimeters (TLDs) were used to estimate the time integrated average of beam temperature. On and off-axis photoconducting diamond (PCD) detectors were used to measure the time resolved bremsstrahlung dose rate, which is dependent on beam energy and temperature. The beam temperature can be determined by correlating PCD response with accelerator voltage and current and also by analyzing the ratio of PCD amplitudes on and off axis. This ratio is insensitive to voltage and current and thus, is more reliable than utilizing absolute dose rate. The data is unfolded using comparisons with Monte Carlo simulations to obtain absolute beam temperatures. The data taken on HERMES III show abrupt increases in {beta}{perpendicular} midway through the pulse indicating rapid onset of beam instability.

  12. Bosutinib Therapy Ameliorates Lung Inflammation and Fibrosis in Experimental Silicosis.

    PubMed

    Carneiro, Priscila J; Clevelario, Amanda L; Padilha, Gisele A; Silva, Johnatas D; Kitoko, Jamil Z; Olsen, Priscilla C; Capelozzi, Vera L; Rocco, Patricia R M; Cruz, Fernanda F

    2017-01-01

    Silicosis is an occupational lung disease for which no effective therapy exists. We hypothesized that bosutinib, a tyrosine kinase inhibitor, might ameliorate inflammatory responses, attenuate pulmonary fibrosis, and thus improve lung function in experimental silicosis. For this purpose, we investigated the potential efficacy of bosutinib in the treatment of experimental silicosis induced in C57BL/6 mice by intratracheal administration of silica particles. After 15 days, once disease was established, animals were randomly assigned to receive DMSO or bosutinib (1 mg/kg/dose in 0.1 mL 1% DMSO) by oral gavage, twice daily for 14 days. On day 30, lung mechanics and morphometry, total and differential cell count in alveolar septa and granuloma, levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, transforming growth factor (TGF)-β, and vascular endothelial growth factor in lung homogenate, M1 and M2 macrophages, total leukocytes, and T cells in BALF, lymph nodes, and thymus, and collagen fiber content in alveolar septa and granuloma were analyzed. In a separate in vitro experiment, RAW264.7 macrophages were exposed to silica particles in the presence or absence of bosutinib. After 24 h, gene expressions of arginase-1, IL-10, IL-12, inducible nitric oxide synthase (iNOS), metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, and caspase-3 were evaluated. In vivo, in silicotic animals, bosutinib, compared to DMSO, decreased: (1) fraction area of collapsed alveoli, (2) size and number of granulomas, and mononuclear cell granuloma infiltration; (3) IL-1β, TNF-α, IFN-γ, and TGF-β levels in lung homogenates, (4) collagen fiber content in lung parenchyma, and (5) viscoelastic pressure and static lung elastance. Bosutinib also reduced M1 cell counts while increasing M2 macrophage population in both lung parenchyma and granulomas. Total leukocyte, regulatory T, CD4(+), and CD8(+) cell counts in the lung

  13. Bosutinib Therapy Ameliorates Lung Inflammation and Fibrosis in Experimental Silicosis

    PubMed Central

    Carneiro, Priscila J.; Clevelario, Amanda L.; Padilha, Gisele A.; Silva, Johnatas D.; Kitoko, Jamil Z.; Olsen, Priscilla C.; Capelozzi, Vera L.; Rocco, Patricia R. M.; Cruz, Fernanda F.

    2017-01-01

    Silicosis is an occupational lung disease for which no effective therapy exists. We hypothesized that bosutinib, a tyrosine kinase inhibitor, might ameliorate inflammatory responses, attenuate pulmonary fibrosis, and thus improve lung function in experimental silicosis. For this purpose, we investigated the potential efficacy of bosutinib in the treatment of experimental silicosis induced in C57BL/6 mice by intratracheal administration of silica particles. After 15 days, once disease was established, animals were randomly assigned to receive DMSO or bosutinib (1 mg/kg/dose in 0.1 mL 1% DMSO) by oral gavage, twice daily for 14 days. On day 30, lung mechanics and morphometry, total and differential cell count in alveolar septa and granuloma, levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, transforming growth factor (TGF)-β, and vascular endothelial growth factor in lung homogenate, M1 and M2 macrophages, total leukocytes, and T cells in BALF, lymph nodes, and thymus, and collagen fiber content in alveolar septa and granuloma were analyzed. In a separate in vitro experiment, RAW264.7 macrophages were exposed to silica particles in the presence or absence of bosutinib. After 24 h, gene expressions of arginase-1, IL-10, IL-12, inducible nitric oxide synthase (iNOS), metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, and caspase-3 were evaluated. In vivo, in silicotic animals, bosutinib, compared to DMSO, decreased: (1) fraction area of collapsed alveoli, (2) size and number of granulomas, and mononuclear cell granuloma infiltration; (3) IL-1β, TNF-α, IFN-γ, and TGF-β levels in lung homogenates, (4) collagen fiber content in lung parenchyma, and (5) viscoelastic pressure and static lung elastance. Bosutinib also reduced M1 cell counts while increasing M2 macrophage population in both lung parenchyma and granulomas. Total leukocyte, regulatory T, CD4+, and CD8+ cell counts in the lung-draining lymph

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

    PubMed Central

    Gilliss, Brian M.; Looney, Mark R.

    2010-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. PMID:21134622

  15. Time-resolved autofluorescence measurements for the differentiation of lung tissue states

    NASA Astrophysics Data System (ADS)

    Pfeifer, Lutz; Schmalzigaug, K.; Paul, Rene; Lichey, J.; Kemnitz, Klaus; Fink, Frank

    1995-12-01

    The fluorescence properties of fluorophores relevant in tissue metabolism (NADH, flavines, etc.) are characteristic of the clinical states of tissues. Especially the differentiation of healthy, cancerous, and necrotic tissue states is of large interest in lung-tumor diagnostics, e.g. to ensure that biopsies are taken from non-necrotic areas. In contrast to the common fluorescence detection our approach provides both a combination of spectral and time information from autofluorescence and the simultaneous detection of two fluorophores in order to improve differentiation between various tissues. The basis of analysis of autofluorescence is knowledge of the photophysical parameters of the fluorophores. Aqueous solutions of NADH, flavines and their mixtures have been investigated using the method of time-correlated single photon counting. The fluorescence was recorded with a new 'delay-line' microchannel-plate photomultiplier tube, that enables time- and wavelength-resolved measurements simultaneously. Nicotine-adenine-dinucleotide (NADH) and flavine-adenin-dinucleotide (FAD) display their characteristic temporal behavior (NADH: (tau) 1 equals 250 ps, (tau) 2 equals 660 ps; FAD: (tau) 1 equals 160 ps, (tau) 2 equals 2.25 ns, (tau) 3 equals 4.6 ns) in aqueous solution. In a mixture of NADH and FAD both components could be isolated by using global analytical methods. Time-gated fluorescence measurements on lung-tissue samples of 12 patients immediately after surgical resection have been performed with a fiber- based fluorescence detector. It could be demonstrated that NADH measurements are suitable for differentiating tumorous and necrotic tissue while flavine measurements are suitable for differentiating healthy and non-healthy tissue types. Applications of optical fibers facilitate simple combinations of the detection method with common surgical instruments (e.g. biopsy needles).

  16. Stable Isotope Resolved Metabolomics Analysis of Ribonucleotide and RNA Metabolism in Human Lung Cancer Cells.

    PubMed

    Fan, Teresa W-M; Tan, Jinlian; McKinney, Martin M; Lane, Andrew N

    2012-06-01

    We have developed a simple NMR-based method to determine the turnover of nucleotides and incorporation into RNA by stable isotope resolved metabolomics (SIRM) in A549 lung cancer cells. This method requires no chemical degradation of the nucleotides or chromatography. During cell growth, the free ribonucleotide pool is rapidly replaced by de novo synthesized nucleotides. Using [U-(13)C]-glucose and [U-(13)C,(15)N]-glutamine as tracers, we showed that virtually all of the carbons in the nucleotide riboses were derived from glucose, whereas glutamine was preferentially utilized over glucose for pyrimidine ring biosynthesis, via the synthesis of Asp through the Krebs cycle. Incorporation of the glutamine amido nitrogen into the N3 and N9 positions of the purine rings was also demonstrated by proton-detected (15)N NMR. The incorporation of (13)C from glucose into total RNA was measured and shown to be a major sink for the nucleotides during cell proliferation. This method was applied to determine the metabolic action of an anti-cancer selenium agent (methylseleninic acid or MSA) on A549 cells. We found that MSA inhibited nucleotide turnover and incorporation into RNA, implicating an important role of nucleotide metabolism in the toxic action of MSA on cancer cells.

  17. Experimental lung mycotoxicosis in mice induced by Stachybotrys atra

    PubMed Central

    Nikulin, Marjo; Reijula, Kari; Jarvis, Bruce B.; Hintikka, Eeva-Liisa

    1996-01-01

    Stachybotrys atra is often isolated from building materials in houses with moisture problems. Spores of S. atra can contain mycotoxins which may lead to various symptoms in exposed residents in damp houses. The pathogenesis of S. atra-induced lung diseases has not been elucidated. The purpose of the present study was to investigate lung mycotoxicosis experimentally in mice after an intranasal exposure to spores of S. atra-fungus. One group of mice received one intranasal injection of spores of a toxic strain of S. atra (1 × 106 spores) and the other group spores of a less toxic strain. Spores of both strains contained spirolactones and spirolactams while the highly toxic strain contained also trichothecene mycotoxins, satratoxins. The spores containing satratoxins caused severe intra-alveolar, bronchiolar and interstitial inflammation with haemorrhagic exudative processes in the alveolar and bronchiolar lumen. A significant difference was observed in the severity of the lung damage caused by the two strains of S. atra. The spores without satratoxins induced a milder inflammation, so that the toxic compounds of S. atra-spores are most likely responsible for the severity of the lung injury. PMID:8977373

  18. Effects of sevoflurane on ventilator induced lung injury in a healthy lung experimental model.

    PubMed

    Romero, A; Moreno, A; García, J; Sánchez, C; Santos, M; García, J

    2016-01-01

    Ventilator-induced lung injury (VILI) causes a systemic inflammatory response in tissues, with an increase in IL-1, IL-6 and TNF-α in blood and tissues. Cytoprotective effects of sevoflurane in different experimental models are well known, and this protective effect can also be observed in VILI. The objective of this study was to assess the effects of sevoflurane in VILI. A prospective, randomized, controlled study was designed. Twenty female rats were studied. The animals were mechanically ventilated, without sevoflurane in the control group and sevoflurane 3% in the treated group (SEV group). VILI was induced applying a maximal inspiratory pressure of 35 cmH2O for 20 min without any positive end-expiratory pressure for 20 min (INJURY time). The animals were then ventilated 30 min with a maximal inspiratory pressure of 12 cmH2O and 3 cmH2O positive end-expiratory pressure (time 30 min POST-INJURY), at which time the animals were euthanized and pathological and biomarkers studies were performed. Heart rate, invasive blood pressure, pH, PaO2, and PaCO2 were recorded. The lung wet-to-dry weight ratio was used as an index of lung edema. No differences were found in the blood gas analysis parameters or heart rate between the 2 groups. Blood pressure was statistically higher in the control group, but still within the normal clinical range. The percentage of pulmonary edema and concentrations of TNF-α and IL-6 in lung tissue in the SEV group were lower than in the control group. Sevoflurane attenuates VILI in a previous healthy lung in an experimental subclinical model in rats. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Resolving DOI Based URNs Using Squid: An Experimental System at UKOLN.

    ERIC Educational Resources Information Center

    Powell, Andy

    1998-01-01

    Describes UKOLN's (United Kingdom Office for Library and Information Networking--a national center for support in network information management in the library/information communities) experimental system that allows digital object identifiers (DOIs) encoded as uniform resource names (URNs) to be resolved on behalf of Web browsers by Squid, a…

  20. Experimental results on time-resolved reflectance diffuse optical tomography with fast-gated SPADs

    NASA Astrophysics Data System (ADS)

    Puszka, Agathe; Di Sieno, Laura; Dalla Mora, Alberto; Pifferi, Antonio; Contini, Davide; Boso, Gianluca; Tosi, Alberto; Planat-Chrétien, Anne; Hervé, Lionel; Koenig, Anne; Dinten, Jean-Marc

    2013-06-01

    We present experimental results of time-resolved reflectance diffuse optical tomography performed with fast-gated single-photon avalanche diodes (SPADs) and show an increased imaged depth range for a given acquisition time compared to the non gated mode.

  1. Resolving DOI Based URNs Using Squid: An Experimental System at UKOLN.

    ERIC Educational Resources Information Center

    Powell, Andy

    1998-01-01

    Describes UKOLN's (United Kingdom Office for Library and Information Networking--a national center for support in network information management in the library/information communities) experimental system that allows digital object identifiers (DOIs) encoded as uniform resource names (URNs) to be resolved on behalf of Web browsers by Squid, a…

  2. Development of the Experimental System for Time- and Angle-resolved Photoemission Spectroscopy

    SciTech Connect

    Takahashi, Kazutoshi; Azuma, Junpei; Tokudomi, Shinji; Kamada, Masao

    2007-01-19

    Experimental system for the time- and angle-resolved photoemission spectroscopy have been constructed at BL13 in SAGA Light Source, in order to study the electronic non-equilibrium in the surface layer of laser-excited materials The experimental system is very useful for photoemission spectroscopy in the wide temporal and angular ranges. The time- and angle-resolved photoemission spectra can be obtained with using the gate electronics for the MCP detector of the photoemission spectrometer. The gated MCP detector is synchronized with the laser pulse from Ti:sapphire regenerative amplifier with the repetition frequency of 10 to 300 kHz. The time-window of the gated MCP detector can be changed between 10 nano- and 160 micro-second. The time-resolved measurement in pico-second region can be performed with using the pump-probe technique which uses fundamental, second and third harmonics from the Ti:sapphire laser as the excitation source. Using these systems, we can perform the time- and angle-resolved photoemission study for various photo-excited phenomena and surface dynamics.

  3. Platelet glycoprotein Ibα supports experimental lung metastasis

    PubMed Central

    Jain, Shashank; Zuka, Masahiko; Liu, Jungling; Russell, Susan; Dent, Judith; Guerrero, José A.; Forsyth, Jane; Maruszak, Brigid; Gartner, T. Kent; Felding-Habermann, Brunhilde; Ware, Jerry

    2007-01-01

    The platelet paradigm in hemostasis and thrombosis involves an initiation step that depends on platelet membrane receptors binding to ligands on a damaged or inflamed vascular surface. Once bound to the surface, platelets provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin-rich network produced by coagulation factors. The platelet-specific receptor glycoprotein (GP) Ib-IX, is critical in this process and initiates the formation of a platelet-rich thrombus by tethering the platelet to a thrombogenic surface. A role for platelets beyond the hemostasis/thrombosis paradigm is emerging with significant platelet contributions in both tumorigenesis and inflammation. We have established congenic (N10) mouse colonies (C57BL/6J) with dysfunctional GP Ib-IX receptors in our laboratory that allow us an opportunity to examine the relevance of platelet GP Ib-IX in syngeneic mouse models of experimental metastasis. Our results demonstrate platelet GP Ib-IX contributes to experimental metastasis because a functional absence of GP Ib-IX correlates with a 15-fold reduction in the number of lung metastatic foci using B16F10.1 melanoma cells. The results demonstrate that the extracellular domain of the α-subunit of GP Ib is the structurally relevant component of the GP Ib-IX complex contributing to metastasis. Our results support the hypothesis that platelet GP Ib-IX functions that support normal hemostasis or pathologic thrombosis also contribute to tumor malignancy. PMID:17494758

  4. Experimental and Computational Models for Simulating Sound Propagation Within the Lungs

    PubMed Central

    Acikgoz, S.; Ozer, M. B.; Mansy, H. A.; Sandler, R. H.

    2008-01-01

    An acoustic boundary element model is used to simulate sound propagation in the lung parenchyma and surrounding chest wall. It is validated theoretically and numerically and then compared with experimental studies on lung-chest phantom models that simulate the lung pathology of pneumothorax. Studies quantify the effect of the simulated lung pathology on the resulting acoustic field measured at the phantom chest surface. This work is relevant to the development of advanced auscultatory techniques for lung, vascular, and cardiac sounds within the torso that utilize multiple noninvasive sensors to create acoustic images of the sound generation and transmission to identify certain pathologies. PMID:18568101

  5. Lung imaging fluorescence endoscope: development and experimental prototype

    NASA Astrophysics Data System (ADS)

    Palcic, Branko; Lam, Stephen; MacAulay, Calum E.; Hung, Jaclyn; Jaggi, Bruno; Radjinia, Massud; Pon, Alfred; Profio, A. E.

    1991-06-01

    A lung imaging fluorescence endoscope has been developed which can be used for detection and localization of early lung cancer. We exploited tissue autofluorescence alone or in combination with fluorescent tumor localizing drugs to create pseudo images which can clearly delineate the diseased sites from the surrounding normal tissues. With this technique it is possible to detect early lung cancer as well as pre-cancerous lesions of one to two millimeters in diameter and only a few cell layers thick.

  6. Application of Monte Carlo technique to time-resolved transillumination: a comparison with experimental data

    NASA Astrophysics Data System (ADS)

    Scampoli, Paola; Curto, C. A.; Guida, Giovanni; Roberti, Giuseppe

    1998-01-01

    The growing number of laser applications in medicine and biology has determined a renewed interest on the study of the light transport in turbid media such as biological tissues. One of the most powerful methods used to describe this kind of process is given by the Monte Carlo techniques. We have developed a FORTRAN90 code, running on an Alpha Vax AXP DEC 2100 to simulate the transport of a photon beam with a Gaussian temporal and spatial profile through a multilayered sample. The code provides the sample transmittance and reflectance (both time and space resolved) that can be compared to the experimental data. Monte Carlo calculations have been performed to simulate time-resolved transillumination through water latex and intralipid water solutions with optical properties similar to those of biological tissues. The comparison of Monte Carlo results with experimental data and with analytical solutions to diffusion equation shows a good agreement, suggesting that Monte Carlo techniques are indeed a powerful tool for predictions on light transport in turbid media.

  7. Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis.

    PubMed

    Eickmeier, Olaf; Fussbroich, Daniela; Mueller, Klaus; Serve, Friederike; Smaczny, Christina; Zielen, Stefan; Schubert, Ralf

    2017-01-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05). SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients

  8. Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis

    PubMed Central

    Fussbroich, Daniela; Mueller, Klaus; Serve, Friederike; Smaczny, Christina; Zielen, Stefan; Schubert, Ralf

    2017-01-01

    Background Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. Methods In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. Results DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05). Conclusions SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was

  9. Serum copper concentration as an index of experimental lung injury

    SciTech Connect

    Ward, W.F.; Molteni, A.; Ts'ao, C.; Ischiropoulos, H. )

    1989-01-01

    Serum copper (Cu) concentration was evaluated as an index of lung injury in two rat models of pneumotoxicity: hemithoracic irradiation and monocrotaline ingestion. In both models there was a dose- and time-dependent increase in serum Cu concentration. This hypercupremia paralleled the development of pulmonary endothelial dysfunction (decreased lung plasminogen activator activity and increased prostacyclin production) and pulmonary fibrosis (hydroxyproline accumulation). In the radiation model, lung injury and hypercupremia persisted for at least 6 months, and were spared similarly when the total dose was delivered in multiple daily fractions as compared to single doses. In irradiated rats, the elevated serum Cu concentration was accompanied by increases in plasma ceruloplasmin, lung Cu concentration, and lung Cu/Zn superoxide dismutase (SOD) activity. In monocrotaline-treated rats, lung damage and hypercupremia also were accompanied by a reduction in liver Cu concentration, and by a direct correlation between the concentrations of Cu and SGOT in the serum. In both models, some but not all modifiers of lung damage (penicillamine, angiotensin converting enzyme inhibitors, pentoxifylline) also partially prevented the insult-induced hypercupremia. In contrast, serum iron concentration was largely independent of treatment in all experiments. These data suggest that elevated serum copper concentration is an accurate and minimally invasive index of lung injury in irradiated and monocrotaline-treated rats.

  10. Corilagin Attenuates Aerosol Bleomycin-Induced Experimental Lung Injury

    PubMed Central

    Wang, Zheng; Guo, Qiong-Ya; Zhang, Xiao-Ju; Li, Xiao; Li, Wen-Ting; Ma, Xi-Tao; Ma, Li-Jun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressing lethal disease with few clinically effective therapies. Corilagin is a tannin derivative which shows anti-inflammatory and antifibrotics properties and is potentiated in treating IPF. Here, we investigated the effect of corilagin on lung injury following bleomycin exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin-induced lung fibrosis as assessed by H&E; Masson’s trichrome staining and lung hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic lung cells and prevented lung epithelial cells from membrane breakdown, effluence of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure induced expression of MDA, IKKα, phosphorylated IKKα (p-IKKα), NF-κB P65, TNF-α and IL-1β, and reduced I-κB expression in mice lung tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg i.p) more dramatically than by low dose (10 mg/kg i.p). Last, corilagin inhibits TGF-β1 production and α-SMA expression in lung tissue samples. Taken together, these findings confirmed that corilagin attenuates bleomycin-induced epithelial injury and fibrosis via inactivation of oxidative stress, proinflammatory cytokine release and NF-κB and TGF-β1 signaling. Corilagin may serve as a promising therapeutic agent for pulmonary fibrosis. PMID:24886817

  11. Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis

    PubMed Central

    Cruz, Fernanda Ferreira; Horta, Lucas Felipe Bastos; Maia, Lígia de Albuquerque; Lopes-Pacheco, Miquéias; da Silva, André Benedito; Morales, Marcelo Marco; Gonçalves-de-Albuquerque, Cassiano Felippe; Takiya, Christina Maeda; de Castro-Faria-Neto, Hugo Caire; Rocco, Patricia Rieken Macedo

    2016-01-01

    Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-α, interleukin-1β, transforming growth factor-β, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis. PMID:26789403

  12. Lung maturity in esophageal atresia: Experimental and clinical study.

    PubMed

    Fragoso, Ana Catarina; Martinez, Leopoldo; Estevão-Costa, José; Tovar, Juan A

    2015-08-01

    Esophageal atresia and tracheoesophageal fistula (EA-TEF) survivors suffer respiratory morbidity of unclear pathogenesis. Defective lung morphogenesis has been described in the rat model. This study examined fetal lung growth and maturity in rats and patients with EA-TEF. Pregnant rats received either adriamycin or vehicle. Control and adriamycin-exposed lungs, with and without EA-TEF, were weighed and processed for RT-PCR, DNA quantification, immunofluorescence and immunoblot analysis of TTF1, VEGF, Sp-B, and α-sma. Twenty human lungs were also processed for immunofluorescence and Alcian-blue staining. Lungs from fetuses with EA-TEF (E21) showed decreased total DNA; FGF7 and TTF1 mRNA expressions were upregulated at E15 and E18, respectively. Protein expression and immunofluorescent distribution of maturity markers were similar. Lungs from stillborns with EA-TEF showed decreased epithelial expression of Sp-B and VEGF whereas those from newborns tended to have less Sp-B and more VEGF and mucous glands. The lungs of rats with EA-TEF were hypoplastic but achieved near-normal maturity. Stillborns with EA-TEF exhibited an apparently disturbed differentiation of the airway epithelium. Newborns with EA-TEF demonstrated subtle differences in the expression of differentiation markers, and increased number of mucous glands that could influence postnatal respiratory adaptation and explain some respiratory symptoms of EA-TEF survivors. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Time- and compartment-resolved proteome profiling of the extracellular niche in lung injury and repair

    PubMed Central

    Schiller, Herbert B; Fernandez, Isis E; Burgstaller, Gerald; Schaab, Christoph; Scheltema, Richard A; Schwarzmayr, Thomas; Strom, Tim M; Eickelberg, Oliver; Mann, Matthias

    2015-01-01

    The extracellular matrix (ECM) is a key regulator of tissue morphogenesis and repair. However, its composition and architecture are not well characterized. Here, we monitor remodeling of the extracellular niche in tissue repair in the bleomycin-induced lung injury mouse model. Mass spectrometry quantified 8,366 proteins from total tissue and bronchoalveolar lavage fluid (BALF) over the course of 8 weeks, surveying tissue composition from the onset of inflammation and fibrosis to its full recovery. Combined analysis of proteome, secretome, and transcriptome highlighted post-transcriptional events during tissue fibrogenesis and defined the composition of airway epithelial lining fluid. To comprehensively characterize the ECM, we developed a quantitative detergent solubility profiling (QDSP) method, which identified Emilin-2 and collagen-XXVIII as novel constituents of the provisional repair matrix. QDSP revealed which secreted proteins interact with the ECM, and showed drastically altered association of morphogens to the insoluble matrix upon injury. Thus, our proteomic systems biology study assigns proteins to tissue compartments and uncovers their dynamic regulation upon lung injury and repair, potentially contributing to the development of anti-fibrotic strategies. PMID:26174933

  14. Time-Resolved In Situ Measurements During Rapid Alloy Solidification: Experimental Insight for Additive Manufacturing

    DOE PAGES

    McKeown, Joseph T.; Zweiacker, Kai; Liu, Can; ...

    2016-01-27

    In research and industrial environments, additive manufacturing (AM) of metals and alloys is becoming a pervasive technology, though significant challenges remain before widespread implementation of AM can be realized. In situ investigations of rapid alloy solidification with high spatial and temporal resolutions can provide unique experimental insight into microstructure evolution and kinetics that are relevant for AM processing. Hypoeutectic thin-film Al–Cu and Al–Si alloys were investigated using dynamic transmission electron microscopy to monitor pulsed-laser-induced rapid solidification across microsecond timescales. Solid–liquid interface velocities measured from time-resolved images revealed accelerating solidification fronts in both alloys. We observed microstructure evolution, solidification product, andmore » presence of a morphological instability at the solid–liquid interface in the Al–4 at.%Cu alloy are related to the measured interface velocities and small differences in composition that affect the thermophysical properties of the alloys. These time-resolved in situ measurements can inform and validate predictive modeling efforts for AM.« less

  15. Time-Resolved In Situ Measurements During Rapid Alloy Solidification: Experimental Insight for Additive Manufacturing

    SciTech Connect

    McKeown, Joseph T.; Zweiacker, Kai; Liu, Can; Coughlin, Daniel R.; Clarke, Amy J.; Baldwin, J. Kevin; Gibbs, John W.; Roehling, John D.; Imhoff, Seth D.; Gibbs, Paul J.; Tourret, Damien; Wiezorek, Jörg M. K.; Campbell, Geoffrey H.

    2016-01-27

    In research and industrial environments, additive manufacturing (AM) of metals and alloys is becoming a pervasive technology, though significant challenges remain before widespread implementation of AM can be realized. In situ investigations of rapid alloy solidification with high spatial and temporal resolutions can provide unique experimental insight into microstructure evolution and kinetics that are relevant for AM processing. Hypoeutectic thin-film Al–Cu and Al–Si alloys were investigated using dynamic transmission electron microscopy to monitor pulsed-laser-induced rapid solidification across microsecond timescales. Solid–liquid interface velocities measured from time-resolved images revealed accelerating solidification fronts in both alloys. We observed microstructure evolution, solidification product, and presence of a morphological instability at the solid–liquid interface in the Al–4 at.%Cu alloy are related to the measured interface velocities and small differences in composition that affect the thermophysical properties of the alloys. These time-resolved in situ measurements can inform and validate predictive modeling efforts for AM.

  16. Time-Resolved In Situ Measurements During Rapid Alloy Solidification: Experimental Insight for Additive Manufacturing

    NASA Astrophysics Data System (ADS)

    McKeown, Joseph T.; Zweiacker, Kai; Liu, Can; Coughlin, Daniel R.; Clarke, Amy J.; Baldwin, J. Kevin; Gibbs, John W.; Roehling, John D.; Imhoff, Seth D.; Gibbs, Paul J.; Tourret, Damien; Wiezorek, Jörg M. K.; Campbell, Geoffrey H.

    2016-03-01

    Additive manufacturing (AM) of metals and alloys is becoming a pervasive technology in both research and industrial environments, though significant challenges remain before widespread implementation of AM can be realized. In situ investigations of rapid alloy solidification with high spatial and temporal resolutions can provide unique experimental insight into microstructure evolution and kinetics that are relevant for AM processing. Hypoeutectic thin-film Al-Cu and Al-Si alloys were investigated using dynamic transmission electron microscopy to monitor pulsed-laser-induced rapid solidification across microsecond timescales. Solid-liquid interface velocities measured from time-resolved images revealed accelerating solidification fronts in both alloys. The observed microstructure evolution, solidification product, and presence of a morphological instability at the solid-liquid interface in the Al-4 at.%Cu alloy are related to the measured interface velocities and small differences in composition that affect the thermophysical properties of the alloys. These time-resolved in situ measurements can inform and validate predictive modeling efforts for AM.

  17. [Pathomorphology of lung changes caused by gramoxone poisoning. Human pathologic and animal experimental studies].

    PubMed

    Vadnay, I; Haraszti, A

    1988-01-01

    An account is given in this paper of changes caused by Gramoxone, a week killer, to the human lung as well as to experimental material. The process of damage was found to depend on the amount of toxic substance involved and on the route of uptake. Fibrosis, eventually, is the greatest danger. Intraperitoneal application leads to squamous epithelium metaplasia in the lung.

  18. Beneficial effects of synthetic KL₄ surfactant in experimental lung transplantation.

    PubMed

    Sáenz, A; Alvarez, L; Santos, M; López-Sánchez, A; Castillo-Olivares, J L; Varela, A; Segal, R; Casals, C

    2011-04-01

    The aim of this study was to investigate whether intratracheal administration of a new synthetic surfactant that includes the cationic, hydrophobic 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL₄), might be effective in reducing ischaemia-reperfusion injury after lung transplantation. Single left lung transplantation was performed in Landrace pigs 22 h post-harvest. KL₄ surfactant at a dose of 25 mg total phospholipid·kg body weight⁻¹ (2.5 mL·kg body weight⁻¹) was instilled at 37°C to the donor left lung (n = 8) prior to explantation. Saline (2.5 mL·kg body weight⁻¹; 37°C) was instilled into the donor left lung of the untreated group (n = 6). Lung function in recipients was measured during 2 h of reperfusion. Recipient left lung bronchoalveolar lavage (BAL) provided native cytometric, inflammatory marker and surfactant data. KL(4) surfactant treatment recovered oxygen levels in the recipient blood (mean ± sd arterial oxygen tension/inspiratory oxygen fraction 424 ± 60 versus 263 ± 101 mmHg in untreated group; p=0.01) and normalised alveolar-arterial oxygen tension difference. Surfactant biophysical function was also recovered in KL₄ surfactant-treated lungs. This was associated with decreased C-reactive protein levels in BAL, and recovery of surfactant protein A content, normalised protein/phospholipid ratios, and lower levels of both lipid peroxides and protein carbonyls in large surfactant aggregates. These findings suggest an important protective role for KL₄ surfactant treatment in lung transplantation.

  19. Alternative solution for ex vivo lung perfusion, experimental study on donated human lungs non-accepted for transplantation.

    PubMed

    Fernandes, Lucas Matos; Mariani, Alessandro Wasum; Medeiros, Israel Lopes de; Samano, Marcos Naoyuki; Abdalla, Luís Gustavo; Correia, Aristides Tadeu; Nepomuceno, Natália Aparecida; Canzian, Mauro; Pêgo-Fernandes, Paulo Manuel

    2015-05-01

    To evaluate a new perfusate solution to be used for ex vivo lung perfusion. Randomized experimental study using lungs from rejected brain-dead donors harvested and submitted to 1 hour of ex vivo lung perfusion (EVLP) using mainstream solution or the alternative. From 16 lungs blocs tested, we found no difference on weight after EVLP: Steen group (SG) = 1,097±526g; Alternative Perfusion Solution (APS) = 743±248g, p=0.163. Edema formation, assessed by Wet/dry weigh ratio, was statistically higher on the Alternative Perfusion Solution group (APS = 3.63 ± 1.26; SG = 2.06 ± 0.28; p = 0.009). No difference on PaO2 after EVLP (SG = 498±37.53mmHg; APS = 521±55.43mmHg, p=0.348, nor on histological analyses: pulmonary injury score: SG = 4.38±1.51; APS = 4.50±1.77, p=0.881; apoptotic cells count after perfusion: SG = 2.4 ± 2.0 cells/mm2; APS = 4.8 ± 6.9 cells/mm2; p = 0.361). The ex vivo lung perfusion using the alternative perfusion solution showed no functional or histological differences, except for a higher edema formation, from the EVLP using Steen Solution(r) on lungs from rejected brain-dead donors.

  20. Effects of exogenous surfactant on the non-heart-beating donor lung graft in experimental lung transplantation - a stereological study.

    PubMed

    Herrmann, Gudrun; Knudsen, Lars; Madershahian, Navid; Mühlfeld, Christian; Frank, Konrad; Rahmanian, Parwis; Wahlers, Thorsten; Wittwer, Thorsten; Ochs, Matthias

    2014-05-01

    The use of non-heart-beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non-SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design-based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham-operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non-SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron-chovascular connective tissue. Regarding intra-alveolar oedema, no statistically significant difference could be found between SF and non-SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart-beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed are

  1. The left lung is preferentially targeted during experimental paracoccidioidomycosis in C57BL/6 mice

    PubMed Central

    Tristão, F.S.M.; Rocha, F.A.; Dias, F.C.; Rossi, M.A.; Silva, J.S.

    2013-01-01

    Paracoccidioidomycosis (PCM) is a chronic systemic mycosis caused by the inhalation of the thermally dimorphic fungus Paracoccidioides brasiliensis as well as the recently described P. lutzii. Because the primary infection occurs in the lungs, we investigated the differential involvement of the right and left lungs in experimental P. brasiliensis infection. Lungs were collected from C57BL/6 mice at 70 days after intravenous infection with 1×106 yeast cells of a virulent strain of P. brasiliensis (Pb18). The left lung, which in mice is smaller and has fewer lobes than the right lung, yielded increased fungal recovery associated with a predominant interleukin-4 response and diminished synthesis of interferon-γ and nitric oxide compared with the right lung. Our data indicate differential involvement of the right and left lungs during experimental PCM. This knowledge emphasizes the need for an accurate, standardized protocol for tissue collection during studies of experimental P. brasiliensis infection, since experiments using the same lungs favor the collection of comparable data among different mice. PMID:24141611

  2. Spatially resolved and observer-free experimental quantification of spatial resolution in tomographic images

    SciTech Connect

    Tsekenis, S. A.; McCann, H.; Tait, N.

    2015-03-15

    We present a novel framework and experimental method for the quantification of spatial resolution of a tomography system. The framework adopts the “black box” view of an imaging system, considering only its input and output. The tomography system is locally stimulated with a step input, viz., a sharp edge. The output, viz., the reconstructed images, is analysed by Fourier decomposition of their spatial frequency components, and the local limiting spatial resolution is determined using a cut-off threshold. At no point is an observer involved in the process. The framework also includes a means of translating the quantification region in the imaging space, thus creating a spatially resolved map of objectively quantified spatial resolution. As a case-study, the framework is experimentally applied using a gaseous propane phantom measured by a well-established chemical species tomography system. A spatial resolution map consisting of 28 regions is produced. In isolated regions, the indicated performance is 4-times better than that suggested in the literature and varies by 57% across the imaging space. A mechanism based on adjacent but non-interacting beams is hypothesised to explain the observed behaviour. The mechanism suggests that, as also independently concluded by other methods, a geometrically regular beam array maintains maximum objectivity in reconstructions. We believe that the proposed framework, methodology, and findings will be of value in the design and performance evaluation of tomographic imaging arrays and systems.

  3. Experimental Evidence of Mechanical Isotropy in Porcine Lung Parenchyma

    PubMed Central

    Weed, Benjamin; Patnaik, Sourav; Rougeau-Browning, Mary; Brazile, Bryn; Liao, Jun; Prabhu, Raj; Williams, Lakiesha N.

    2015-01-01

    Pulmonary injuries are a major source of morbidity and mortality associated with trauma. Trauma includes injuries associated with accidents and falls as well as blast injuries caused by explosives. The prevalence and mortality of these injuries has made research of pulmonary injury a major priority. Lungs have a complex structure, with multiple types of tissues necessary to allow successful respiration. The soft, porous parenchyma is the component of the lung which contains the alveoli responsible for gas exchange. Parenchyma is also the portion which is most susceptible to traumatic injury. Finite element simulations are an important tool for studying traumatic injury to the human body. These simulations rely on material properties to accurately recreate real world mechanical behaviors. Previous studies have explored the mechanical properties of lung tissues, specifically parenchyma. These studies have assumed material isotropy but, to our knowledge, no study has thoroughly tested and quantified this assumption. This study presents a novel methodology for assessing isotropy in a tissue, and applies these methods to porcine lung parenchyma. Briefly, lung parenchyma samples were dissected so as to be aligned with one of the three anatomical planes, sagittal, frontal, and transverse, and then subjected to compressive mechanical testing. Stress-strain curves from these tests were statistically compared by a novel method for differences in stresses and strains at percentages of the curve. Histological samples aligned with the anatomical planes were also examined by qualitative and quantitative methods to determine any differences in the microstructural morphology. Our study showed significant evidence to support the hypothesis that lung parenchyma behaves isotropically.

  4. Resolution of experimental lung injury by Monocyte-derived inducible nitric oxide synthase (iNOS)

    PubMed Central

    D’Alessio, Franco R.; Tsushima, Kenji; Aggarwal, Neil R.; Mock, Jason R.; Eto, Yoshiki; Garibaldi, Brian T.; Files, Daniel C.; Avalos, Claudia R.; Rodriguez, Jackie V.; Waickman, Adam T.; Reddy, Sekhar P.; Pearse, David B.; Sidhaye, Venkataramana K.; Hassoun, Paul M.; Crow, Michael T.; King, Landon S.

    2012-01-01

    While early events in the pathogenesis of acute lung injury (ALI) have been defined, little is known about mechanisms mediating resolution. To search for determinants of resolution, we exposed wild type (WT) mice to intratracheal lipopolysacaccharide (i.t. LPS) and assessed the response at intervals to day 10, when injury had resolved. Inducible nitric oxide synthase (iNOS) was significantly upregulated in the lung at day 4 after LPS. When iNOS−/− mice were exposed to i.t. LPS, early lung injury was attenuated, however recovery was markedly impaired compared to wild type (WT) mice. iNOS−/− mice had increased mortality and sustained increases in markers of lung injury. Adoptive transfer of WT (iNOS+/+) bone marrow-derived monocytes or direct adenoviral gene delivery of iNOS into injured iNOS−/− mice restored resolution of ALI. Irradiated bone marrow chimeras confirmed the protective effects of myeloid-derived iNOS, but not of epithelial iNOS. Alveolar macrophages exhibited sustained expression of co-signalling molecule CD86 in iNOS−/− mice compared to WT mice. Antibody-mediated blockade of CD86 in iNOS−/− mice improved survival and enhanced resolution of lung inflammation. Our findings show that monocyte-derived iNOS plays a pivotal role in mediating resolution of ALI by modulating lung immune responses, thus facilitating clearance of alveolar inflammation and promoting lung repair. PMID:22844117

  5. Mechanism of tumour vascularization in experimental lung metastases.

    PubMed

    Szabo, Vanessza; Bugyik, Edina; Dezso, Katalin; Ecker, Nora; Nagy, Peter; Timar, Jozsef; Tovari, Jozsef; Laszlo, Viktoria; Bridgeman, Victoria L; Wan, Elaine; Frentzas, Sophia; Vermeulen, Peter B; Reynolds, Andrew R; Dome, Balazs; Paku, Sandor

    2015-02-01

    The appearance of lung metastases is associated with poor outcome and the management of patients with secondary pulmonary tumours remains a clinical challenge. We examined the vascularization process of lung metastasis in six different preclinical models and found that the tumours incorporated the pre-existing alveolar capillaries (ie vessel co-option). During the initial phase of vessel co-option, the incorporated capillaries were still sheathed by pneumocytes, but these incorporated vessels subsequently underwent different fates dependent on the model. In five of the models examined (B16, HT1080, HT25, C26, and MAT B-III), the tumour cells gradually stripped the pneumocytes from the vessels. These dissected pneumocytes underwent fragmentation, but the incorporated microvessels survived. In the sixth model (C38), the tumour cells failed to invade the alveolar walls. Instead, they induced the development of vascularized desmoplastic tissue columns. Finally, we examined the process of arterialization in lung metastases and found that they became arterialized when their diameter grew to exceed 5 mm. In conclusion, our data show that lung metastases can vascularize by co-opting the pulmonary microvasculature. This is likely to have important clinical implications, especially with respect to anti-angiogenic therapies.

  6. Experimental pressure-temperature phase diagram of boron: resolving the long-standing enigma

    PubMed Central

    Parakhonskiy, Gleb; Dubrovinskaia, Natalia; Bykova, Elena; Wirth, Richard; Dubrovinsky, Leonid

    2011-01-01

    Boron, discovered as an element in 1808 and produced in pure form in 1909, has still remained the last elemental material, having stable natural isotopes, with the ground state crystal phase to be unknown. It has been a subject of long-standing controversy, if α-B or β-B is the thermodynamically stable phase at ambient pressure and temperature. In the present work this enigma has been resolved based on the α-B-to- β-B phase boundary line which we experimentally established in the pressure interval of ∼4 GPa to 8 GPa and linearly extrapolated down to ambient pressure. In a series of high pressure high temperature experiments we synthesised single crystals of the three boron phases (α-B, β-B, and γ-B) and provided evidence of higher thermodynamic stability of α-B. Our work opens a way for reproducible synthesis of α-boron, an optically transparent direct band gap semiconductor with very high hardness, thermal and chemical stability. PMID:22355614

  7. Therapeutic Transcutaneous Immunization with a Band-Aid Vaccine Resolves Experimental Otitis Media

    PubMed Central

    Novotny, Laura A.; Clements, John D.

    2015-01-01

    Transcutaneous immunization (TCI) is a noninvasive strategy to induce protective immune responses. We describe TCI with a band-aid vaccine placed on the postauricular skin to exploit the unique organization of the stratum corneum and to promote the development of immune responses to resolve active experimental otitis media due to nontypeable Haemophilus influenzae (NTHI). This therapeutic immunization strategy induced significantly earlier resolution of middle ear fluid and rapid eradication of both planktonic and mucosal biofilm-resident NTHI within 7 days after receipt of the first immunizing band-aid vaccine. Efficacy was ascribed to the homing of immunogen-bearing cutaneous dendritic cells to the nasal-associated lymphoid tissue, induction of polyfunctional CD4+ T cells, and the presence of immunogen-specific IgM and IgG within the middle ear. TCI using band-aid vaccines could expand the use of traditional parenteral preventative vaccines to include treatment of active otitis media, in addition to other diseases of the respiratory tract due to NTHI. PMID:26018536

  8. Sparse view Compton scatter tomography with energy resolved data: experimental and simulation results

    NASA Astrophysics Data System (ADS)

    Desmal, Abdulla; Tracey, Brian H.; Rezaee, Hamideh; Miller, Eric L.; Schubert, Jeffrey R.; Denker, Jeff; Couture, Aaron

    2017-05-01

    X-ray inspection systems play a critical role in many non-destructive testing and security applications, with systems typically measuring attenuation during transmission along straight-line paths connecting sources and detectors. Computed tomography (CT) systems can provide higher-quality images than single- or dual-view systems, but the need to measure many projections through the scene increases system complexity and cost. We seek to maximize the image quality of sparse-view (few-view) systems by combining attenuation data with measurements of Compton-scattered photons, that deflect after scattering and arrive at detectors via broken ray paths that provide additional sampling of the scene. The work below presents experimental validation of a singlescatter forward model for Compton-scatter data measured with energy-resolving detectors, and demonstrates a reconstruction algorithm that combines both attenuation and scatter measurements. The results suggest that including Compton-scattered data in the reconstruction process can improve image quality for few-view systems.

  9. Experimental Lung Cancer Drug Shows Early Promise | Poster

    Cancer.gov

    By Frank Blanchard, Staff Writer A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for safety and efficacy in Phase I and II clinical trials.

  10. Experimental Lung Cancer Drug Shows Early Promise | Poster

    Cancer.gov

    By Frank Blanchard, Staff Writer A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for safety and efficacy in Phase I and II clinical trials.

  11. Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo

    PubMed Central

    Lehmann, Mareike; Korfei, Martina; Mutze, Kathrin; Klee, Stephan; Skronska-Wasek, Wioletta; Alsafadi, Hani N.; Ota, Chiharu; Costa, Rita; Schiller, Herbert B.; Lindner, Michael; Wagner, Darcy E.; Günther, Andreas

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and the impact of senolytic drugs on senescent lung cells and fibrosis remain unknown. Here we demonstrate that lung epithelial cells exhibit increased P16 and P21 expression as well as senescence-associated β-galactosidase activity in experimental and human lung fibrosis tissue and primary cells. Primary fibrotic mouse alveolar epithelial type (AT)II cells secreted increased amounts of senescence-associated secretory phenotype (SASP) factors in vitro, as analysed using quantitative PCR, mass spectrometry and ELISA. Importantly, pharmacological clearance of senescent cells by induction of apoptosis in fibrotic ATII cells or ex vivo three-dimensional lung tissue cultures reduced SASP factors and extracellular matrix markers, while increasing alveolar epithelial markers. These data indicate that alveolar epithelial cell senescence contributes to lung fibrosis development and that senolytic drugs may be a viable therapeutic option for IPF. PMID:28775044

  12. Blunted Hypoxic Pulmonary Vasoconstriction in Experimental Neonatal Chronic Lung Disease

    PubMed Central

    Rey-Parra, Gloria Juliana; Archer, Stephen L.; Bland, Richard D.; Albertine, Kurt H.; Carlton, David P.; Cho, Soo-Chul; Kirby, Beth; Haromy, Al; Eaton, Farah; Wu, Xichen; Thébaud, Bernard

    2008-01-01

    Rationale: Neonatal chronic lung disease (CLD), caused by prolonged mechanical ventilation (MV) with O2-rich gas, is the most common cause of long-term hospitalization and recurrent respiratory illness in extremely premature infants. Recurrent episodes of hypoxemia and associated ventilator adjustments often lead to worsening CLD. The mechanism that causes these hypoxemic episodes is unknown. Hypoxic pulmonary vasoconstriction (HPV), which is partially controlled by O2-sensitive voltage-gated potassium (Kv) channels, is an important adaptive response to local hypoxia that helps to match perfusion and ventilation in the lung. Objectives: To test the hypothesis that chronic lung injury (CLI) impairs HPV. Methods: We studied preterm lambs that had MV with O2-rich gas for 3 weeks and newborn rats that breathed 95%-O2 for 2 weeks, both of which resulted in airspace enlargement and pulmonary vascular changes consistent with CLD. Measurements and Main Results: HPV was attenuated in preterm lambs with CLI after 2 weeks of MV and in newborn rats with CLI after 2 weeks of hyperoxia. HPV and constriction to the Kv1.x-specific inhibitor, correolide, were preferentially blunted in excised distal pulmonary arteries (dPAs) from hyperoxic rats, whose dPAs exhibited decreased Kv1.5 and Kv2.1 mRNA and K+ current. Intrapulmonary gene transfer of Kv1.5, encoding the ion channel that is thought to trigger HPV, increased O2-sensitive K+ current in cultured smooth muscle cells from rat dPAs, and restored HPV in hyperoxic rats. Conclusions: Reduced expression/activity of O2-sensitive Kv channels in dPAs contributes to blunted HPV observed in neonatal CLD. PMID:18511704

  13. Resolving Key Uncertainties in Subsurface Energy Recovery: One Role of In Situ Experimentation and URLs (Invited)

    NASA Astrophysics Data System (ADS)

    Elsworth, D.

    2013-12-01

    Significant uncertainties remain and influence the recovery of energy from the subsurface. These uncertainties include the fate and transport of long-lived radioactive wastes that result from the generation of nuclear power and have been the focus of an active network of international underground research laboratories dating back at least 35 years. However, other nascent carbon-free energy technologies including conventional and EGS geothermal methods, carbon-neutral methods such as carbon capture and sequestration and the utilization of reduced-carbon resources such as unconventional gas reservoirs offer significant challenges in their effective deployment. We illustrate the important role that in situ experiments may play in resolving behaviors at extended length- and time-scales for issues related to chemical-mechanical interactions. Significantly, these include the evolution of transport and mechanical characteristics of stress-sensitive fractured media and their influence of the long-term behavior of the system. Importantly, these interests typically relate to either creating reservoirs (hydroshearing in EGS reservoirs, artificial fractures in shales and coals) or maintaining seals at depth where the permeating fluids may include mixed brines, CO2, methane and other hydrocarbons. Critical questions relate to the interaction of these various fluid mixtures and compositions with the fractured substrate. Important needs are in understanding the roles of key processes (transmission, dissolution, precipitation, sorption and dynamic stressing) on the modification of effective stresses and their influence on the evolution of permeability, strength and induced seismicity on the resulting development of either wanted or unwanted fluid pathways. In situ experimentation has already contributed to addressing some crucial issues of these complex interactions at field scale. Important contributions are noted in understanding the fate and transport of long-lived wastes

  14. Photophysics of 1-aminonaphthalene: a theoretical and time-resolved experimental study.

    PubMed

    Montero, Raúl; Longarte, Asier; Conde, Alvaro Peralta; Redondo, Carolina; Castaño, Fernando; González-Ramírez, Israel; Giussani, Angelo; Serrano-Andrés, Luis; Merchán, Manuela

    2009-12-03

    The photophysics of 1-aminonaphthalene (1-napthylamine, AMN) has been investigated on the basis of a constructive experimental-theoretical interplay derived from time-resolved measurements and high-level quantum-chemical ab initio CASPT2//CASSCF calculations. Transient ionization signals at femtosecond resolution were collected for AMN cold isolated molecules following excitation from the vibrationless ground level to a number of vibrational states (within the pump resolution) in the lowest accessible excited state and further multiphoton ionization probing at 500, 800, and 1300 nm. Theory predicts two pipi* states, (1)L(b) and (1)L(a), as the lowest singlet electronic excitations, with adiabatic transitions from S(0) at 3.50 and 3.69 eV, respectively. Since the associated oscillator strength for the lowest transition is exceedingly small, the (1)L(b) state is not expected to become populated significantly and the (1)L(a) state appears as the main protagonist of the AMN photophysics. Though calculations foresee a surface crossing between (1)L(a) and the lower (1)L(b) states, no dynamical signature of it is observed in the time-dependent measurements. In the relaxation of (1)L(a), the radiant emission competes with the intersystem crossing and internal conversion channels. The rates of these mechanisms have been determined at different excitation energies. The internal conversion is mediated by a (1)L(a)/S(0) conical intersection located 0.7 eV above the (1)L(a) minimum. The relaxation of a higher-lying singlet excited state, observed above 40 000 cm(-1) (4.96 eV) and calculated at 5.18 eV, has been also explored.

  15. Experimental drowning lung images on postmortem CT - Difference between sea water and fresh water.

    PubMed

    Hyodoh, Hideki; Terashima, Ryuji; Rokukawa, Masumi; Shimizu, Junya; Okazaki, Shunichiro; Mizuo, Keisuke; Watanabe, Satoshi

    2016-03-01

    Experimental drowning models were prepared to investigate the time-related course of lung changes using postmortem CT. This study was approved by our institutional animal ethics committee. Fifteen NZW rabbits (female fifteen, 2.6-4.3 (mean 3.3)kg) were divided into 3 groups: fresh water drowning (FRESH), sea water drowning (SEA), and sea water drowning with anterior chest compression (ACC). All individuals were examined by CT (Aquilion CX, Toshiba, Japan) on postmortem time course. The rabbit's head was submerged in a water bath for a total of 10 min. In ACC, cardiopulmonary resuscitation was performed for 2 min, additionally. The percentage of aerated lung volumes (%ALV=100 (aerated lung volume/total lung volume)) were statistically evaluated and the lung CT image patterns and pleural fluid appearance time were investigated. All lungs had decreased their %ALV within 24h, and there were no statistical differences in and among the 3 groups. After 36 h, %ALV tended to increase in all groups, and only ACC presented a statistical difference between 1h and 36 h (p<0.005). On postmortem lung CT, all lungs presented ground-glass opacity with interstitial thickening spread pattern (100%) and no pattern change during the follow-up period. After presenting pleural space fluid collection, the %ALV tended to increase. There were no differences among FRESH, SEA, and ACC in %ALV within 24h. Only ground-glass opacity could be detected on postmortem lung CT, experimentally. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. The tyrosine kinase inhibitor dasatinib reduces lung inflammation and remodelling in experimental allergic asthma

    PubMed Central

    da Silva, AL; Magalhães, RF; Branco, VC; Silva, JD; Cruz, FF; Marques, PS; Ferreira, TPT; Morales, MM; Martins, MA; Olsen, PC

    2016-01-01

    Background and Purpose Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in understanding of its pathophysiology, asthma remains a major public health problem, and new therapeutic strategies are urgently needed. In this context, we sought to ascertain whether treatment with the TK inhibitor dasatinib might repair inflammatory and remodelling processes, thus improving lung function, in a murine model of asthma. Experimental Approach Animals were sensitized and subsequently challenged, with ovalbumin (OVA) or saline. Twenty‐four hours after the last challenge, animals were treated with dasatinib, dexamethasone, or saline, every 12 h for 7 consecutive days. Twenty‐four hours after the last treatment, the animals were killed, and data were collected. Lung structure and remodelling were evaluated by morphometric analysis, immunohistochemistry, and transmission electron microscopy of lung sections. Inflammation was assessed by cytometric analysis and ELISA, and lung function was evaluated by invasive whole‐body plethysmography. Key Results In OVA mice, dasatinib, and dexamethasone led to significant reductions in airway hyperresponsiveness. Dasatinib was also able to attenuate alveolar collapse, contraction index, and collagen fibre deposition, as well as increasing elastic fibre content, in OVA mice. Concerning the inflammatory process, dasatinib reduced inflammatory cell influx to the airway and lung‐draining mediastinal lymph nodes, without inducing the thymic atrophy promoted by dexamethasone. Conclusions and Implications In this model of allergic asthma, dasatinib effectively blunted the inflammatory and remodelling processes in asthmatic lungs, enhancing airway repair and thus improving lung mechanics. PMID:26989986

  17. Experimental station for laser-based picosecond time-resolved x-ray absorption near-edge spectroscopy

    NASA Astrophysics Data System (ADS)

    Dorchies, F.; Fedorov, N.; Lecherbourg, L.

    2015-07-01

    We present an experimental station designed for time-resolved X-ray Absorption Near-Edge Spectroscopy (XANES). It is based on ultrashort laser-plasma x-ray pulses generated from a table-top 100 mJ-class laser at 10 Hz repetition rate. A high transmission (10%-20%) x-ray beam line transport using polycapillary optics allows us to set the sample in an independent vacuum chamber, providing high flexibility over a wide spectral range from 0.5 up to 4 keV. Some XANES spectra are presented, demonstrating 1% noise level in only ˜1 mn and ˜100 cumulated laser shots. Time-resolved measurements are reported, indicating that the time resolution of the entire experimental station is 3.3 ± 0.6 ps rms.

  18. Aspirin-triggered resolvin D1 is produced during self-resolving gram-negative bacterial pneumonia and regulates host immune responses for the resolution of lung inflammation

    PubMed Central

    Abdulnour, Raja Elie E.; Sham, Ho Pan; Douda, David N.; Colas, Romain A.; Dalli, Jesmond; Bai, Yan; Ai, Xingbin; Serhan, Charles N.; Levy, Bruce D.

    2016-01-01

    Bacterial pneumonia is a leading cause of morbidity and mortality worldwide. Host responses to contain infection and mitigate pathogen-mediated lung inflammation are critical for pneumonia resolution. Aspirin-triggered resolvin D1 (AT-RvD1; 7S,8R,17R trihydroxy-4Z,9E,11E,13Z,15E,19Z docosahexaenoic acid) is a lipid mediator that displays organ protective actions in sterile lung inflammation, and regulates pathogen-initiated cellular responses. Here, in a self-resolving murine model of Escherichia coli pneumonia, lipid mediator metabololipidomics performed on lungs obtained at baseline, 24 hours and 72 hours after infection uncovered temporal regulation of endogenous AT-RvD1 production. Early treatment with exogenous AT-RvD1 (1 hr post-infection) enhanced clearance of E.coli and Pseudomonas aeruginosa in vivo, and lung macrophage phagocytosis of fluorescent bacterial particles ex vivo. Characterization of macrophage subsets in the alveolar compartment during pneumonia identified efferocytosis by infiltrating macrophages (CD11bHi CD11cLow) and exudative macrophages (CD11bHi CD11cHi). AT-RvD1 increased efferocytosis by these cells ex vivo, and accelerated neutrophil clearance during pneumonia in vivo. These anti-bacterial and pro-resolving actions of AT-RvD1 were additive to antibiotic therapy. Taken together, these findings suggest that the pro-resolving actions of AT-RvD1 during pneumonia represent a novel host-directed therapeutic strategy to complement the current antibiotic centered approach to combatting infections. PMID:26647716

  19. Modeling Mycobacterium tuberculosis early granuloma formation in experimental human lung tissue.

    PubMed

    Parasa, Venkata Ramanarao; Rahman, Muhammad Jubayer; Ngyuen Hoang, Anh Thu; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria

    2014-02-01

    The widely used animal models for tuberculosis (TB) display fundamental differences from human TB. Therefore, a validated model that recapitulates human lung TB is attractive for TB research. Here, we describe a unique method for establishment of TB infection in an experimental human lung tissue model. The model is based on cell lines derived from human lungs and primary macrophages from peripheral blood, and displays characteristics of human lung tissue, including evenly integrated macrophages throughout the epithelium, production of extracellular matrix, stratified epithelia and mucus secretion. Establishment of experimental infection in the model tissue with Mycobacterium tuberculosis, the bacterium that causes TB, resulted in clustering of macrophages at the site of infection, reminiscent of early TB granuloma formation. We quantitated the extent of granuloma formation induced by different strains of mycobacteria and validated our model against findings in other TB models. We found that early granuloma formation is dependent on ESAT-6, which is secreted via the type VII secretion machinery of virulent mycobacteria. Our model, which can facilitate the discovery of the interactions between mycobacteria and host cells in a physiological environment, is the first lung tissue model described for TB.

  20. Effects of surfactant/budesonide therapy on oxidative modifications in the lung in experimental meconium-induced lung injury.

    PubMed

    Mikolka, P; Kopincova, J; Tomcikova Mikusiakova, L; Kosutova, P; Antosova, M; Calkovska, A; Mokra, D

    2016-02-01

    Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS. Meconium suspension (25 mg/ml, 4 ml/kg) was instilled into the trachea of young rabbits, whereas one group of animals received saline instead of meconium (C group, n = 6). In meconium-instilled animals, respiratory failure developed within 30 min. Then, meconium-instilled animals were divided into 3 groups according to therapy (n = 6 each): with surfactant therapy (M + S group), with surfactant + budesonide therapy (M + S + B), and without therapy (M group). Surfactant therapy consisted of two bronchoalveolar lavages (BAL) with diluted surfactant (Curosurf, 5 mg phospholipids/ml, 10 ml/kg) followed by undiluted surfactant (100 mg phospholipids/kg), which was in M + S + B group enriched with budesonide (Pulmicort, 0.5 mg/ml). Animals were oxygen-ventilated for additional 5 hours. At the end of experiment, blood sample was taken for differential white blood cell (WBC) count. After euthanizing animals, left lung was saline-lavaged and cell differential in BAL was determined. Oxidative damage, i.e. oxidation of lipids (thiobarbituric acid reactive substance (TBARS) and conjugated dienes) and proteins (dityrosine and lysine-lipoperoxidation products) was estimated in lung homogenate and isolated mitochondria. Total antioxidant capacity was evaluated in lung homogenate and plasma. Meconium instillation increased transmigration of neutrophils and production of free

  1. Comparison of Numerical and Experimental Time-Resolved Near-Field Hall Thruster Plasma Properties

    DTIC Science & Technology

    2012-07-20

    26.4+/-0.3 s 38 KHz Distribution A: Approved for public release; distribution unlimited. Discharge Currect (AC) Passive inductive probe Band pass...other provision of law , no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a...Resolved Near-Field Hall Thruster 5b. GRANT NUMBER Plasma Properties 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Gonzales, A.E.; Scharfe, M.K

  2. Experimental measurement of spatially resolved electron density in a filament of a pulsed positive streamer discharge in water

    SciTech Connect

    Wen, Xiao Qiong; Niu, Zhi Wen; Ren, Chun-Sheng; Hou, Bo

    2015-06-29

    By combining a high-speed frame camera with a monochromator, the spatially resolved optical emission spectrum of hydrogen α line in a single filament of a pulsed positive streamer discharge in water has been experimentally measured. The spatially resolved electron densities in a single filament of a pulsed positive streamer discharge in water with a conductivity of 200 μS/cm were investigated. During the experiment, the average energy per pulse of discharge was 90.6 ± 13.6 mJ. The results show that the electron density in the streamer filament is 10{sup 17–18}/cm{sup 3}, and present a decreasing tendency along the axial direction of the streamer filament with increasing distance from the tip of the anode.

  3. Experimental tests of different solutions to the diffusion equation for optical characterization of scattering media by time-resolved transmittance.

    PubMed

    Delfino, I; Lepore, M; Indovina, P L

    1999-07-01

    A detailed investigation of the use of time-resolved trasmittance for the optical characterization of scattering media by use of different analytical solutions to the diffusion equation has been performed. A femtosecond Ti:sapphire laser working at 800 nm and a streak camera with a time resolution of a few picoseconds were employed. Different latex and Intralipid solutions as well as biological samples were investigated. Reduced scattering coefficients were evaluated, and good agreement with the Mie predictions was found. An estimation of the order of magnitude of the absorption coefficient was obtained for the low-absorbance samples examined. These studies confirm experimentally that time-resolved trasmittance can be employed usefully for evaluating s values of thick scattering samples when a proper theoretical description that takes into account realistic boundary conditions is used.

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

    PubMed

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

    2013-05-01

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

  5. Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

    PubMed Central

    Palozza, Paola; Simone, Rossella E.; Catalano, Assunta; Mele, Maria Cristina

    2011-01-01

    Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk. PMID:24212813

  6. Aromatase inhibitors decrease radiation-induced lung fibrosis: Results of an experimental study.

    PubMed

    Altinok, A Y; Yildirim, S; Altug, T; Sut, N; Ober, A; Ozsahin, E M; Azria, D; Bese, N S

    2016-08-01

    In experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Furthermore, aromatase inhibitors (AI) have been shown to be superior to TAM in the adjuvant setting and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation in other studies. In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats. 60 female wistar- albino rats were divided into 6 groups: Control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F). RT consisted of 30 Gy in 10 fractions to both lungs with an anterior field at 2 cm depth. Equivalent doses for 60 kg adult dose per day of TAM, ANA, LET, and EXE were calculated according to the mean weight of rats and orally administrated with a feeding tube. Percentage of lung with fibrosis was quantified with image analysis of histological sections of the lung. The mean score values were calculated for each group. the significance of the differences among groups were calculated using one way ANOVA test and Tukey HSD post-hoc test. Mean values of fibrosis were 1.7, 5.9, 6.7, 2.5, 2 and 2.2 for groups A, B, C, D, E, and F, respectively (p = 0.000). TAM increased RT-induced lung fibrosis but without statistical significance. Groups treated with RT + AI showed significantly less lung fibrosis than groups treated with RT alone or RT + TAM (p = 0.000). RT + AI groups showed nearly similar RT-induced lung fibrosis than control group. In this study, we found that AI decreased RT-induced lung fibrosis to the control group level suggesting protective effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Gas density alters expiratory time constants before and after experimental lung injury.

    PubMed

    Henderson, William R; Molgat-Seon, Yannick; Dominelli, Paolo B; Brasher, Penelope M A; Griesdale, Donald E G; Foster, Glen E; Yacyshyn, Alexandra; Ayas, Najib T; Sheel, A William

    2015-10-01

    What is the central question of this study? Does the induction of a model of lung injury affect the expiratory time constant (τE) in terms of either total duration or morphology? Does ventilation with gases of different densities alter the duration or morphology of τE either before or after injury? What is the main finding and its importance? The use of sulfur hexafluoride in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both nitrogen and helium mixtures. Sulfur hexafluoride mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with nitrogen and helium mixtures. Acute lung injury is characterized by regional heterogeneity of lung resistance and elastance that may lead to regional heterogeneity of expiratory time constants (τE). We hypothesized that increasing airflow resistance by using inhaled sulfur hexafluoride (SF6) would lengthen time constants and decrease their heterogeneity in an experimental model of lung injury when compared with nitrogen or helium mixtures. To overcome the limitations of a single-compartment model, we employed a multisegment model of expiratory gas flow. An experimental model of lung injury was created using intratracheal injection of sodium polyacrylate in anaesthetized and mechanically ventilated female Yorkshire-cross pigs (n = 7). The animals were ventilated with 50% O2 and the remaining 50% as nitrogen (N2), helium (He) or sulfur hexafluoride (SF6). Values for τE decreased with injury and were more variable after injury than before (P < 0.001). Values for τE increased throughout expiration both before and after injury, and the rate of increase in τE was lessened by SF6 (P < 0.001 when compared with N2 both before and after injury). Altering the inhaled gas density did not affect indices of oxygenation, dead space or shunt. The use of SF6 in ventilating gas mixtures lengthens

  8. Experimental estimation of the photons visiting probability profiles in time-resolved diffuse reflectance measurement.

    PubMed

    Sawosz, P; Kacprzak, M; Weigl, W; Borowska-Solonynko, A; Krajewski, P; Zolek, N; Ciszek, B; Maniewski, R; Liebert, A

    2012-12-07

    A time-gated intensified CCD camera was applied for time-resolved imaging of light penetrating in an optically turbid medium. Spatial distributions of light penetration probability in the plane perpendicular to the axes of the source and the detector were determined at different source positions. Furthermore, visiting probability profiles of diffuse reflectance measurement were obtained by the convolution of the light penetration distributions recorded at different source positions. Experiments were carried out on homogeneous phantoms, more realistic two-layered tissue phantoms based on the human skull filled with Intralipid-ink solution and on cadavers. It was noted that the photons visiting probability profiles depend strongly on the source-detector separation, the delay between the laser pulse and the photons collection window and the complex tissue composition of the human head.

  9. Experimental estimation of the photons visiting probability profiles in time-resolved diffuse reflectance measurement

    NASA Astrophysics Data System (ADS)

    Sawosz, P.; Kacprzak, M.; Weigl, W.; Borowska-Solonynko, A.; Krajewski, P.; Zolek, N.; Ciszek, B.; Maniewski, R.; Liebert, A.

    2012-12-01

    A time-gated intensified CCD camera was applied for time-resolved imaging of light penetrating in an optically turbid medium. Spatial distributions of light penetration probability in the plane perpendicular to the axes of the source and the detector were determined at different source positions. Furthermore, visiting probability profiles of diffuse reflectance measurement were obtained by the convolution of the light penetration distributions recorded at different source positions. Experiments were carried out on homogeneous phantoms, more realistic two-layered tissue phantoms based on the human skull filled with Intralipid-ink solution and on cadavers. It was noted that the photons visiting probability profiles depend strongly on the source-detector separation, the delay between the laser pulse and the photons collection window and the complex tissue composition of the human head.

  10. Integrated experimental setup for angle resolved photoemission spectroscopy of transuranic materials.

    PubMed

    Graham, Kevin S; Joyce, John J; Durakiewicz, Tomasz

    2013-09-01

    We have developed the Angle Resolved Photoemission Spectroscopy (ARPES) system for transuranic materials. The ARPES transuranic system is an endstation upgrade to the Laser Plasma Light Source (LPLS) at Los Alamos National Laboratory. The LPLS is a tunable light source for photoemission with a photon energy range covering the vacuum ultraviolet (VUV) and soft x-ray regions (27-140 eV). The LPLS was designed and developed for transuranic materials. Transuranic photoemission is currently not permitted at the public synchrotrons worldwide in the VUV energy range due to sample encapsulation requirements. With the addition of the ARPES capability to the LPLS system there is an excellent opportunity to explore new details centered on the electronic structure of actinide and transuranic materials.

  11. The influence of physical activity in the progression of experimental lung cancer in mice.

    PubMed

    Paceli, Renato Batista; Cal, Rodrigo Nunes; dos Santos, Carlos Henrique Ferreira; Cordeiro, José Antonio; Neiva, Cassiano Merussi; Nagamine, Kazuo Kawano; Cury, Patrícia Maluf

    2012-07-15

    Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb - C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.

  12. Experimental ventilator-induced lung injury: exacerbation by positive end-expiratory pressure.

    PubMed

    Villar, Jesús; Herrera-Abreu, Maria Teresa; Valladares, Francisco; Muros, Mercedes; Pérez-Méndez, Lina; Flores, Carlos; Kacmarek, Robert M

    2009-06-01

    Previous experimental studies of ventilator-induced lung injury have shown that positive end-expiratory pressure (PEEP) is protective. The authors hypothesized that the application of PEEP during volume-controlled ventilation with a moderately high tidal volume (VT) in previously healthy in vivo rats does not attenuate ventilator-induced lung injury if the peak airway pressure markedly increases during the application of PEEP. Sixty healthy, male Sprague-Dawley rats were anesthetized and randomized to be mechanically ventilated for 4 h at (1) VT of 6 ml/kg, (2) VT of 20 ml/kg, or (3) VT of 20 ml/kg plus 10 cm H2O of PEEP. Peak airway pressures, gas exchange, histologic evaluation, mortality, total lung tissue cytokine gene expression, and serum cytokine concentrations were analyzed. Peak airway pressures exceeded 30 cm H2O with high VT plus PEEP. All lungs ventilated with high VT had perivascular edema and inflammatory infiltrates. In addition, those ventilated with PEEP had small hemorrhages foci. Five animals from the high VT plus PEEP group died (P = 0.020). Animals ventilated with high VT (with or without PEEP) had a substantial increase in serum interleukin-6 (P = 0.0002), and those ventilated with high VT plus PEEP had a 5.5-fold increase in systemic levels of tumor necrosis factor-alpha (P = 0.007). In contrast to previous reports, PEEP exacerbated lung damage and contributed to fatal outcome in an in vivo, mild overdistension model of ventilator-induced lung injury in previously healthy rats. That is, the addition of high PEEP to a constant large VT causes injury in previously healthy animals.

  13. A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.

    PubMed

    Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N

    2015-05-01

    The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  14. A flexible experimental setup for femtosecond time-resolved broad-band ellipsometry and magneto-optics

    SciTech Connect

    Boschini, F.; Hedayat, H.; Piovera, C.; Dallera, C.; Gupta, A.; Carpene, E.

    2015-01-15

    A versatile experimental setup for femtosecond time-resolved ellipsometry and magneto-optical Kerr effect measurements in the visible light range is described. The apparatus is based on the pump-probe technique and combines a broad-band probing beam with an intense near-infrared pump. According to Fresnel scattering matrix formalism, the analysis of the reflected beam at different polarization states of the incident probe light allows one to determine the diagonal and the off-diagonal elements of the dielectric tensor in the investigated sample. Moreover, the pump-probe method permits to study the dynamics of the dielectric response after a short and intense optical excitation. The performance of the experimental apparatus is tested on CrO{sub 2} single crystals as a benchmark.

  15. Theoretical and experimental study of the Suzuki-phase photonic crystal lattice by angle-resolved photoluminescence spectroscopy.

    PubMed

    Alija, Alfonso R; Martínez, Luis J; Postigo, Pablo A; Sánchez-Dehesa, Jose; Galli, Matteo; Politi, Alberto; Patrini, Maddalena; Andreani, Lucio C; Seassal, Christian; Viktorovitch, Pierre

    2007-01-22

    A complete theoretical and experimental analysis of the photonic band structure for the Suzuki-phase lattice is presented. The band diagrams were calculated by two-dimensional plane wave expansion and three-dimensional guided-mode expansion methods. Angle resolved photoluminescence spectroscopy has been used to measure the emission of the photonic crystal structure realized in active InAsP/InP slabs. Photonic bands with a very low group velocity along an entire direction of the reciprocal lattice have been measured, which may have important applications on future photonic devices. The experimentally determined dispersion is in very good agreement with the calculated photonic bands. The presence of defect modes produced by microcavities in the Suzuki-phase lattice has also been established.

  16. Estradiol worsens the syndrome of ischemia-reperfusion injury in an experimental lung transplantation model.

    PubMed

    Santana-Rodríguez, Norberto; Clavo, Bernardino; Llontop, Pedro; López, Ana; García-Castellano, José Manuel; Machín, Rubén P; Ponce, Miguel A; Fiuza, María D; García-Herrera, Ricardo; Brito, Yanira; Yordi, Nagib Atallah; Chirino, Ricardo

    2011-06-01

    Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.

  17. Effects of experimental asthma on inflammation and lung mechanics in sickle cell mice.

    PubMed

    Pritchard, Kirkwood A; Feroah, Thom R; Nandedkar, Sandhya D; Holzhauer, Sandra L; Hutchins, William; Schulte, Marie L; Strunk, Robert C; Debaun, Michael R; Hillery, Cheryl A

    2012-03-01

    Experimental asthma increases eosinophil and collagen deposition in the lungs of sickle cell disease (SCD) mice to a greater extent than in control mice. However, the effects of asthma on inflammation and airway physiology remain unclear. To determine effects of asthma on pulmonary inflammation and airway mechanics in SCD mice, hematopoietic stem cell transplantation was used to generate chimeric SCD and hemoglobin A mice. Experimental asthma was induced by sensitizing mice with ovalbumin (OVA). Airway mechanics were assessed using forced oscillation techniques. Mouse lungs were examined histologically and physiologically. Cytokine, chemokine, and growth factors in bronchoalveolar lavage fluid were determined by multiplex. IgE was quantified by ELISA. LDH was quantified using a colorimetric enzymatic assay. At baseline (nonsensitized), chimeric SCD mice developed hemolytic anemia with sickled red blood cells, mild leukocytosis, and increased vascular endothelial growth factor and IL-13 compared with chimeric hemoglobin A mice. Experimental asthma increased perialveolar eosinophils, plasma IgE, and bronchoalveolar lavage fluid IL-1β, IL-4, IL-6, and monocyte chemotactic protein 1 in chimeric hemoglobin A and SCD mice. IFN-γ levels were reduced in both groups. IL-5 was preferentially increased in chimeric SCD mice but not in hemoglobin A mice. Positive end-expiratory pressures and methacholine studies revealed that chimeric SCD mice had greater resistance in large and small airways compared with hemoglobin A mice at baseline and after OVA sensitization. SCD alone induces a baseline lung pathology that increases large and small airway resistance and primes the lungs to increased inflammation and airway hyperresponsiveness after OVA sensitization.

  18. Effects of Experimental Asthma on Inflammation and Lung Mechanics in Sickle Cell Mice

    PubMed Central

    Feroah, Thom R.; Nandedkar, Sandhya D.; Holzhauer, Sandra L.; Hutchins, William; Schulte, Marie L.; Strunk, Robert C.; DeBaun, Michael R.; Hillery, Cheryl A.

    2012-01-01

    Experimental asthma increases eosinophil and collagen deposition in the lungs of sickle cell disease (SCD) mice to a greater extent than in control mice. However, the effects of asthma on inflammation and airway physiology remain unclear. To determine effects of asthma on pulmonary inflammation and airway mechanics in SCD mice, hematopoietic stem cell transplantation was used to generate chimeric SCD and hemoglobin A mice. Experimental asthma was induced by sensitizing mice with ovalbumin (OVA). Airway mechanics were assessed using forced oscillation techniques. Mouse lungs were examined histologically and physiologically. Cytokine, chemokine, and growth factors in bronchoalveolar lavage fluid were determined by multiplex. IgE was quantified by ELISA. LDH was quantified using a colorimetric enzymatic assay. At baseline (nonsensitized), chimeric SCD mice developed hemolytic anemia with sickled red blood cells, mild leukocytosis, and increased vascular endothelial growth factor and IL-13 compared with chimeric hemoglobin A mice. Experimental asthma increased perialveolar eosinophils, plasma IgE, and bronchoalveolar lavage fluid IL-1β, IL-4, IL-6, and monocyte chemotactic protein 1 in chimeric hemoglobin A and SCD mice. IFN-γ levels were reduced in both groups. IL-5 was preferentially increased in chimeric SCD mice but not in hemoglobin A mice. Positive end-expiratory pressures and methacholine studies revealed that chimeric SCD mice had greater resistance in large and small airways compared with hemoglobin A mice at baseline and after OVA sensitization. SCD alone induces a baseline lung pathology that increases large and small airway resistance and primes the lungs to increased inflammation and airway hyperresponsiveness after OVA sensitization. PMID:22033263

  19. Research in the Luquillo Experimental Forest has advanced understanding of tropical forests and resolved management issues

    Treesearch

    A.E. Lugo; T. Heartsill Scalley

    2014-01-01

    Long-term research on the response of wet forests in the Luquillo Experimental Forest (LEF) to natural and anthropogenic disturbances yielded information useful for the management of these forests and to a better understanding of the functioning of tropical forests and how species composition changes under different distrubance regimes. We summarize studies on basal...

  20. Experimental Research and the Managerial Attitude: A Tension to Be Resolved?

    ERIC Educational Resources Information Center

    Benninghoff, Martin; Sormani, Philippe

    2008-01-01

    This article analyses some typical consequences of a specific research policy on experimental research in biology. The policy is conducted by a national funding agency--the Swiss National Science Foundation--through a particular programme, the "National Centres of Competence in Research" which is designed to promote both "scientific…

  1. Experimental Research and the Managerial Attitude: A Tension to Be Resolved?

    ERIC Educational Resources Information Center

    Benninghoff, Martin; Sormani, Philippe

    2008-01-01

    This article analyses some typical consequences of a specific research policy on experimental research in biology. The policy is conducted by a national funding agency--the Swiss National Science Foundation--through a particular programme, the "National Centres of Competence in Research" which is designed to promote both "scientific…

  2. Experimental observation of spatially resolved photo-luminescence intensity distribution in dual mode upconverting nanorod bundles

    NASA Astrophysics Data System (ADS)

    Kumar, Pawan; Singh, Satbir; Singh, V. N.; Singh, Nidhi; Gupta, R. K.; Gupta, Bipin Kumar

    2017-02-01

    A novel method for demonstration of photoluminescence intensity distribution in upconverting nanorod bundles using confocal microscopy is reported. Herein, a strategy for the synthesis of highly luminescent dual mode upconverting/downshift Y1.94O3:Ho3+0.02/Yb3+0.04 nanorod bundles by a facile hydrothermal route has been introduced. These luminescent nanorod bundles exhibit strong green emission at 549 nm upon excitations at 449 nm and 980 nm with quantum efficiencies of ~6.3% and ~1.1%, respectively. The TEM/HRTEM results confirm that these bundles are composed of several individual nanorods with diameter of ~100 nm and length in the range of 1–3 μm. Furthermore, two dimensional spatially resolved photoluminescence intensity distribution study has been carried out using confocal photoluminescence microscope throughout the nanorod bundles. This study provides a new direction for the potential use of such emerging dual mode nanorod bundles as photon sources for next generation flat panel optical display devices, bio-medical applications, luminescent security ink and enhanced energy harvesting in photovoltaic applications.

  3. Experimental observation of spatially resolved photo-luminescence intensity distribution in dual mode upconverting nanorod bundles

    PubMed Central

    Kumar, Pawan; Singh, Satbir; Singh, V. N.; Singh, Nidhi; Gupta, R. K.; Gupta, Bipin Kumar

    2017-01-01

    A novel method for demonstration of photoluminescence intensity distribution in upconverting nanorod bundles using confocal microscopy is reported. Herein, a strategy for the synthesis of highly luminescent dual mode upconverting/downshift Y1.94O3:Ho3+0.02/Yb3+0.04 nanorod bundles by a facile hydrothermal route has been introduced. These luminescent nanorod bundles exhibit strong green emission at 549 nm upon excitations at 449 nm and 980 nm with quantum efficiencies of ~6.3% and ~1.1%, respectively. The TEM/HRTEM results confirm that these bundles are composed of several individual nanorods with diameter of ~100 nm and length in the range of 1–3 μm. Furthermore, two dimensional spatially resolved photoluminescence intensity distribution study has been carried out using confocal photoluminescence microscope throughout the nanorod bundles. This study provides a new direction for the potential use of such emerging dual mode nanorod bundles as photon sources for next generation flat panel optical display devices, bio-medical applications, luminescent security ink and enhanced energy harvesting in photovoltaic applications. PMID:28211891

  4. Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury.

    PubMed

    Liu, Yong; Zhou, Dan; Long, Fei-Wu; Chen, Ke-Ling; Yang, Hong-Wei; Lv, Zhao-Yin; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

    2016-03-01

    Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-κB activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-α, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-κB activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-κB activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.

  5. Dynamic computed tomography: a novel technique to study lung aeration and atelectasis formation during experimental CPR.

    PubMed

    Markstaller, Klaus; Karmrodt, Jens; Doebrich, Marcus; Wolcke, Benno; Gervais, Hendrik; Weiler, Norbert; Thelen, Manfred; Dick, Wolfgang; Kauczor, Hans-Ulrich; Eberle, Balthasar

    2002-06-01

    To develop an image based technique to study the effect of different ventilatory strategies on lung ventilation and alveolar recruitment during cardiopulmonary resuscitation (CPR). (1) Technical development of the following components: (a) construction of an external chest compression device, which does not interfere with CT imaging, and (b) development of a software tool to detect lung parenchyma automatically and to calculate radiological density parameters. (2) Feasibility studies: three strategies of CPR ventilation were performed and imaged in one animal each (pigs, 25 kg): volume-constant ventilation (VCV), no ventilation, or continuous airway pressure (CPAP). One minute after induction of circulatory arrest inside the CT scanner, external chest compressions started at a rate of 100 cpm, and one of the ventilation modes was initiated. After 1 min, intravenous epinephrine was added as a bolus (40 microg/kg), followed by a continuous infusion (13 microg/kg per min). Six minutes later, dynamic CT acquisitions (temporal resolution: 100 ms) commenced. Simultaneously, arterial blood gases, acid base status and haemodynamics were sampled. Using a modified chest compression device, dynamic CT acquisitions are feasible during closed-chest CPR. In three pilot experiments with different ventilation strategies, the dedicated software tool allowed to quantify ventilated, atelectatic and over-distended fractions of total lung area. VCV showed a large amount of atelectasis, which was recruited during every respiratory cycle. No ventilation led to atelectasis to govern over 50% of the total lung area. CPAP caused less atelectasis as VCV, and no cyclic recruitment and de-recruitment phenomena were observed. We demonstrate a novel experimental set up, which allows quantification of different lung compartments during ongoing CPR and may become useful in comparing the direct pulmonary effects of different ventilatory strategies in the settings of Basic and Advanced Cardiac Life

  6. Resolving apparent conflicts between theoretical and experimental models of phosphate monoester hydrolysis.

    PubMed

    Duarte, Fernanda; Åqvist, Johan; Williams, Nicholas H; Kamerlin, Shina C L

    2015-01-28

    Understanding phosphoryl and sulfuryl transfer is central to many biochemical processes. However, despite decades of experimental and computational studies, a consensus concerning the precise mechanistic details of these reactions has yet to be reached. In this work we perform a detailed comparative theoretical study of the hydrolysis of p-nitrophenyl phosphate, methyl phosphate and p-nitrophenyl sulfate, all of which have served as key model systems for understanding phosphoryl and sulfuryl transfer reactions, respectively. We demonstrate the existence of energetically similar but mechanistically distinct possibilities for phosphate monoester hydrolysis. The calculated kinetic isotope effects for p-nitrophenyl phosphate provide a means to discriminate between substrate- and solvent-assisted pathways of phosphate monoester hydrolysis, and show that the solvent-assisted pathway dominates in solution. This preferred mechanism for p-nitrophenyl phosphate hydrolysis is difficult to find computationally due to the limitations of compressing multiple bonding changes onto a 2-dimensional energy surface. This problem is compounded by the need to include implicit solvation to at least microsolvate the system and stabilize the highly charged species. In contrast, methyl phosphate hydrolysis shows a preference for a substrate-assisted mechanism. For p-nitrophenyl sulfate hydrolysis there is only one viable reaction pathway, which is similar to the solvent-assisted pathway for phosphate hydrolysis, and the substrate-assisted pathway is not accessible. Overall, our results provide a unifying mechanistic framework that is consistent with the experimentally measured kinetic isotope effects and reconciles the discrepancies between theoretical and experimental models for these biochemically ubiquitous classes of reaction.

  7. The Complete, Temperature Resolved Experimental Spectrum of Methanol Between 560 and 654 GHZ

    NASA Astrophysics Data System (ADS)

    Fortman, Sarah M.; Neese, Christopher F.; De Lucia, Frank C.

    2013-06-01

    The complete spectrum of methanol (CH_3OH) in the 560.4-654.0 GHz spectral region has been characterized over a range of astrophysically significant temperatures, 248-397 K. Analysis of experimental spectra recorded with absolute intensity calibration over a slow temperature ramp provides a means for the simulation of the spectrum as a function of temperature without a complete quantum mechanical (QM) model. These results include contributions from v_t = 3 and other higher states that are difficult to model via QM techniques. They also contain contributions from the ^{13}C isotopologue in natural abundance. These results are used to both provide catalogs in the usual line frequency, linestrength, and lower state energy format and in a frequency point-by-point format that is particularly well suited for the characterization of blended lines. In contrast to our earlier work on the semi-rigid species ethyl cyanide and vinyl cyanide, significant intensity difference between these experimental values and those calculated by QM methods were found for some of the lines. Analysis of these differences points to the difficulty of the calculation of dipole matrix elements in the context of the internal rotation of the methanol molecule. We will compare our experimental intensities with the most recent QM model, as well as an earlier QM model that includes the variation of the dipole moment function with the torsional angle. S. M. Fortman, I. R. Medvedev, C. F. Neese, and F. C. De Lucia, Astrophys. J. 737, 20/1-6 (2011). L.-H. Xu, et al. J. Mol. Spectrosc. 251, 305-313 (2008). M. A. Mekhtiev, P. D. Godfrey, and J. T. Hougen, J. Mol. Spectrosc. 194, 171-178 (1999).

  8. Resolving Apparent Conflicts between Theoretical and Experimental Models of Phosphate Monoester Hydrolysis

    PubMed Central

    2014-01-01

    Understanding phosphoryl and sulfuryl transfer is central to many biochemical processes. However, despite decades of experimental and computational studies, a consensus concerning the precise mechanistic details of these reactions has yet to be reached. In this work we perform a detailed comparative theoretical study of the hydrolysis of p-nitrophenyl phosphate, methyl phosphate and p-nitrophenyl sulfate, all of which have served as key model systems for understanding phosphoryl and sulfuryl transfer reactions, respectively. We demonstrate the existence of energetically similar but mechanistically distinct possibilities for phosphate monoester hydrolysis. The calculated kinetic isotope effects for p-nitrophenyl phosphate provide a means to discriminate between substrate- and solvent-assisted pathways of phosphate monoester hydrolysis, and show that the solvent-assisted pathway dominates in solution. This preferred mechanism for p-nitrophenyl phosphate hydrolysis is difficult to find computationally due to the limitations of compressing multiple bonding changes onto a 2-dimensional energy surface. This problem is compounded by the need to include implicit solvation to at least microsolvate the system and stabilize the highly charged species. In contrast, methyl phosphate hydrolysis shows a preference for a substrate-assisted mechanism. For p-nitrophenyl sulfate hydrolysis there is only one viable reaction pathway, which is similar to the solvent-assisted pathway for phosphate hydrolysis, and the substrate-assisted pathway is not accessible. Overall, our results provide a unifying mechanistic framework that is consistent with the experimentally measured kinetic isotope effects and reconciles the discrepancies between theoretical and experimental models for these biochemically ubiquitous classes of reaction. PMID:25423607

  9. Resolving solvophobic interactions inferred from experimental solvation free energies and evaluated from molecular simulations

    NASA Astrophysics Data System (ADS)

    Barnett, J. Wesley; Bhutta, Amna; Bierbrier, Sarah C.; da Silva Moura, Natalia; Ashbaugh, Henry S.

    2017-01-01

    Ben-Naim estimated the solvent-mediated interaction between methanes based on experimental solvation free energy differences between chemically similar hydrocarbons. Interactions were predicted to be strongest in water, dominated by characteristic entropic gains. We use molecular simulations in combination with an empirical interpolation procedure that bridges interactions from outside methane's excluded volume down to overlap to test Ben-Naim's estimates. While Ben-Naim's approach captures many distinctive trends, the alchemical differences between methane and a methyl unit play a non-trivial role on the predicted association strength and the sign of enthalpic and entropic components of the interaction free energy in water and ethanol.

  10. Locally resolved characterization of progressive addition lenses by calculation of the modulation transfer function using experimental ray tracing

    NASA Astrophysics Data System (ADS)

    Gutierrez, Gustavo; Hilbig, David; Fleischmann, Friedrich; Henning, Thomas

    2017-02-01

    Due to the exotic freeform surface exhibited by Progressive Addition Lenses, a new characterization approach that takes into account the projection of the eye pupil over the lens is required. In this work, a locally resolved description of the performance of the lens has been obtained by calculating the Modulation Transfer Function (MTF) for uniformly spaced subaperture positions. This quality metric is conveniently suitable to characterize imaging systems, because it describes the contrast resolving capabilities of the lens as a function of the spatial frequency. In addition, it is independent of the eye perception of the test engineer. The MTF has been indirectly calculated using Experimental Ray Tracing, by extracting the values of the ray slopes of each subaperture from the complete ray traced data. By following this procedure, two-dimensional maps are generated using two different criteria. The first criterion is based on the determination of the normalized spatial frequency where the MTF has declined by 50 %. The second one uses a simplified Strehl ratio. Also, the results for different subaperture diameters are obtained without the need for changing the setup or repeating the measurements.

  11. Resolving small signal measurements in experimental plasma environments using calibrated subtraction of noise signals

    SciTech Connect

    Fimognari, P. J. Demers, D. R.; Chen, X.; Schoch, P. M.

    2014-11-15

    The performance of many diagnostic and control systems within fusion and other fields of research are often detrimentally affected by spurious noise signals. This is particularly true for those (such as radiation or particle detectors) working with very small signals. Common sources of radiated and conducted noise in experimental fusion environments include the plasma itself and instrumentation. The noise complicates data analysis, as illustrated by noise on signals measured with the heavy ion beam probe (HIBP) installed on the Madison Symmetric Torus. The noise is time-varying and often exceeds the secondary ion beam current (in contrast with previous applications). Analysis of the noise identifies the dominant source as photoelectric emission from the detectors induced by ultraviolet light from the plasma. This has led to the development of a calibrated subtraction technique, which largely removes the undesired temporal noise signals from data. The advantages of the technique for small signal measurement applications are demonstrated through improvements realized on HIBP fluctuation measurements.

  12. Comparison of calculated and experimentally resolved rate constants for excitation energy transfer in C-phycocyanin. 2. Trimers

    SciTech Connect

    Debreczeny, M.F.; Sauer, K.; Zhou, J.; Bryant, D.A.

    1995-05-18

    Resolution of the absorption spectrum of the {beta}{sub 155} chromophore in C-phycocyanin (PC) trimers is achieved by comparison of the steady state absorption spectra of ({alpha}{sup PC}{beta}{sup PC}){sub 3} and ({alpha}{sup PC}{beta}{sup *}){sub 3}. Comparison of the anisotropy decays of ({alpha}{sup PC}{beta}{sup PC}){sub 3} and ({alpha}{sup PC}{beta}{sup *}){sub 3} also greatly aids in the assignment of the dominant kinetic processes in PC trimers. A comparison is made of calculated Foerster rate constants for energy transfer with those rate constants resolved experimentally in the PC trimers. 35 refs.., 10 figs., 2 tabs.

  13. Experimental lung injury promotes alterations in energy metabolism and respiratory mechanics in the lungs of rats: prevention by exercise.

    PubMed

    da Cunha, Maira J; da Cunha, Aline A; Scherer, Emilene B S; Machado, Fernanda Rossato; Loureiro, Samanta O; Jaenisch, Rodrigo B; Guma, Fátima; Lago, Pedro Dal; Wyse, Angela T S

    2014-04-01

    In the present study we investigated the effects of lung injury on energy metabolism (succinate dehydrogenase, complex II, cytochrome c oxidase, and ATP levels), respiratory mechanics (dynamic and static compliance, elastance and respiratory system resistance) in the lungs of rats, as well as on phospholipids in bronchoalveolar lavage fluid. The protective effect of physical exercise on the alterations caused by lung injury, including lung edema was also evaluated. Wistar rats were submitted to 2 months of physical exercise. After this period the lung injury was induced by intratracheal instillation of lipopolysaccharide. Adult Wistar rats were submitted to 2 months of physical exercise and after this period the lung injury was induced by intratracheal instillation of lipopolysaccharide in dose 100 μg/100 g body weight. The sham group received isotonic saline instillation. Twelve hours after the injury was performed the respiratory mechanical and after the rats were decapitated and samples were collected. The rats subjected to lung injury presented a decrease in activities of the enzymes of the electron transport chain and ATP levels in lung, as well as the formation of pulmonary edema. A decreased lung dynamic and static compliance, as well as an increase in respiratory system resistance, and a decrease in phospholipids content were observed. Physical exercise was able to totally prevent the decrease in succinate dehydrogenase and complex II activities and the formation of pulmonary edema. It also partially prevented the increase in respiratory system resistance, but did not prevent the decrease in dynamic and static compliance, as well as in phospholipids content. These findings suggest that the mitochondrial dysfunction may be one of the important contributors to lung damage and that physical exercise may be beneficial in this pathology, although it did not prevent all changes present in lung injury.

  14. Experimental setup for temporally and spatially resolved ICCD imaging of (sub)nanosecond streamer plasma

    NASA Astrophysics Data System (ADS)

    Huiskamp, T.; Sengers, W.; Pemen, A. J. M.

    2016-12-01

    Streamer discharges are efficient non-thermal plasmas for air purification and can be generated in wire-cylinder electrode structures (the plasma reactor). When (sub)nanosecond high-voltage pulses are used to generate the plasma, components like a plasma reactor behave as transmission lines, where transmission times and reflections become important. We want to visually study the influence of these transmission-line effects on the streamer development in the reactor. Therefore, we need a unique experimental setup, which allows us to image the streamers with nanosecond time resolution over the entire length of the plasma reactor. This paper describes the setup we developed for this purpose. The setup consists of a large frame in which a specially designed plasma reactor can be mounted and imaged from below by an intensified charge-coupled device (ICCD) camera. This camera is mounted on a platform which can be moved by a stepper motor. A computer automates all the experiments and controls the camera movement, camera settings, and the nanosecond high-voltage pulse source we use for the experiments. With the automated setup, we can make ICCD images of the entire plasma reactor at different instances of time with nanosecond resolution (with a jitter of less than several hundreds of picoseconds). Consequently, parameters such as the streamer length and width can be calculated automatically.

  15. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust.

    PubMed

    Rudell, B; Ledin, M C; Hammarström, U; Stjernberg, N; Lundbäck, B; Sandström, T

    1996-10-01

    Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap.

  16. Pulsatility flow around a single cylinder - an experimental model of flow inside an artificial lung

    NASA Astrophysics Data System (ADS)

    Lin, Yu-Chun; Bull, Joseph L.

    2004-11-01

    Pulsatile flow past a single cylinder is experimentally investigated using particle image velocimetry. This study aims to elucidate the effects of pulstility on the velocity field, which influences the convection-dominated transport within the fluid. The artificial lung device can be connected in parallel or series with the native lungs and may potentially be used as a bridge to transplant or for pulmonary replacement. The artificial lung consists of hollow microfibers through which gas flows and blood flows around. Blood flow through the device is pulsatile because it is driven entirely by the right heart. Steady flow over bluff bodies has been investigated in many contexts, such as heat exchangers. However, few studies have been investigated the effect of pulsatility. The effects of frequency, amplitude of pulsatility, and average flow rate on the formation of vortices after a cylinder are examined. Vortices near the cylinder are found to develop at lower Reynolds number in pulsatile flow than in steady flow. This work is supported by NIH grant R01 HL69420-01.

  17. Nonhematopoietic NADPH oxidase regulation of lung eosinophilia and airway hyperresponsiveness in experimentally induced asthma

    PubMed Central

    Abdala-Valencia, Hiam; Earwood, Julie; Bansal, Shelly; Jansen, Michael; Babcock, George; Garvy, Beth; Wills-Karp, Marsha; Cook-Mills, Joan M.

    2009-01-01

    Pulmonary eosinophilia is one of the most consistent hallmarks of asthma. Infiltration of eosinophils into the lung in experimental asthma is dependent on the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Ligation of VCAM-1 activates endothelial cell NADPH oxidase, which is required for VCAM-1-dependent leukocyte migration in vitro. To examine whether endothelial-derived NADPH oxidase modulates eosinophil recruitment in vivo, mice deficient in NADPH oxidase (CYBB mice) were irradiated and received wild-type hematopoietic cells to generate chimeric CYBB mice. In response to ovalbumin (OVA) challenge, the chimeric CYBB mice had increased numbers of eosinophils bound to the endothelium as well as reduced eosinophilia in the lung tissue and bronchoalveolar lavage. This occurred independent of changes in VCAM-1 expression, cytokine/chemokine levels (IL-5, IL-10, IL-13, IFNγ, or eotaxin), or numbers of T cells, neutrophils, or mononuclear cells in the lavage fluids or lung tissue of OVA-challenged mice. Importantly, the OVA-challenged chimeric CYBB mice had reduced airway hyperresponsiveness (AHR). The AHR in OVA-challenged chimeric CYBB mice was restored by bypassing the endothelium with intratracheal administration of eosinophils. These data suggest that VCAM-1 induction of NADPH oxidase in the endothelium is necessary for the eosinophil recruitment during allergic inflammation. Moreover, these studies provide a basis for targeting VCAM-1-dependent signaling pathways in asthma therapies. PMID:17293377

  18. [The results of experimental study of six-hour heart-lung preservation by autoperfusion method--its evaluation of optimal conditions and lung function after preservation].

    PubMed

    Matsuoka, M; Makino, S; Hattori, R; Imura, M; Higashi, K; Morimoto, T; Yada, I; Namikawa, S; Yuasa, H; Kusagawa, M

    1989-04-01

    Up to date, it has been reported that the maintenance of ideal function of the preserved lungs were much more difficult than that of the hearts in heart-lung preservation. In this communication the authors have reported the results of experimental study for optimal conditions for preserving better function of the lungs by autoperfusion method by means of heart-lung preparation using 43 dogs. In this study the conditions of the preservation were fixed as following: perfusing blood temperature 29 degrees C, blood flow 30 ml/kg/min., FiO2 30%, FiCO2 5%, tidal volume 15 ml/kg, ventilation rate 10/min., and PEEP 5 cmH2O. Glucose-Insulin-Potassium (0.03 gm., 0.05 U., 0.02 mEq/kg/hr. respectively) were administered continuously by an infusion pump. The results showed that extravascular lung water contents after 6 hours of preservation was 0.79 (mean) +/- 0.01 (SD), which was increased only 1% over than the control group: 0.78 +/- 0.01. There was no significant difference of static lung compliance in two groups: the preserved group was 0.47 +/- 0.02 ml/gm.cmH2O compared to 0.51 +/- 0.06 in the control group. These results suggest that the autoperfusion method on our preserving conditions seems to be very promising and very effective to keep much better condition of the lungs in heart-lung preservation.

  19. Effects of exogenous surfactant on the non-heart-beating donor lung graft in experimental lung transplantation – a stereological study

    PubMed Central

    Herrmann, Gudrun; Knudsen, Lars; Madershahian, Navid; Mühlfeld, Christian; Frank, Konrad; Rahmanian, Parwis; Wahlers, Thorsten; Wittwer, Thorsten; Ochs, Matthias

    2014-01-01

    The use of non-heart-beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non-SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design-based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham-operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non-SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron-chovascular connective tissue. Regarding intra-alveolar oedema, no statistically significant difference could be found between SF and non-SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart-beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed

  20. Effect of partial liquid ventilation and nebulized perfluorocarbon on CT lung density distribution: randomized controlled study of experimental lung injury.

    PubMed

    Kelly, K P; Stenson, B J; Drummond, G B

    2005-05-01

    Perfluorocarbon (PFC) liquid can improve gas exchange in acute lung injury. How PFC aerosol is distributed in the lung is unknown. We induced lung injury in rabbits with saline lavage, followed by mechanical ventilation in the supine position. The animals were divided into three groups: a control group, a group treated with partial liquid ventilation and a group given nebulized perfluorocarbon (PF 5080). We made CT image slices of the excised lungs. In the apical, middle and caudal slices we defined three regions of interest, from anterior to posterior, and noted the mean attenuation of each area. We also studied two rabbits which had not received lung injury or mechanical ventilation. Group means were different between the normal rabbits and all three study groups. There was a difference between the control and partial liquid ventilation groups, and between the partial liquid ventilation and nebulized groups, but no difference between the nebulized and control groups. Within each treatment group, there was no regional difference in the distribution of density. PF 5080 is not deposited in large amounts by aerosol. Less PFC was found in the lungs after partial liquid ventilation than expected. Within treatment groups, lung densities indicate less gravitational and regional differences than found in other studies.

  1. Involvement of exosomes in lung inflammation associated with experimental acute pancreatitis.

    PubMed

    Bonjoch, Laia; Casas, Vanessa; Carrascal, Montserrat; Closa, Daniel

    2016-10-01

    A frequent complication of acute pancreatitis is the lung damage associated with the systemic inflammatory response. Although various pro-inflammatory mediators generated at both local and systemic levels have been identified, the pathogenic mechanisms of the disease are still poorly understood. In recent years, exosomes have emerged as a new intercellular communication system able to transfer encapsulated proteins and small RNAs and protect them from degradation. Using an experimental model of taurocholate-induced acute pancreatitis in rats, we aimed to evaluate the role of exosomes in the extent of the systemic inflammatory response. Induction of pancreatitis increased the concentration of circulating exosomes, which showed a different proteomic profile to those obtained from control animals. A series of tracking experiments using PKH26-stained exosomes revealed that circulating exosomes effectively reached the alveolar compartment and were internalized by macrophages. In vitro experiments revealed that exosomes obtained under inflammatory conditions activate and polarize these alveolar macrophages towards a pro-inflammatory phenotype. Interestingly, the proteomic analysis of circulating exosomes during acute pancreatitis suggested a multi-organ origin with a relevant role for the liver as a source of these vesicles. Tracking experiments also revealed that the liver retains the majority of exosomes from the peritoneal cavity. We conclude that exosomes are involved in the lung damage associated with experimental acute pancreatitis and could be relevant mediators in the systemic effects of pancreatitis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. Experimental measurements of lung resonant frequencies in a bottlenose dolphin (Tursiops truncatus) and white whale (Delphinapterus leucas)

    NASA Astrophysics Data System (ADS)

    Finneran, James J.

    2003-04-01

    An acoustic backscatter technique was used to estimate in vivo whole-lung resonant frequencies in a bottlenose dolphin (Tursiops truncatus) and a white whale (Delphinapterus leucas). Subjects were trained to submerge and position themselves near an underwater sound projector and a receiving hydrophone. Acoustic pressure measurements were made near the subjects' lungs while insonified with pure tones at frequencies from 16 to 100 Hz. Whole-lung resonant frequencies were estimated by comparing pressures measured near the subjects' lungs to those measured from the same location without the subject present. Experimentally measured resonant frequencies and damping ratios were much higher than those predicted using equivalent volume spherical air bubble models. The experimental technique, data analysis method, and discrepancy between the observed and predicted values will be discussed. The potential effects of depth on the resonance frequencies will also be discussed.

  3. New insights into experimental evidence on atelectasis and causes of lung injury.

    PubMed

    Muders, Thomas; Wrigge, Hermann

    2010-06-01

    Development of atelectasis is common in both patients with and without lung injury during mechanical ventilation. Atelectasis might contribute to or attenuate lung injury by different possible mechanisms. Possible direct effects of atelectasis include inflammatory activation or infection of the affected regional lung tissues. In addition, the loss of aerated lung volume due to atelectasis in mechanically ventilated patients indirectly results in increased mechanical strain of the reduced number of ventilated lung regions, if ventilation is not adequately decreased. This study discusses possible mechanisms and interactions between atelectasis formation in the lungs and the development or aggravation of acute lung injury.

  4. Experimental Approach to Visualize Flow in a Stacked Hollow Fiber Bundle of an Artificial Lung With Particle Image Velocimetry.

    PubMed

    Kaesler, Andreas; Schlanstein, Peter C; Hesselmann, Felix; Büsen, Martin; Klaas, Michael; Roggenkamp, Dorothee; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Arens, Jutta

    2017-06-01

    Flow distribution is key in artificial lungs, as it directly influences gas exchange performance as well as clot forming and blood damaging potential. The current state of computational fluid dynamics (CFD) in artificial lungs can only give insight on a macroscopic level due to model simplification applied to the fiber bundle. Based on our recent work on wound fiber bundles, we applied particle image velocimetry (PIV) to the model of an artificial lung prototype intended for neonatal use to visualize flow distribution in a stacked fiber bundle configuration to (i) evaluate the feasibility of PIV for artificial lungs, (ii) validate CFD in the fiber bundle of artificial lungs, and (iii) give a suggestion how to incorporate microscopic aspects into mainly macroscopic CFD studies. To this end, we built a fully transparent model of an artificial lung prototype. To increase spatial resolution, we scaled up the model by a factor of 5.8 compared with the original size. Similitude theory was applied to ensure comparability of the flow distribution between the device of original size and the scaled-up model. We focused our flow investigation on an area (20 × 70 × 43 mm) in a corner of the model with a Stereo-PIV setup. PIV data was compared to CFD data of the original sized artificial lung. From experimental PIV data, we were able to show local flow acceleration and declaration in the fiber bundle and meandering flow around individual fibers, which is not possible using state-of-the-art macroscopic CFD simulations. Our findings are applicable to clinically used artificial lungs with a similar stacked fiber arrangement (e.g., Novalung iLa and Maquet QUADROX-I). With respect to some limitations, we found PIV to be a feasible experimental flow visualization technique to investigate blood-sided flow in the stacked fiber arrangement of artificial lungs. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  5. Changes of myocardial capillary density in progression of experimental lung emphysema.

    PubMed

    Sulkowski, S; Musiatowicz, B; Sulkowska, M; Sobaniec-Lotowska, M; Dziechiol, J; Sulik, M; Szynaka, B

    1996-01-01

    A morphometrical analysis of changes in the heart of rats with experimental lung emphysema due to single intratracheal administration of papain solution has been done. Special attention has been paid to quantitative changes of capillaries and to the cardiomyocyte diameter in respective regions of the myocardium after one, three and six months following the administration of papain. A histological and morphometrical analysis of changes in the lungs has also been carried out and partial pressures of oxygen and carbon dioxide in the arterial blood of the examined animals have been marked. It has been found that a single administration of papain caused emphysematous changes in the lungs, growing more intense until the third month of the experiment. The progression of these changes corresponded to a capillary density increase in the right ventricle, interventricular septum and in the subendocardial layer of the left ventricle. The increase in the number of capillaries was interpreted as the first adaptive stage of cor pulmonale development and explained by the occurrence of angiogenesis. The changes co-existed with a decrease in partial pressure of oxygen in the arterial blood. After six months of the experiment, a reduction in capillary density in the heart regions mentioned above and a simultaneous increase in the cardiomycyte transversal diameter were observed, being the exponents of evident myocardial hypertrophy. Development of ultrastructural changes in the hearts of rats has been analysed too. Simultaneous development of changes in the right ventricle muscle and in the subendocardial layer of the heart left ventricle myocardium was observed. The role of hypoxia as a one of essential factors responsible for the observed morphologic changes has been discussed.

  6. SU-E-T-178: Experimental Study of Acceptable Movement Conditions for SBRT Lung Treatments

    SciTech Connect

    Carrasco de Fez, P; Ruiz-Martinez, A; Jornet, N; Eudaldo, T; Latorre-Musoll, A; Ribas, Morales M

    2014-06-01

    Purpose: To experimentally study the acceptable movement conditions for SBRT lung treatments we quantified with film dosimetry the change in dose distributions due to periodic movements of 5 different amplitudes and 4 respiratory gating duty cycles on a SBRT treatment plan. Methods: We planned a SBRT treatment plan for the QUASAR™ (Modus Medical) phantom equipped with the respiratory motion device. We placed a 3 mm water-equivalent sphere simulating a tumour inside the lung-equivalent insert. This sphere is divided in two hemispheres that allow placing films in between. We used radiochromic EBT2™ (Ashland) films. We oriented the lung insert in such a way that sagittal dose distributions could be measured. We applied a sinusoidal movement with 3 s period for 5 different amplitudes of 0(static), 5, 7, 10, 15 and 20 mm without gating. For the 20 mm amplitude we studied the gating technique with 4 duty cycles of 20, 40, 60 and 80% of the respiratory cycle. Each situation was irradiated in a Clinac 2100 linac (Varian) equipped with the RPM™ system. FilmQA Pro™ (Ashland) software together with an Expression 10000XL scanner (EPSON) were used to analyze and compare the measured dose distributions with those planned by the Eclipse™ TPS v. 8.9 (Varian) by means of gamma analysis with 6 criteria: 5%/3mm, 5%/2mm, 5%/1mm, 3%/3mm, 3%/2mm and 2%/2mm (threshold of 10%). Results: Movements with amplitude of less than 7mm do not significantly modified the dosimetry. Gating duty cycles of less than 40% yielded also acceptable results for a 2 cm amplitude movement. Conclusion: To safely perform daily accurate SBRT treatments, movements have to be restricted to 7 mm amplitude (±3.5 mm). Otherwise, a gating strategy should be considered.

  7. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust.

    PubMed Central

    Rudell, B; Ledin, M C; Hammarström, U; Stjernberg, N; Lundbäck, B; Sandström, T

    1996-01-01

    OBJECTIVES: Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. METHODS: Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. RESULTS: The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. CONCLUSION: Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap. PMID:8943829

  8. The effect of activated alveolar macrophages on experimental lung emphysema development. III. Morphological analysis of the lung tissue and alveolar macrophages in situ.

    PubMed

    Sulkowski, S; Nowak, H F; Sulkowska, M; Sobaniec-Lotowska, M; Andrzejewska, A; Sulik, M; Dziecioł, J; Famulski, W; Poczopko, B

    1995-01-01

    Morphological (in light and transmission electron microscope) as well as morphometrical analysis of the lungs was performed on experimental, papain-induced lung emphysema. Development of emphysematous changes was studied seven days after a single intratracheal instillation of papain solution. The effect of alveolar macrophages (AM) activation by BCG-vaccine on changes in pulmonary tissue was analyzed. In the rats given BCG the number of AM increased and demonstrated enhanced activity. Increase in reticulin fibre density in places of AM cumulation, particularly in BCG+papain-treated rats was observed. The lungs of animals treated with BCG+papain showed enhancing of emphysema comparing with the papain-treated rats. Development of emphysematous changes, especially in BCG+papain-treated rats coexisted with cumulation of activated alveolar macrophages and collagen fibres as well as type II alveolar epithelial cells proliferation. Our data support the inflammatory-repair hypothesis of emphysema pathogenesis and indicate that AM regulate collagen production in the lung. Type II alveolar epithelial cells seem be important in lung injury and repair.

  9. The Balloon Experimental Twin Telescope for Infrared Interferometry (BETTII): Spatially Resolved Spectroscopy in the Far-Infrared

    NASA Technical Reports Server (NTRS)

    Rinehart, Stephen

    2009-01-01

    Astronomical studies at infrared wavelengths have dramatically improved our understanding of the universe, and observations with Spitzer, the upcoming Herschel mission, and SOFIA will continue to provide exciting new discoveries. The relatively low angular resolution of these missions, however, is insufficient to resolve the physical scale on which mid-to far-infrared emission arises, resulting in source and structure ambiguities that limit our ability to answer key science questions. Interferometry enables high angular resolution at these wavelengths - a powerful tool for scientific discovery. We will build the Balloon Experimental Twin Telescope for Infrared Interferometry (BETTII), an eight-meter baseline Michelson stellar interferometer to fly on a high-altitude balloon. BETTII's spectral-spatial capability, provided by an instrument using double-Fourier techniques, will address key questions about the nature of disks in young star clusters and active galactic nuclei and the envelopes of evolved stars. BETTII will also lay the technological groundwork for future space interferometers and for suborbital programs optimized for studying extrasolar planets.

  10. The Balloon Experimental Twin Telescope for Infrared Interferometry (BETTII): Spatially Resolved Spectroscopy in the Far-Infrared

    NASA Technical Reports Server (NTRS)

    Rinehart, Stephen

    2009-01-01

    Astronomical studies at infrared wavelengths have dramatically improved our understanding of the universe, and observations with Spitzer, the upcoming Herschel mission, and SOFIA will continue to provide exciting new discoveries. The relatively low angular resolution of these missions, however, is insufficient to resolve the physical scale on which mid-to far-infrared emission arises, resulting in source and structure ambiguities that limit our ability to answer key science questions. Interferometry enables high angular resolution at these wavelengths - a powerful tool for scientific discovery. We will build the Balloon Experimental Twin Telescope for Infrared Interferometry (BETTII), an eight-meter baseline Michelson stellar interferometer to fly on a high-altitude balloon. BETTII's spectral-spatial capability, provided by an instrument using double-Fourier techniques, will address key questions about the nature of disks in young star clusters and active galactic nuclei and the envelopes of evolved stars. BETTII will also lay the technological groundwork for future space interferometers and for suborbital programs optimized for studying extrasolar planets.

  11. Experimental evaluation of angularly-variable fiber geometry for targeting depth-resolved reflectance from layered epithelial tissue phantoms

    NASA Astrophysics Data System (ADS)

    Wang, Adrien; Nammalvar, Vengadesan; Drezek, Rebekah

    2007-02-01

    The aim of the present study focuses on experimentally demonstrating the efficacy of using angularly-variable fiber geometry to achieve the desired tissue-layer selection and probing depths with the further objective of enhancing the sensitivity and specificity of spectral diagnosis in stratified architectures that resemble human cervical epithelia. The morphological and biochemical features of epithelial tissue vary in accordance with tissue depths; consequently, the accuracy of spectroscopic diagnosis of epithelial dysplasia may be enhanced by probing the optical properties of this tissue. When correlated to cellular dysplasia, layer-specific changes in tissue optical properties may be deciphered by reflectance spectroscopy coupled with angularly-variable fiber geometry. This study addresses the utility of using such angularly-variable fiber geometry for resolving spatially-specific spectral signatures of tissue pathology. This is accomplished by interpreting and analyzing the reflectance spectra of increasingly dysplastic epithelial tissue in two-layer epithelial phantoms. Spectral sensitivity to tissue abnormalities in the epithelial layer is significantly improved as the obliquity of the collection fibers increases from 0 to 40 degrees. Conversely, conventionally orthogonal fibers are found to be more sensitive to changes in stromal tissue properties.

  12. Effectiveness of nitric oxide during spontaneous breathing in experimental lung injury.

    PubMed

    Dembinski, Rolf; Hochhausen, Nadine; Terbeck, Sandra; Bickenbach, Johannes; Stadermann, Frederik; Rossaint, Rolf; Kuhlen, Ralf

    2010-04-01

    Inhaled nitric oxide (iNO) improves gas exchange in about 60% of patients with acute respiratory distress syndrome (ARDS). Recruitment of atelectatic lung areas may improve responsiveness and preservation of spontaneous breathing (SB) may cause recruitment. Accordingly, preservation of SB may improve effectiveness of iNO. To test this hypothesis, iNO was evaluated in experimental acute lung injury (ALI) during SB. In 24 pigs with ALI, effects of 10 ppm iNO were evaluated during controlled mechanical ventilation (CMV) and SB in random order. Preservation of SB was provided by 4 different modes: Unassisted SB was enabled by biphasic positive airway pressure (BIPAP), moderate inspiratory assist was provided by pressure support (PS) and volume-assured pressure support (VAPS), maximum assist was ensured by assist control (A/C). Statistical analysis did not reveal gas exchange improvements due to SB alone. Significant gas exchange improvements due to iNO were only achieved during unassisted SB with BIPAP (P <.05) but not during CMV or assisted SB. The authors conclude that effectiveness of iNO may be improved by unassisted SB during BIPAP but not by assisted SB. Thus combined iNO and unassisted SB is possibly most effective to improve gas exchange in severe hypoxemic ARDS.

  13. An experimental model of aortic surgery and the effect of Iloprost on lung injury.

    PubMed

    Iscan, Sahin; Huseyin, Serhat; Ozdemir, A Coskun; Yalta, Tulin; Yuksel, Volkan; Aksu, Volkan; Ege, Turan

    2013-08-01

    Ischemia/reperfusion (I/R) damage of the lung is a frequently encountered complication following aortic surgery. The aim of the present study is to investigate the histopathological effects of Iloprost on pulmonary damage developed after I/R. Twenty-four Sprague-Dawley rats were randomly divided into 3 groups. In the control group, aortas were not clamped. In the I/R group, aortas were occluded, and after 1 h of ischemia, clamps were removed. After 2 h of reperfusion period, lungs of the rats were extracted. In the I/R + Iloprost group after 1 h of ischemia, Iloprost infusion was initiated, and maintained for the duration of 2 h reperfusion period. For histopathological scoring, density of polymorphonuclear leucocytes, congestion, interstitial edema, and bleeding were semiquantitatively evaluated, and histopathological changes were scored. In the I/R group, multifocal-marked histopathological changes in 5 (62.5%), and multifocal-moderate histopathological changes in 3 (37.5%) rats were detected. In the I/R + Iloprost group, multifocal-moderate histopathological changes in 4 (50%), and multifocal-mild changes in 4 (50%) rats were detected. In the experimental rat model, administration of Iloprost has been shown to have preventive effects for pulmonary damage occurring after I/R generated by infrarenal aortic occlusion.

  14. Infrared long nanosecond laser pulse ablation of silicon: Integrated two-dimensional modeling and time-resolved experimental study

    NASA Astrophysics Data System (ADS)

    Tao, Sha; Zhou, Yun; Wu, Benxin; Gao, Yibo

    2012-07-01

    Nanosecond (ns) laser ablation may provide good solutions to many industrial silicon micromachining applications. However, most of the previous work is on lasers in ultraviolet (UV) or visible spectral ranges, and ns laser ablation of silicon at the infrared (IR) wavelength has not been well understood, particularly for long ns pulses with durations on the order of ∼100 ns. IR ns lasers often have lower costs and less external energy consumption for the same laser energy output than UV or visible lasers, which is desirable for many practical applications. This paper aims to understand the mechanism of IR ns laser ablation of silicon, by combining time-resolved experimental observations with physics-based modeling study. The observation is through a ns-gated intensified charged-coupled devices (ICCD) camera coupled with a microscope tube, while the model is based on two-dimensional (2D) gas dynamic equations for the gaseous phases coupled with the condensed phase heat transfer equation through the Knudsen layer relations. The research shows that the material removal mechanism under the studied laser ablation conditions is surface vaporization in the early stage (yielding a plasma plume above the target), followed by subsequent liquid ejection. The measured plasma front propagation matches reasonably well with the model prediction. The experimentally observed spatial distribution of the plasma radiation intensity is consistent with and has been understood through the model. The study also shows that the observed liquid ejection is induced by the total surface pressure difference between the near-boundary region of the target melt pool and the other remaining region of the pool. The pressure difference is mainly due to the surface vaporization flux drop after laser pulse ends.

  15. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host–pathogen interactions in cystic fibrosis

    PubMed Central

    MOSER, CLAUS; VAN GENNIP, MARIA; BJARNSHOLT, THOMAS; JENSEN, PETER ØSTRUP; LEE, BAOLERI; HOUGEN, HANS PETTER; CALUM, HENRIK; CIOFU, OANA; GIVSKOV, MICHAEL; MOLIN, SØREN; HØIBY, NIELS

    2009-01-01

    The dominant cause of premature death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes significant genetic changes, resulting in diversifying geno- and phenotypes. Such an adaptation may generate different host responses. To experimentally reflect the year-long chronic lung infection in CF, groups of BALB/c mice were infected with clonal isolates from different periods (1980, 1988, 1997, 1999 and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non-mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production of macrophage inflammatory protein-2 (MIP-2) and granulocyte colony-stimulating factor (G-CSF). In contrast, the mucoid clones were more virulent and virulence increased with time, resulting in impaired pulmonary clearing of the latest clone, severe inflammation and increased pulmonary MIP-2 and G-CSF production. In conclusion, adaptation of P. aeruginosa in CF is reflected by changed ability to establish lung infection and results in distinct host responses to mucoid and non-mucoid phenotypes. PMID:19239431

  16. Experimental investigation of particle deposition mechanisms in the lung acinus using microfluidic models.

    NASA Astrophysics Data System (ADS)

    Fishler, Rami; Mulligan, Molly; Dubowski, Yael; Sznitman, Josue; Sznitman Lab-department of Biomedical Engineering Team; Dubowski Lab-faculty of Civil; Environmental Engineering Team

    2014-11-01

    In order to experimentally investigate particle deposition mechanisms in the deep alveolated regions of the lungs, we have developed a novel microfluidic device mimicking breathing acinar flow conditions directly at the physiological scale. The model features an anatomically-inspired acinar geometry with five dichotomously branching airway generations lined with periodically expanding and contracting alveoli. Deposition patterns of airborne polystyrene microspheres (spanning 0.1 μm to 2 μm in diameter) inside the airway tree network compare well with CFD simulations and reveal the roles of gravity and Brownian motion on particle deposition sites. Furthermore, measured trajectories of incense particles (0.1-1 μm) inside the breathing device show a critical role for Brownian diffusion in determining the fate of inhaled sub-micron particles by enabling particles to cross from the acinar ducts into alveolar cavities, especially during the short time lag between inhalation and exhalation phases.

  17. Viral Replication and Lung Lesions in BALB/c Mice Experimentally Inoculated with Avian Metapneumovirus Subgroup C Isolated from Chickens

    PubMed Central

    She, Ruiping; Hu, Fengjiao; Wang, Jing; Yan, Xu; Zhang, Chunyan; Liu, Shuhang; Quan, Rong; Li, Zixuan; Du, Fang; Wei, Ting; Liu, Jue

    2014-01-01

    Avian metapneumovirus (aMPV) emerged as an important respiratory pathogen causing acute respiratory tract infection in avian species. Here we used a chicken aMPV subgroup C (aMPV/C) isolate to inoculate experimentally BALB/c mice and found that the aMPV/C can efficiently replicate and persist in the lungs of mice for at least 21 days with a peak viral load at day 6 postinoculation. Lung pathological changes were characterized by increased inflammatory cells. Immunochemical assay showed the presence of viral antigens in the lungs and significant upregulation of pulmonary inflammatory cytokines and chemokines including MCP-1, MIP-1α, RANTES, IL-1β, IFN-γ, and TNF-α were detected following inoculation. These results indicate for the first time that chicken aMPV/C may replicate in the lung of mice. Whether aMPV/C has potential as zoonotic pathogen, further investigation will be required. PMID:24637582

  18. Sevoflurane anesthetic preconditioning protects the lung endothelial glycocalyx from ischemia reperfusion injury in an experimental lung autotransplant model.

    PubMed

    Casanova, Javier; Simon, Carlos; Vara, Elena; Sanchez, Guillermo; Rancan, Lisa; Abubakra, Selma; Calvo, Alberto; Gonzalez, Francisco Jose; Garutti, Ignacio

    2016-10-01

    The glycocalyx is a glycoprotein-polysaccaride layer covering the endothelium luminal surface, and plays a key regulatory role in several endothelial functions. Lung ischemia reperfusion (IR) is a clinical entity that occurs in everyday thoracic surgery and causes glycocalix destruction and a florid local and systemic immune response. Moreover, sevoflurane is able to modulate the inflammatory response triggered by IR lung injury. In this study, we evaluated the protective effects of sevoflurane on the pulmonary endothelial glycocalyx in an in-vivo lung autotransplant model in pigs. Sixteen Large White pigs underwent pneumonectomy plus lung autotransplant. They were divided into two groups depending on the hypnotic agent received (propofol or anesthetic preconditioning with sevoflurane). Glycocalyx components (syndecan-1 and heparan sulphate), cathepsin B, chemokines (MCP-1, MIP-1, and MIP-2) and adhesion molecules (VCAM and ICAM-1) were measured at four different timepoints using porcine-specific enzyme-linked immunosorbent assay (ELISA) kits. There were no differences between groups in weight or in surgical and one-lung ventilation time. Greater glycocalyx destruction and higher chemokine and adhesion molecule expression were observed in the group that did not receive sevoflurane. Heparan sulphate and serum syndecan levels were higher in the propofol group (P < 0.0001) after reperfusion, as was cathepsin B activity (P < 0.015). MCP-1, MIP-1, MIP-2, VCAM, and ICAM-1 levels were also higher in the propofol group (P < 0.006). Sevoflurane preconditioning protects pulmonary glycocalyx and reduces expression of leukocyte chemokines in an in-vivo model of pulmonary IR.

  19. COMPARISON OF LUNG ATTENUATION AND HETEROGENEITY BETWEEN CATS WITH EXPERIMENTALLY INDUCED ALLERGIC ASTHMA, NATURALLY OCCURRING ASTHMA AND NORMAL CATS.

    PubMed

    Masseau, Isabelle; Banuelos, Alina; Dodam, John; Cohn, Leah A; Reinero, Carol

    2015-01-01

    Airway remodeling is a prominent feature of feline allergic asthma but requires biopsy for characterization. Computed tomography (CT) has appeal as a minimally invasive diagnostic test. The purpose of this prospective case-control study was to compare indices of airway remodeling between cats with experimentally induced, spontaneous asthma and healthy unaffected cats using CT. We hypothesized that experimental and spontaneous feline asthma would have similar CT airway remodeling characteristics and that these would be significantly different in healthy cats. Experimentally induced asthmatic research cats (n = 5), spontaneously asthmatic pet cats (n = 6), and healthy research cats (n = 5) were scanned unrestrained using a 64-detector row CT scanner. Inspiratory breath-hold CT scans were also performed in experimentally induced asthmatic and healthy cats. Mean ± extent variation of lung attenuation for each cat was determined using an airway inspector software program and CT images were scored for lung heterogeneity by a board-certified veterinary radiologist who was unaware of cat group status. Groups were compared using one-way ANOVA (unrestrained scans) and the Student's t-test (anesthetized scans) with significance defined as P < 0.10. Experimentally asthmatic and spontaneously asthmatic cats had significantly (P = 0.028 and P = 0.073, respectively) increased lung attenuation compared to healthy cats. Heterogeneity scores were higher in experimentally induced asthmatic cat than in healthy cats. Objective quantification of lung heterogeneity and lung volume did not differ among the three groups (P = 0.311, P = 0.181, respectively). Findings supported our hypothesis. Inspiratory breath-hold anesthetized CT scans facilitated discrimination between asthmatic and healthy cats in comparison to unrestrained CT scans.

  20. RC-3095, a selective gastrin-releasing peptide receptor antagonist, does not protect the lungs in an experimental model of lung ischemia-reperfusion injury.

    PubMed

    Oliveira-Freitas, Vera L; Thomaz, Leonardo Dalla Giacomassa Rocha; Simoneti, Lucas Elias Lise; Malfitano, Christiane; De Angelis, Kátia; Ulbrich, Jane Maria; Schwartsmann, Gilberto; Andrade, Cristiano Feijó

    2015-01-01

    RC-3095, a selective GRPR antagonist, has been shown to have anti-inflammatory properties in different models of inflammation. However, its protective effect on lungs submitted to lung ischemia-reperfusion injury has not been addressed before. Then, we administrated RC-3095 intravenously before and after lung reperfusion using an animal model of lung ischemia-reperfusion injury (LIRI) by clamping the pulmonary hilum. Twenty Wistar rats were subjected to an experimental model in four groups: SHAM, ischemia-reperfusion (IR), RC-Pre, and RC-Post. The final mean arterial pressure significantly decreased in IR and RC-Pre compared to their values before reperfusion (P < 0.001). The RC-Post group showed significant decrease of partial pressure of arterial oxygen at the end of the observation when compared to baseline (P = 0.005). Caspase-9 activity was significantly higher in the RC-Post as compared to the other groups (P < 0.013). No significant differences were observed in eNOS activity among the groups. The groups RC-Pre and RC-Post did not show any significant decrease in IL-1β (P = 0.159) and TNF-α (P = 0.260), as compared to IR. The histological score showed no significant differences among the groups. In conclusion, RC-3095 does not demonstrate a protective effect in our LIRI model. Additionally, its use after reperfusion seems to potentiate cell damage, stimulating apoptosis.

  1. Lung preservation in experimental ischemia/reperfusion injury and lung transplantation: a comparison of natural and synthetic surfactants.

    PubMed

    Knudsen, Lars; Boxler, Laura; Mühlfeld, Christian; Schaefer, Inga-Marie; Becker, Laura; Bussinger, Christine; von Stietencron, Immanuel; Madershahian, Navid; Richter, Joachim; Wahlers, Thorsten; Wittwer, Thorsten; Ochs, Matthias

    2012-01-01

    Surfactant inactivation results from ischemia/reperfusion injury and plays a major role in the pathogenesis of primary graft dysfunction after clinical lung transplantation. Thus, prophylactic administration of exogenous surfactant preparations before the onset of ischemia/reperfusion has proven to be effective in preserving pulmonary structure and function. Various natural and synthetic surfactant preparations exhibit differences regarding the biochemical composition and biophysical properties. In this study we compared the efficacy of preservation of pulmonary structure and function of the natural surfactant preparations Curosurf and Survanta to that of a synthetic surfactant containing an analog of surfactant protein C (SPC-33) in a rat model of ischemia/reperfusion injury. The oxygenation capacity and peak inspiratory pressure during the reperfusion period were recorded. By applying design-based stereology at the light- and electron-microscopic level, pathologic alterations, including alveolar edema, injury of the blood-air barrier and the intra-alveolar as well as intracellular surfactant pools, were quantified. The best oxygenation and preservation of lung structure was achieved with Curosurf. Survanta treatment was associated with the most severe injury of the blood-air barrier, and SPC-33 demonstrated signs of microatelectasis. The intra-alveolar surfactant pool after Curosurf and SPC-33 was dominated by active surfactant subtypes, whereas Survanta was associated with the highest fraction of inactive surfactant. The intracellular surfactant pool did not show any differences between the treatment groups. Taken together, Curosurf achieved the best structural and functional lung preservation, whereas Survanta was inferior to both Curosurf and SPC-33. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Effects of Nigella sativa seed extract on ameliorating lung tissue damage in rats after experimental pulmonary aspirations.

    PubMed

    Kanter, Mehmet

    2009-01-01

    Aspiration of gastric contents can cause serious lung injury, although the mechanisms of pulmonary damage are still not clear and means of amelioration of the pulmonary damage have been little investigated. The black cumin seed, Nigella sativa L. (NS) has been shown to have specific health benefits and the aim of the current study was to investigate the possible beneficial effects of NS on experimental lung injury in male Wistar rats after pulmonary aspiration of different materials. The rats were randomly allotted into one of six experimental groups (n=7 per group): (1) saline control, (2) saline+NS treated, (3) Pulmocare (a specialized nutritional supplement given to pulmonary patients), (4) Pulmocare+NS treated, (5) hydrochloric acid, (6) hydrochloric acid+NS treated. The saline, Pulmocare and hydrochloric acid were injected into the lungs in a volume of 2 ml/kg. The rats received daily oral doses of NS volatile oil (400mg/kg body weight) by means of intragastric intubation for 7 days starting immediately after the pulmonary aspiration of the materials. After 7 days, the rats were sacrificed and tissue samples from both lungs were taken for histopathological investigation. To date, no similar study investigating the potential for NS treatment to protect against lung injury after pulmonary aspiration of materials has been reported. Our study showed that NS treatment inhibits the inflammatory pulmonary responses, reducing significantly (p<0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar macrophages, interstitial fibrosis, granuloma and necrosis formation in different pulmonary aspiration models. Our data indicate a significant reduction in the activity of inducible nitric oxide synthase (iNOS) and a rise in surfactant protein D in lung tissue of different pulmonary aspiration models after NS therapy. Based on our results, we conclude that NS treatment might be beneficial in lung injury and

  3. Understanding Lung Deposition of Alpha-1 Antitrypsin in Acute Experimental Mouse Lung Injury Model Using Fluorescence Microscopy

    PubMed Central

    Zhan, Yutian; Chen, Jianqing; Rong, Haojing; O'Neil, Shawn P.; Ghosh, Brahma; Nguyen, Vuong; Li, Xianfeng

    2016-01-01

    Human plasma-derived α1-antitrypsin (AAT) delivered by intravenous infusion is used as augmentation therapy in patients with emphysema who have a genetic mutation resulting in deficiency of AAT. Inhalation is an alternative route of administration that can potentially increase the efficacy and convenience of treatment. This study was conducted to determine whether delivery to the lungs, initially via the intratracheal (IT) route of administration, would deliver efficacious levels of a recombinant AAT (rAAT) to the site of action in the lungs in mice. 125I-radiolabeled rAAT, fluorophore-conjugated rAAT (rAAT-Alexa488), and NE680 (neutrophil elastase 680, a silent fluorescent substrate of neutrophil elastase which fluoresces in the near-infrared range upon activation by neutrophil elastase) were used to characterize the pharmacokinetics and tissue distribution profile, distribution of rAAT within the lung, and efficacy of rAAT to inhibit neutrophil elastase at the site of action, respectively. The study has demonstrated that rAAT was able to gain access to locations where neutrophil elastase was localized. The histochemical quantification of rAAT activity relative to dose at the site of action provided here will improve confidence in predicting the human dose via the inhalation route. PMID:28050284

  4. Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis

    PubMed Central

    2013-01-01

    Introduction Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. Methods Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. Results Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. Conclusions These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory

  5. Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.

    PubMed

    Wilson, Joel; Higgins, David; Hutting, Haley; Serkova, Natalie; Baird, Christine; Khailova, Ludmila; Queensland, Kelly; Vu Tran, Zung; Weitzel, Lindsay; Wischmeyer, Paul E

    2013-09-10

    Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection.

  6. Computational Fluid Dynamics and Experimental Characterization of the Pediatric Pump-Lung.

    PubMed

    Wu, Zhongjun J; Gellman, Barry; Zhang, Tao; Taskin, M Ertan; Dasse, Kurt A; Griffith, Bartley P

    2011-12-01

    The pediatric pump-lung (PediPL) is a miniaturized integrated pediatric pump-oxygenator specifically designed for cardiac or cardiopulmonary support for patients weighing 5-20 kg to allow mobility and extended use for 30 days. The PediPL incorporates a magnetically levitated impeller with uniquely configured hollow fiber membranes into a single unit capable of performing both pumping and gas exchange. A combined computational and experimental study was conducted to characterize the functional and hemocompatibility performances of this newly developed device. The three-dimensional flow features of the PediPL and its hemolytic characteristics were analyzed using computational fluid dynamics based modeling. The oxygen exchange was modeled based on a convection-diffusion-reaction process. The hollow fiber membranes were modeled as a porous medium which incorporates the flow resistance in the bundle by an added momentum sink term. The pumping function was evaluated for the required range of operating conditions (0.5-2.5 L/min and 1000-3000 rpm). The blood damage potentials were further analyzed in terms of flow and shear stress fields, and the calculations of hemolysis index. In parallel, the hydraulic pump performance, oxygen transfer and hemolysis level were quantified experimentally. Based on the computational and experimental results, the PediPL device is found to be functional to provide necessary oxygen transfer and blood pumping requirements for the pediatric patients. Smooth blood flow characteristics and low blood damage potential were observed in the entire device. The in-vitro tests further confirmed that the PediPL can provide adequate blood pumping and oxygen transfer over the range of intended operating conditions with acceptable hemolytic performance. The rated flow rate for oxygenation is 2.5 L/min. The normalized index of hemolysis is 0.065 g/100L at 1.0 L/min and 3000 rpm.

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

    PubMed

    Henzler, Dietrich; Mahnken, Andreas H; Wildberger, Joachim E; Rossaint, Rolf; Günther, Rolf W; Kuhlen, Ralf

    2006-06-01

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

  8. Lung Cancer Stem Cell: New Insights on Experimental Models and Preclinical Data

    PubMed Central

    Rivera, Caroline; Rivera, Sofia; Loriot, Yohann; Vozenin, Marie-Catherine; Deutsch, Eric

    2011-01-01

    Lung cancer remains the leading cause of cancer death. Understanding lung tumors physiopathology should provide opportunity to prevent tumor development or/and improve their therapeutic management. Cancer stem cell (CSC) theory refers to a subpopulation of cancer cells, also named tumor-initiating cells, that can drive cancer development. Cells presenting these characteristics have been identified and isolated from lung cancer. Exploring cell markers and signaling pathways specific to lung CSCs may lead to progress in therapy and improve the prognosis of patients with lung cancer. Continuous efforts in developing in vitro and in vivo models may yield reliable tools to better understand CSC abilities and to test new therapeutic targets. Preclinical data on putative CSC targets are emerging by now. These preliminary studies are critical for the next generation of lung cancer therapies. PMID:21209720

  9. Changes in breath sound power spectra during experimental oleic acid-induced lung injury in pigs.

    PubMed

    Räsänen, Jukka; Nemergut, Michael E; Gavriely, Noam

    2014-01-01

    To evaluate the effect of acute lung injury on the frequency spectra of breath sounds, we made serial acoustic recordings from nondependent, midlung and dependent regions of both lungs in ten 35- to 45-kg anesthetized, intubated, and mechanically ventilated pigs during development of acute lung injury induced with intravenous oleic acid in prone or supine position. Oleic acid injections rapidly produced severe derangements in the gas exchange and mechanical properties of the lung, with an average increase in venous admixture from 16 ± 12 to 62 ± 16% (P < 0.01), and a reduction in dynamic respiratory system compliance from 25 ± 4 to 14 ± 4 ml/cmH2O (P < 0.01). A concomitant increase in sound power was seen in all lung regions (P < 0.05), predominantly in frequencies 150-800 Hz. The deterioration in gas exchange and lung mechanics correlated best with concurrent spectral changes in the nondependent lung regions. Acute lung injury increases the power of breath sounds likely secondary to redistribution of ventilation from collapsed to aerated parts of the lung and improved sound transmission in dependent, consolidated areas.

  10. /sup 111/In-platelet and /sup 125/I-fibrinogen deposition in the lungs in experimental acute pancreatitis

    SciTech Connect

    Goulbourne, I.A.; Watson, H.; Davies, G.C.

    1987-12-01

    An experimental model of acute pancreatitis in rats has been used to study intrapulmonary /sup 125/I-fibrinogen and /sup 111/In-platelet deposition. Pancreatitis caused a significant increase in wet lung weight compared to normal, and this could be abolished by heparin or aspirin pretreatment. /sup 125/I-fibrinogen was deposited in the lungs of animals to a significantly greater degree than in controls (P less than 0.01). /sup 125/I-fibrinogen deposition was reduced to control levels by pretreatment with aspirin or heparin (P less than 0.05). The uptake of radiolabeled platelets was greater in pancreatitis than in controls (P less than 0.001). Pancreatitis appears to be responsible for platelet entrapment in the lungs. Platelet uptake was reduced by heparin treatment but unaffected by aspirin therapy.

  11. Immunohistochemical demonstration of influenza A nucleoprotein in lungs of turkeys with natural and experimental influenza respiratory disease.

    PubMed

    Swayne, D E; Ficken, M D; Guy, J S

    1992-12-01

    Influenza A virus (H1N1) and several bacteria were recovered from lungs of turkey breeder hens during a respiratory disease outbreak. Influenza A nucleoprotein was detected in the pneumonic lung tissue within macrophages and, rarely, in atrial-lining epithelium. Inconsistent recovery of pathogenic bacteria suggested that death in some turkeys resulted from acute primary viral pneumonia. In an experimental study, the gross and histologic lesions confirmed the respiratory pathogenicity of the influenza virus. The presence of intranuclear and intracytoplasmic influenza A nucleoprotein within macrophages and atrial lining epithelium of the lung, respiratory epithelium of the trachea and hypertrophied epithelial cells of the airsacs verified influenza virus replication in the respiratory system. However, the absence of mortality may suggest that secondary factors, such as bacteria, may modify the disease in natural outbreaks.

  12. [Effect of dexmedetomidine on acute lung injury in experimental ischemia-reperfusion model].

    PubMed

    Küçükebe, Ömer Burak; Özzeybek, Deniz; Abdullayev, Ruslan; Ustaoğlu, Adil; Tekmen, Işıl; Küme, Tuncay

    Ischemia-reperfusion injury is one of the consequences of tourniquet application for extremity surgery. The aim of the study was to establish the effect of dexmedetomidine on the acute lung injury following lower extremity experimental ischemia-reperfusion model in rats. Twenty-eight Wistar-Albino breed rats were recruited after Ethics Committee approval and allocated into 4 groups, each with 7 subjects. Group 1 (SHAM) received only anesthesia. Group 2 (IR) had experienced 3h of ischemia and 3h of reperfusion using left lower extremity tourniquet after anesthesia application. Groups 3 (D-50) and 4 (D-100) had undergone the same procedures as in the Group 2, except for receiving 50 and 100mg.kg(-1), respectively, dexmedetomidine intraperitoneally 1h before the tourniquet release. Blood samples were obtained for the analysis of tumor necrosing factor-α and interleukin-6. Pulmonary tissue samples were obtained for histological analysis. No significant difference regarding blood tumor necrosing factor-α and interleukin-6 values was found among the groups, whereas pulmonary tissue injury scores revealed significant difference. Histological scores obtained from the Group 2 were significantly higher from those in the Groups 1, 3 and 4 with p-values 0.001 for each comparison. Moreover, Group 1 scores were found to be significantly lower than those in the Groups 3 and 4 with p-values 0.001 and 0.011, respectively. No significant difference was observed between the Groups 3 and 4. Dexmedetomidine is effective in reduction of the experimental ischemia-reperfusion induced pulmonary tissue injury in rats, formed by extremity tourniquet application. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  13. WNT/β-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury.

    PubMed

    Villar, Jesús; Cabrera, Nuria E; Casula, Milena; Valladares, Francisco; Flores, Carlos; López-Aguilar, Josefina; Blanch, Lluis; Zhang, Haibo; Kacmarek, Robert M; Slutsky, Arthur S

    2011-07-01

    The mechanisms involved in lung injury progression during acute lung injury (ALI) are still poorly understood. Because WNT/β-catenin signaling has been shown to be involved in epithelial cell injury and hyperplasia during inflammation and sepsis, we hypothesized that it would be modulated by mechanical ventilation (MV) in an experimental model of sepsis-induced ALI. This study was a prospective, randomized, controlled animal study performed using adult male Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. At 18 h, surviving animals were randomized to spontaneous breathing or two strategies of MV for 4 h: low tidal volume (V (T)) (6 ml/kg) plus 10 cmH2O of positive end-expiratory pressure (PEEP) versus high (20 ml/kg) tidal volume (V (T)) with zero PEEP. Histological evaluation, measurements of WNT5A, total β-catenin, and matrix metalloproteinase-7 (MMP7) protein levels by Western blot, and their immunohistochemical localization in the lungs were analyzed. Sepsis and high-V (T) MV caused lung inflammation and perivascular edema with cellular infiltrates and collagen deposition. Protein levels of WNT5A, β-catenin, and MMP7 in the lungs were increased in animals with sepsis-induced ALI. High-V (T) MV was associated with higher levels of WNT5A, β-catenin, and MMP7 protein levels (p < 0.001), compared to healthy control animals. By contrast, low-V (T) MV markedly reduced WNT5A, β-catenin, and MMP7 protein levels (p < 0.001). Our findings demonstrate that the WNT/β-catenin signaling pathway is modulated early during sepsis and ventilator-induced lung injury, suggesting that activation of this pathway could play an important role in both lung injury progression and repair.

  14. Harmonic technology versus neodymium-doped yttrium aluminium garnet laser and electrocautery for lung metastasectomy: an experimental study.

    PubMed

    Fiorelli, Alfonso; Accardo, Marina; Carelli, Emanuele; Del Prete, Assunta; Messina, Gaetana; Reginelli, Alfonso; Berritto, Daniela; Papale, Ferdinando; Armenia, Emilia; Chiodini, Paolo; Grassi, Roberto; Santini, Mario

    2016-07-01

    found; however, they ceased by sealing lung parenchyma with harmonic technology. Our experimental data support the resections performed with the use of harmonic technology. The lack of severe tissue alterations could favour healing of parenchyma, assure air tightness and preserve functional lung parenchyma. However, randomized controlled studies are needed in an in vivo model to corroborate our findings. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  15. Effects of short-term propofol and dexmedetomidine on pulmonary morphofunction and biological markers in experimental mild acute lung injury.

    PubMed

    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.

  16. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals.

    PubMed

    Matute-Bello, Gustavo; Downey, Gregory; Moore, Bethany B; Groshong, Steve D; Matthay, Michael A; Slutsky, Arthur S; Kuebler, Wolfgang M

    2011-05-01

    Acute lung injury (ALI) is well defined in humans, but there is no agreement as to the main features of acute lung injury in animal models. A Committee was organized to determine the main features that characterize ALI in animal models and to identify the most relevant methods to assess these features. We used a Delphi approach in which a series of questionnaires were distributed to a panel of experts in experimental lung injury. The Committee concluded that the main features of experimental ALI include histological evidence of tissue injury, alteration of the alveolar capillary barrier, presence of an inflammatory response, and evidence of physiological dysfunction; they recommended that, to determine if ALI has occurred, at least three of these four main features of ALI should be present. The Committee also identified key "very relevant" and "somewhat relevant" measurements for each of the main features of ALI and recommended the use of least one "very relevant" measurement and preferably one or two additional separate measurements to determine if a main feature of ALI is present. Finally, the Committee emphasized that not all of the measurements listed can or should be performed in every study, and that measurements not included in the list are by no means "irrelevant." Our list of features and measurements of ALI is intended as a guide for investigators, and ultimately investigators should choose the particular measurements that best suit the experimental questions being addressed as well as take into consideration any unique aspects of the experimental design.

  17. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model

    PubMed Central

    Huang, Kun-Lun; Lan, Chou-Chin; Hsu, Yu-Juei; Wu, Geng-Chin; Peng, Chia-Hui

    2017-01-01

    Lung ischemia reperfusion injury (LIRI) is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD) on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75%) diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR)-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS), proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB) activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF). The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway. PMID:28291795

  18. Towards predicting the lung fibrogenic activity of nanomaterials: experimental validation of an in vitro fibroblast proliferation assay

    PubMed Central

    2013-01-01

    Background Carbon nanotubes (CNT) can induce lung inflammation and fibrosis in rodents. Several studies have identified the capacity of CNT to stimulate the proliferation of fibroblasts. We developed and validated experimentally here a simple and rapid in vitro assay to evaluate the capacity of a nanomaterial to exert a direct pro-fibrotic effect on fibroblasts. Methods The activity of several multi-wall (MW)CNT samples (NM400, the crushed form of NM400 named NM400c, NM402 and MWCNTg 2400) and asbestos (crocidolite) was investigated in vitro and in vivo. The proliferative response to MWCNT was assessed on mouse primary lung fibroblasts, human fetal lung fibroblasts (HFL-1), mouse embryonic fibroblasts (BALB-3T3) and mouse lung fibroblasts (MLg) by using different assays (cell counting, WST-1 assay and propidium iodide PI staining) and dispersion media (fetal bovine serum, FBS and bovine serum albumin, BSA). C57BL/6 mice were pharyngeally aspirated with the same materials and lung fibrosis was assessed after 2 months by histopathology, quantification of total collagen lung content and pro-fibrotic cytokines in broncho-alveolar lavage fluid (BALF). Results MWCNT (NM400 and NM402) directly stimulated fibroblast proliferation in vitro in a dose-dependent manner and induced lung fibrosis in vivo. NM400 stimulated the proliferation of all tested fibroblast types, independently of FBS- or BSA- dispersion. Results obtained by WST1 cell activity were confirmed with cell counting and cell cycle (PI staining) assays. Crocidolite also stimulated fibroblast proliferation and induced pulmonary fibrosis, although to a lesser extent than NM400 and NM402. In contrast, shorter CNT (NM400c and MWCNTg 2400) did not induce any fibroblast proliferation or collagen accumulation in vivo, supporting the idea that CNT structure is an important parameter for inducing lung fibrosis. Conclusions In this study, an optimized proliferation assay using BSA as a dispersant, MLg cells as targets

  19. Experimental investigations on range-resolved refractive index structure parameter Cn2, by optical measurements over a 2.0 km free space laser path

    NASA Astrophysics Data System (ADS)

    Sudhakar, P.; Sheela, K. Anitha; Ramakrishna Rao, D.; Satyanarayana, Malladi

    2016-05-01

    There is growing interest in development of electro-optical systems capable of operation over long atmospheric distances in various atmospheric conditions. Some of these systems include laser communications, remote sensing, active and passive imaging, target tracking and designation and laser beam projection (directed energy) systems. As increasingly sophisticated electro-optical systems are used in the atmosphere, the character of the medium becomes important. Optical turbulence is one of the most important characteristics for propagation through the atmosphere. A single ended experimental setup using the Nd: YAG laser operating at 1064nm is used to study the temporal and spatial variations of refractive index structure parameter Cn2 experimentally. In this paper we present the details of the experimental setup used for the measurement of range resolved refractive index structure parameter Cn2, over a two way slant 4.0 km free space laser path. Some of the results obtained using the experimental setup are presented and discussed.

  20. An experimental study of sampling time effects on the resolving power of on-line two-dimensional High Performance Liquid Chromatography

    PubMed Central

    Huang, Yuan; Gu, Haiwei; Filgueira, Marcelo; Carr, Peter W.

    2011-01-01

    The experimental effects of sampling time on the resolving power of on-line LC×LC were investigated. The first dimension gradient time (1tg) and sampling time (ts) were systematically varied (1tg = 5, 12, 24 and 49 min; ts = 6, 12, 21 and 40 s). The resolving power of on-line LC×LC was evaluated in terms of two metrics namely the numbers of observed peaks and the effective 2D peak capacities obtained in separations of extracts of maize seeds. The maximum effective peak capacity and number of observed peaks of LC×LC was always achieved at sampling times between 12 and 21 s, at all first dimension gradient times. In addition, both metrics showed that the “crossover” time at which fully optimized 1DLC and LC×LC have equal resolving power varied somewhat with sampling time but is only about 5 minutes for sampling times of 12 and 21 s. The longest crossover time was obtained when the sampling time was 6 s. Furthermore, increasing the first dimension gradient time gave large improvements in the resolving power of LC×LC relative to 1DLC. Finally, comparisons of the corrected and effective 2D peak capacities as well as the number of peaks observed showed that the impact of the coverage factor is quite significant. PMID:21489543

  1. Effect of partial liquid ventilation on pulmonary vascular permeability and edema after experimental acute lung injury.

    PubMed

    Lange, N R; Kozlowski, J K; Gust, R; Shapiro, S D; Schuster, D P

    2000-07-01

    We evaluated the effects of partial liquid ventilation (PLV) with two different dosages of the perfluorocarbon LiquiVent (perflubron) on pulmonary vascular permeability and edema formation after oleic acid (OA)-induced acute lung injury in dogs. We used imaging with positron emission tomography to measure fractional pulmonary blood flow, lung water concentration (LWC), and the pulmonary transcapillary escape rate (PTCER) of (68)Ga-labeled transferrin at 5 and 21 h after lung injury in five dogs undergoing conventional mechanical ventilation (CMV), five dogs undergoing low-dose PLV (perflubron at 10 ml/kg), and four dogs undergoing high dose PLV (perflubron at 30 ml/kg). A positive end-expiratory pressure of 7.5 cm H(2)O was used in all dogs. After OA (0.08 ml/kg)- induced lung injury, there were no significant differences or trends for PTCER or LWC at any time when the PLV groups were compared with the CMV group. However, lung tissue myeloperoxidase activity was significantly lower in the combined PLV group than in the CMV group (p = 0.016). We conclude that after OA-induced lung injury, the addition of PLV to CMV does not directly attenuate pulmonary vascular leak or lung water accumulation. Rather, the benefits of such treatment may be due to modifications of the inflammatory response.

  2. Pivotal Role of the 5-Lipoxygenase Pathway in Lung Injury after Experimental Sepsis

    PubMed Central

    Monteiro, Ana Paula T.; Soledade, Erico; Pinheiro, Carla S.; Dellatorre-Teixeira, Ludmilla; Oliveira, Gisele P.; Oliveira, Mariana G.; Peters-Golden, Marc; Rocco, Patricia R. M.; Benjamim, Claudia F.

    2014-01-01

    Postsepsis lung injury is a common clinical problem associated with significant morbidity and mortality. Leukotrienes (LTs) are important lipid mediators of infection and inflammation derived from the 5-lipoxygenase (5-LO) metabolism of arachidonate with the potential to contribute to lung damage after sepsis. To test the hypothesis that LTs are mediators of lung injury after sepsis, we assessed lung structure, inflammatory mediators, and mechanical changes after cecal ligation and puncture surgery in wild-type (WT) and 5-LO knockout (5-LO−/−) mice and in WT mice treated with a pharmacologic LT synthesis inhibitor (MK886) and LT receptor antagonists (CP105,696 and montelukast). Sixteen hours after surgery, WT animals exhibited severe lung injury (by histological analysis), substantial mechanical impairment (i.e., an increase in static lung elastance), an increase in neutrophil infiltration, and high levels of LTB4, cysteinyl-LTs (cys-LTs), prostaglandin E2, IL-1β, IL-6, IL-10, IL-17, KC (CXCL1), and monocyte chemotactic protein–1 (CCL2) in lung tissue and plasma. 5-LO−/− mice and WT mice treated with a pharmacologic 5-LO inhibitor were significantly protected from lung inflammation and injury. Selective antagonists for BLT1 or cys-LT1, the high-affinity receptors for LTB4 and cys-LTs, respectively, were insufficient to provide protection when used alone. These results point to an important role for 5-LO products in sepsis-induced lung injury and suggest that the use of 5-LO inhibitors may be of therapeutic benefit clinically. PMID:23947598

  3. Pivotal role of the 5-lipoxygenase pathway in lung injury after experimental sepsis.

    PubMed

    Monteiro, Ana Paula T; Soledade, Erico; Pinheiro, Carla S; Dellatorre-Teixeira, Ludmilla; Oliveira, Gisele P; Oliveira, Mariana G; Peters-Golden, Marc; Rocco, Patricia R M; Benjamim, Claudia F; Canetti, Claudio

    2014-01-01

    Postsepsis lung injury is a common clinical problem associated with significant morbidity and mortality. Leukotrienes (LTs) are important lipid mediators of infection and inflammation derived from the 5-lipoxygenase (5-LO) metabolism of arachidonate with the potential to contribute to lung damage after sepsis. To test the hypothesis that LTs are mediators of lung injury after sepsis, we assessed lung structure, inflammatory mediators, and mechanical changes after cecal ligation and puncture surgery in wild-type (WT) and 5-LO knockout (5-LO(-/-)) mice and in WT mice treated with a pharmacologic LT synthesis inhibitor (MK886) and LT receptor antagonists (CP105,696 and montelukast). Sixteen hours after surgery, WT animals exhibited severe lung injury (by histological analysis), substantial mechanical impairment (i.e., an increase in static lung elastance), an increase in neutrophil infiltration, and high levels of LTB4, cysteinyl-LTs (cys-LTs), prostaglandin E2, IL-1β, IL-6, IL-10, IL-17, KC (CXCL1), and monocyte chemotactic protein-1 (CCL2) in lung tissue and plasma. 5-LO(-/-) mice and WT mice treated with a pharmacologic 5-LO inhibitor were significantly protected from lung inflammation and injury. Selective antagonists for BLT1 or cys-LT1, the high-affinity receptors for LTB4 and cys-LTs, respectively, were insufficient to provide protection when used alone. These results point to an important role for 5-LO products in sepsis-induced lung injury and suggest that the use of 5-LO inhibitors may be of therapeutic benefit clinically.

  4. Innovative pulmonary preservation of non-heart-beating donor grafts in experimental lung transplantation.

    PubMed

    Wittwer, Thorsten; Franke, Ulrich F W; Fehrenbach, Antonia; Ochs, Matthias; Sandhaus, Tim; Dreyer, Niels; Richter, Joachim; Wahlers, Thorsten

    2004-07-01

    Lung transplantation is limited by scarcity of donor organs. Lung retrieval from non-heart-beating donors (NHBD) might have the potential to extend the donor pool and has been reported recently. However, no studies in NHBD exist using the novel approach of retrograde preservation with Perfadex solution. Asystolic heparinized pigs (n = 5/group) were continuously ventilated for 90, 180 or 300 min of warm ischemia. Lungs were then retrogradely preserved with Perfadex and stored at 4 degrees C in inflation. After 3 h of additional cold ischemia, left lung transplantation was performed. Hemodynamics, pO(2)/F(i)O(2) and dynamic compliance were monitored for 5 h. Intrapulmonary lung water was determined by both global wet-to-dry lung weight ratio (W/D ratio) and standard stereological examination of relative volume fractions of intraalveolar edema. All results were compared to sham-operated controls and to lungs obtained from standard heart-beating donors after retrograde preservation with Perfadex and 27 h of cold ischemia. Statistics comprised ANOVA analysis with repeated measures and Mann-Whitney tests. No mortality was observed. During flush preservation of NHBD lungs, continuous elimination of blood clots via the pulmonary artery was observed. Oxygenation, compliance, intraalveolar edema fraction and W/D ratio were comparable between groups, whereas PVR was significantly lower in sham-controls. Use of NHBD lungs is feasible and results in similar postischemic outcome when compared to sham-controls and standard preservation procedures even after 5 h of pre-harvest warm ischemia. Especially, the NHBD with high-risk constellations for intravascular coagulation might benefit from retrograde preservation by elimination of thrombi from the pulmonary circulation. This innovative technique might also be considered in situations, where brain-dead organ donors become hemodynamically unstable prior to onset of organ harvest. Further trials with longer warm and cold ischemic

  5. Comparison of calculated and experimentally resolved rate constants for excitation energy transfer in C-phycocyanin. 1. Monomers

    SciTech Connect

    Debreczeny, M.P.; Sauer, K.; Zhou, J.; Bryant, D.A.

    1995-05-18

    Rate constants for excitation energy transfer in light-harvesting protein, C-phycocyanin (PC), in the monomeric aggregation state, isolated from the cyanobacterium cynechococcus sp. PCC 7002, are calculated, using Foerster theory and compared with the results of time-resolved fluorescence measurements. The assignments of the energy-transfer rate constants in PC monomers are confirmed here by time-resolved fluorescence anisotropy measurements of the PC monomers isolated from both the wild-type and a mutant strain (cpcB/C155S) whose PC is missing the {beta}{sub 155} chromophore. It is concluded that the Foerster model of resonant energy transfer in the weak coupling limit successfully describes the dominant energy-transfer processes in this protein in the monomeric state. 31 refs., 3 figs., 4 tabs.

  6. Pentoxifylline inhibits intercellular adhesion molecule-1 (ICAM-1) and lung injury in experimental phosgene-exposure rats.

    PubMed

    Zhang, Xiao-di; Hou, Jun-Feng; Qin, Xu-Jun; Li, Wen-Li; Chen, Hong-Li; Liu, Rui; Liang, Xin; Hai, Chun-Xu

    2010-09-01

    Phosgene inhalation results in acute lung injury (ALI) mostly, pulmonary edema and even acute respiratory distress syndrome, but there is no specific antidote. Inflammatory cells play an important role in the ALI caused by phosgene. Intercellular adhesion molecule-1 (ICAM-1) is a critical factor for inflammatory organ injury. We hypothesized that pentoxifylline (PTX), an inhibitor of leukocyte activation, would have a protective effect on experimental phosgene-induced lung injury rats by inhibiting ICAM-1. To prove this hypothesis, we used rat models of phosgene (400 ppm x 1 min)-induced injury to investigate: (1) the time course of lung injury (control 1, 3, 6, 12, 24, and 48 h group), including pathological changes in hematoxylin and eosin staining and transmission electron microscope, myeloperoxidase (MPO) activity by colorimetric method and ICAM-1 protein level detected by western blot, (2) At 3 h after phosgene exposure, protective effects of different dosages of PTX (50 mg/kg and 100 mg/kg) administration were evaluated by MPO activity, ICAM-1 differential expression and WBC count in bronchoalveolar lavage fluid. The results showed that inflammatory cells emerged out of lung blood vessels at 3 h after phosgene exposure. The MPO activity of lung tissue increased significantly from 3 to 48 h after phosgene exposure (P < 0.05) and ICAM-1 expression presented a similar change, especially at 3 h and 24 h (P < 0.05). After pretreatment and treatment with PTX (100 mg/kg), significant protective effects were shown (P < 0.05). These data supported our hypothesis that PTX reduced phosgene-induced lung injury, possibly by inhibiting ICAM-1 differential expression.

  7. Comparison of four lung scoring systems for the assessment of the pathological outcomes derived from Actinobacillus pleuropneumoniae experimental infections

    PubMed Central

    2014-01-01

    Background In this study, four lung lesion scoring methods (Slaughterhouse Pleurisy Evaluation System [SPES], Consolidation Lung Lesion Score [LLS], Image analyses [IA] and Ratio of lung weight/body weight [LW/BW]) were compared for the assessment of the different pathological outcomes derived from an Actinobacillus pleuropneumoniae (App) experimental infection model. Moreover, pathological data was coupled with clinical (fever, inappetence and clinical score), production (average daily weigh gain [ADWG]) and diagnostic (PCR, ELISA and bacterial isolation) parameters within the four infection outcomes (peracute, acute, subclinically infected and non-infected). Results From the 61 inoculated animals, 9 were classified as peracute (presence of severe App-like clinical signs and lesions and sudden death or euthanasia shortly after inoculation), 31 as acutely affected (presence of App-like clinical signs and lesions and survival until the end of the experiment), 12 as subclinically infected (very mild or no clinical signs but App infection confirmed) and 9 as non-infected animals (lack of App-like clinical signs and lack of evidence of App infection). A significant correlation between all lung lesion scoring systems was found with the exception of SPES score versus LW/BW. SPES showed a statistically significant association with all clinical, production and diagnostic (with the exception of PCR detection of App in the tonsil) variables assessed. LLS and IA showed similar statistically significant associations as SPES, with the exception of seroconversion against App at necropsy. In contrast, LW/BW was statistically associated only with App isolation in lungs, presence of App-like lesions and ELISA OD values at necropsy. Conclusions In conclusion, SPES, LLS and IA are economic, fast and easy-to-perform lung scoring methods that, in combination with different clinical and diagnostic parameters, allow the characterization of different outcomes after App infection. PMID

  8. Airway pressure-time curve profile (stress index) detects tidal recruitment/hyperinflation in experimental acute lung injury.

    PubMed

    Grasso, Salvatore; Terragni, Pierpaolo; Mascia, Luciana; Fanelli, Vito; Quintel, Michel; Herrmann, Peter; Hedenstierna, Goran; Slutsky, Arthur S; Ranieri, V Marco

    2004-04-01

    To evaluate whether the shape of the airway pressure-time (Paw-t) curve during constant flow inflation corresponds to radiologic evidence of tidal recruitment or tidal hyperinflation in an experimental model of acute lung injury. Prospective randomized laboratory animal investigation. Department of Clinical Physiology, University of Uppsala, Sweden. Anesthetized, paralyzed, and mechanically ventilated pigs. Acute lung injury was induced by lung lavage. During constant inspiratory flow, the Paw-t curve was fitted to a power equation: airway pressure =a x time + c, where coefficient b (stress index) describes the shape of the curve:b = 1, straight curve; b < 1, progressive increase in slope; and b > 1, progressive decrease in slope. Tidal volume (Vt) was 6 mL/kg, and positive end-expiratory pressure was set to obtain a b value between 0.9 and 1.1 before (b = 1) and after (b = 1 after recruiting maneuver) application of a recruiting maneuver. Positive end-expiratory pressure was decreased and Vt increased to obtain 0.9 >b > 0.8 and 0.8 >b > 0.6, whereas positive end-expiratory pressure and Vt were both increased to obtain 1.3 >b > 1.1 and 1.5 >b > 1.3. Experimental conditions sequence was random. Pulmonary computed tomography was obtained during end-expiratory and end-inspiratory occlusions. Tidal recruitment was quantified as nonaerated (between -100 and +100 Hounsfield units) lung area at end-expiration minus end-inspiration. Tidal hyperinflation was quantified as hyperinflated (between -900 and -1000 Hounsfield units) lung area at end-inspiration minus end-expiration. Computed tomography images showed that tidal recruitment and tidal hyperinflation corresponded to b < 1 and b > 1, respectively. Stress index values and tidal recruitment and tidal hyperinflation values were significantly correlated (R =.917 and R =.911, p <.0001, respectively). Shape of the Paw-t curve detects tidal recruitment and tidal hyperinflation.

  9. Imaging tumor angiogenesis in breast cancer experimental lung metastasis with positron emission tomography, near-infrared fluorescence, and bioluminescence

    PubMed Central

    Zhang, Yin; Hong, Hao; Nayak, Tapas R.; Valdovinos, Hector F.; Myklejord, Duane V.; Theuer, Charles P.; Barnhart, Todd E.; Cai, Weibo

    2013-01-01

    The goal of this study was to develop a molecular imaging agent that can allow for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of CD105 expression in metastatic breast cancer. TRC105, a chimeric anti-CD105 monoclonal antibody, was labeled with both a NIRF dye (i.e., IRDye 800CW) and 64Cu to yield 64Cu-NOTA-TRC105-800CW. Flow cytometry analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and NOTA-TRC105-800CW. Serial bioluminescence imaging (BLI) was carried out to non-invasively monitor the lung tumor burden in BALB/c mice, after intravenous injection of firefly luciferase-transfected 4T1 (i.e., fLuc-4T1) murine breast cancer cells to establish the experimental lung metastasis model. Serial PET imaging revealed that fLuc-4T1 lung tumor uptake of 64Cu-NOTA-TRC105-800CW was 11.9 ± 1.2, 13.9 ± 3.9, and 13.4 ± 2.1 %ID/g at 4, 24, and 48 h post-injection respectively (n = 3). Biodistribution studies, blocking fLuc-4T1 lung tumor uptake with excess TRC105, control experiments with 64Cu-NOTA-cetuximab-800CW (which served as an isotype-matched control), ex vivo BLI/PET/NIRF imaging, autoradiography, and histology all confirmed CD105 specificity of 64Cu-NOTA-TRC105-800CW. Successful PET/NIRF imaging of tumor angiogenesis (i.e., CD105 expression) in the breast cancer experimental lung metastasis model warrants further investigation and clinical translation of dual-labeled TRC105-based agents, which can potentially enable early detection of small metastases and image-guided surgery for tumor removal. PMID:23471463

  10. Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation.

    PubMed

    Lagares, David; Busnadiego, Oscar; García-Fernández, Rosa Ana; Kapoor, Mohit; Liu, Shangxi; Carter, David E; Abraham, David; Shi-Wen, Xu; Carreira, Patricia; Fontaine, Benjamin A; Shea, Barry S; Tager, Andrew M; Leask, Andrew; Lamas, Santiago; Rodríguez-Pascual, Fernando

    2012-05-01

    Enhanced adhesive signaling, including activation of focal adhesion kinase (FAK), is a hallmark of fibroblasts from lung fibrosis patients, and FAK has therefore been hypothesized to be a key mediator of this disease. This study was undertaken to characterize the contribution of FAK to the development of pulmonary fibrosis both in vivo and in vitro. FAK expression and activity were analyzed in lung tissue samples from lung fibrosis patients by immunohistochemistry. Mice orally treated with the FAK inhibitor PF-562,271, or with small interfering RNA (siRNA)-mediated silencing of FAK were exposed to intratracheally instilled bleomycin to induce lung fibrosis, and lungs were harvested for histologic and biochemical analysis. Using endothelin 1 (ET-1) as a stimulus, cell adhesion and contraction, as well as profibrotic gene expression, were studied in fibroblasts isolated from wild-type and FAK-deficient mouse embryos. ET-1-mediated FAK activation and gene expression were studied in primary mouse lung fibroblasts, as well as in wild-type and β1 integrin-deficient mouse fibroblasts. FAK expression and activity were up-regulated in fibroblast foci and remodeled vessels from lung fibrosis patients. Pharmacologic or siRNA-mediated targeting of FAK resulted in marked abrogation of bleomycin-induced lung fibrosis in mice. Loss of FAK impaired the acquisition of a profibrotic phenotype in response to ET-1. Profibrotic gene expression leading to myofibroblast differentiation required cell adhesion, and was driven by JNK activation through β1 integrin/FAK signaling. These results implicate FAK as a central mediator of fibrogenesis, and highlight this kinase as a potential therapeutic target in fibrotic diseases. Copyright © 2012 by the American College of Rheumatology.

  11. Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation

    PubMed Central

    Lagares, David; Busnadiego, Oscar; García-Fernández, Rosa Ana; Kapoor, Mohit; Liu, Shangxi; Carter, David E.; Abraham, David; Shi-Wen, Xu; Carreira, Patricia; Fontaine T, Benjamin A; Shea, Barry S; Tager, Andrew M; Leask, Andrew; Lamas, Santiago; Rodríguez-Pascual, Fernando

    2011-01-01

    Objective Enhanced adhesive signaling including activation of the focal adhesion kinase (FAK) is a hallmark of fibroblasts from lung fibrosis patients, and FAK has been therefore hypothesized to be a key mediator of this disease. This study was undertaken to characterize the contribution of FAK to the development of pulmonary fibrosis both in vivo and in vitro. Methods FAK expression and activity were analyzed in lung tissue samples from lung fibrosis patients by immunohistochemistry. Mice orally treated with the FAK inhibitor, PF-562,271, or with siRNA-mediated silencing of FAK, were exposed to intratracheally instilled bleomycin to induce lung fibrosis, and the lungs were harvested for histological and biochemical analysis. Using endothelin-1 (ET-1) as stimulus, cell adhesion and contraction, as well as profibrotic gene expression were studied in fibroblasts isolated from wild type and FAK-deficient mouse embryos. ET-1-mediated FAK activation and gene expression were studied in primary mouse lung fibroblasts, as well as in wild type and integrin β1-deficient fibroblasts. Results Increased FAK expression and activity are upregulated in fibroblast foci and remodeled vessels in lung fibrosis patients. Pharmacological or siRNA-mediated targeting of FAK resulted in marked abrogation of bleomycin-induced lung fibrosis. Loss of FAK impaired the acquisition of a profibrotic phenotype in response to ET-1. Profibrotic gene expression leading to myofibroblast differentiation required cell adhesion, and was driven by Jun N-terminal kinase activation through integrin β1/FAK signaling. Conclusion These results implicate FAK as a central mediator of fibrogenesis, and highlight this kinase as a potential therapeutic target in fibrotic diseases. PMID:22492165

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

    PubMed

    Piacentini, Enrique; Villagrá, Ana; López-Aguilar, Josefina; Blanch, Lluis

    2004-04-01

    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 healthy anesthetized patients and in patients ventilated with low positive end-expiratory pressure. However, it is unclear whether recruitment maneuvers are useful when patients with acute lung injury or acute respiratory distress syndrome are ventilated with high positive end-expiratory pressure, and in the presence of lung fibrosis or a stiff chest wall. Moreover, it is unclear whether the use of high airway pressures during recruitment maneuvers can cause bacterial translocation. This article reviews the intrinsic mechanisms of mechanical stress, the controversy regarding clinical use of recruitment maneuvers, and the interactions between lung infection and application of high intrathoracic pressures.

  13. Induction of interleukin-8 and interleukin-12 in neonatal ovine lung following experimental inoculation of bovine respiratory syncytial virus.

    PubMed

    Redondo, E; Gázquez, A; Vadillo, S; García, A; Franco, A; Masot, A J

    2014-05-01

    This study aimed to determine the immunohistochemical expression of interleukin (IL)-1β, tumour necrosis factor alpha (TNF)-α, interferon (IFN)-γ, IL-4, IL-6, IL-8, IL-10 and IL-12 and to measure the concentrations of these cytokines in lung tissue from lambs infected experimentally with bovine respiratory syncytial virus (BRSV). Lambs (n = 15) were inoculated at 2 days of age with 20 ml of viral inoculum (1.26 × 10(6) TCID50 per ml) or sterile medium (n = 15). Rectal temperature, pulse and respiratory rates were monitored daily in control and infected lambs. Lambs were killed and subject to necropsy examination at 1, 3, 5, 7 and 15 days post inoculation (dpi). There was a temporal association between pulmonary expression of these cytokines and lung pathology in BRSV-infected lambs. The cytokines IL-4 and IL-10 were not elevated, but there was a significant increase in IL-1β, TNF-α, IFN-γ and IL-6 proteins and labelled cells, suggesting that these cytokines may play a role in the biological response to BRSV infection and contribute to the development of lung lesions. There was also a significant increase in the cytokine concentration and number of immunolabelled cells expressing IL-8 and IL-12 in infected lungs, suggesting that these cytokines might be used as therapeutic targets in the management of BRSV, in conjunction with measures to combat the causative pathogen and prophylactic methods aimed at preventing infection.

  14. Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases

    SciTech Connect

    D.W. Nigg; Various Others

    2014-06-01

    BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25–76 ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung.

  15. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

    SciTech Connect

    Stambaugh, Cassandra; Nelms, Benjamin E.; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-09-15

    Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D{sub 99%}), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from

  16. Magnetic resonance imaging provides sensitive in vivo assessment of experimental ventilator-induced lung injury

    PubMed Central

    Kuethe, Dean O.; Filipczak, Piotr T.; Hix, Jeremy M.; Gigliotti, Andrew P.; Estépar, Raúl San José; Washko, George R.; Baron, Rebecca M.

    2016-01-01

    Animal models play a critical role in the study of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). One limitation has been the lack of a suitable method for serial assessment of acute lung injury (ALI) in vivo. In this study, we demonstrate the sensitivity of magnetic resonance imaging (MRI) to assess ALI in real time in rat models of VILI. Sprague-Dawley rats were untreated or treated with intratracheal lipopolysaccharide or PBS. After 48 h, animals were mechanically ventilated for up to 15 h to induce VILI. Free induction decay (FID)-projection images were made hourly. Image data were collected continuously for 30 min and divided into 13 phases of the ventilatory cycle to make cinematic images. Interleaved measurements of respiratory mechanics were performed using a flexiVent ventilator. The degree of lung infiltration was quantified in serial images throughout the progression or resolution of VILI. MRI detected VILI significantly earlier (3.8 ± 1.6 h) than it was detected by altered lung mechanics (9.5 ± 3.9 h, P = 0.0156). Animals with VILI had a significant increase in the Index of Infiltration (P = 0.0027), and early regional lung infiltrates detected by MRI correlated with edema and inflammatory lung injury on histopathology. We were also able to visualize and quantify regression of VILI in real time upon institution of protective mechanical ventilation. Magnetic resonance lung imaging can be utilized to investigate mechanisms underlying the development and propagation of ALI, and to test the therapeutic effects of new treatments and ventilator strategies on the resolution of ALI. PMID:27288491

  17. A recruitment breath manoeuvre directly after endotracheal suction improves lung function: An experimental study in pigs

    PubMed Central

    Kasim, Ihsan; Gulyas, Miklos; Almgren, Birgitta

    2009-01-01

    Background Atelectasis occurs after a well performed endotracheal suction. Clinical studies have shown that recruitment manoeuvres added after endotracheal suction during mechanical ventilation restore lung function. Repetitive lung over-distension is, however, harmful for the lung, and the effects of adding a larger breath, recruitment breath, directly after repeated endotracheal suction were therefore investigated. Methods Twelve healthy anaesthetized pigs were randomized into two groups: one without and one with a recruitment breath manoeuvre (RBM), i.e. a breath 15 cmH2O above inspiratory pressure for 10 s during pressure-controlled ventilation. The pigs were suctioned every hour for 4 hours with an open suction system. Results At the end of the study there was a statistically significant difference between the group given RBM and that without with respect to PaCO2, tidal volume (VT), and compliance (Crs). Without RBM, the PaCO2 increased from 4.6±0.4 to 6.1±1.5 kPa, VT decreased from 345±39 to 247±71 mL, and Crs decreased from 28±6 to 18±5 mL/cmH2O. There was no change in PaCO2 or Crs when a RBM was given. Morphological analysis revealed no differences in aeration of apical and central lung parenchyma. In the basal lung parenchyma there were, however, greater areas with normal lung parenchyma and less atelectasis after RBM. Conclusions Atelectasis created by endotracheal suction can be opened by inflating the lung for a short duration with low pressure, without over-distension, immediately after suction. PMID:19736601

  18. Changes in the biophysical properties and ultrastructure of lungs, and intrapulmonary fibrin deposition in experimental acute pancreatitis.

    PubMed Central

    Berry, A R; Davies, G C; Millar, A M; Taylor, T V

    1983-01-01

    Using an experimental model of acute pancreatitis in the rat, we have studied changes in the biophysical properties of lungs and intrapulmonary fibrin deposition in this condition. Acute pancreatitis is associated with a significant decrease in pulmonary compliance (p less than 0.01) and a significant increase in lung weight (p less than 0.01) compared with a control sham operation group. These changes are associated with a 24% increase in intrapulmonary 125I fibrinogen deposition (p less than 0.01), and an 18% increase in 125I fibrinogen deposition per gram of lung tissue (p less than 0.05) in acute pancreatitis, compared with a control sham operation group. The increased fibrinogen deposition is abolished by treatment with low dose heparin. Using the same animal model changes in pulmonary ultrastructure are shown using scanning electron microscopy. The results indicate that pulmonary abnormalities are associated with intrapulmonary fibrin deposition in experimental acute pancreatitis and these findings may be relevant to the well described respiratory complications of the condition in man. Images Fig. 3 Fig. 4 Fig. 7 PMID:6618271

  19. Effects of positive end-expiratory pressure titration and recruitment maneuver on lung inflammation and hyperinflation in experimental acid aspiration-induced lung injury.

    PubMed

    Ambrosio, Aline M; Luo, Rubin; Fantoni, Denise T; Gutierres, Claudia; Lu, Qin; Gu, Wen-Jie; Otsuki, Denise A; Malbouisson, Luiz M S; Auler, Jose O C; Rouby, Jean-Jacques

    2012-12-01

    In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

  20. Effect of positive end-expiratory pressure on acoustic wave propagation in experimental porcine lung injury.

    PubMed

    Räsänen, Jukka; Nemergut, Michael E; Gavriely, Noam

    2015-03-01

    To evaluate the effect of positive end-expiratory pressure (PEEP) on sound propagation through injured lungs, we injected a multifrequency broad-band sound signal into the airway of eight anesthetized, intubated and mechanically ventilated pigs, while recording transmitted sound at three locations bilaterally on the chest wall. Oleic acid injections effected a severe pulmonary oedema predominately in the dependent lung regions, with an average increase in venous admixture from 19 ± 15 to 59 ± 14% (P < 0.001), and a reduction in dynamic respiratory system compliance from 34 ± 7 to 14 ± 4 ml cmH2 O(-1) (P < 0.001). A concomitant decrease in sound transit time was seen in the dependent lung regions (P < 0.05); no statistically significant change occurred in the lateral or non-dependent areas. The application of PEEP resulted in a decrease in venous admixture, increase in respiratory system compliance and return of the sound transit time to pre-injury levels in the dependent lung regions. Our results indicate that sound transmission velocity increases in lung tissue affected by permeability-type pulmonary oedema in a manner reversible during alveolar recruitment with PEEP.

  1. The effect of pumpless extracorporeal CO2 removal on regional perfusion of the brain in experimental acute lung injury.

    PubMed

    Kreyer, Stefan; Muders, Thomas; Luepschen, Henning; Kricklies, Corinna; Linden, Katharina; Soehle, Martin; Zinserling, Joerg; Putensen, Christian; Wrigge, Hermann

    2013-07-01

    Lung-protective mechanical ventilation with low tidal volumes (V(T)) is often associated with hypercapnia (HC), which may be unacceptable in patients with brain injury. CO2 removal using a percutaneous extracorporeal lung assist (pECLA) enables normocapnia despite low V(T), but its effects on regional cerebral blood flow (rCBF) remain ambiguous. We hypothesized that reversal of HC by pECLA impairs rCBF in a porcine lung injury model. Lung injury was induced in 9 anesthetized pigs by hydrochloric acid aspiration. rCBF and systemic hemodynamics were measured by colored microsphere technique and transpulmonary-thermodilution during a randomized sequence of 4 experimental situations: pECLA shunt-on (1) with HC and (2) without HC, pECLA shunt-off (3) with HC and (4) without HC. HC increased rCBF (P<0.05). CO2 removal with pECLA resulting in normocapnia, decreased rCBF to levels comparable to those without pECLA and normocapnia. HC resulted in increased cardiac output (+25.5%). Cardiac output was highest during HC with pECLA shunt (+44.9%). During pECLA with CO2 removal, cardiac output (+38.1%) decreased compared with pECLA without CO2 removal, but stayed higher than during normocapnia/no pECLA shunt (P<0.05). In this animal model, mechanical ventilation with low V(T) was associated with HC and increased rCBF. CO2 removal by pECLA restored normocapnia, reduced rCBF to levels of normocapnia, but required a higher systemic blood flow for the perfusion of the pECLA device. If these results could be transferred to patients, extracorporeal CO2 removal might be an option for treatment of combined lung and brain injury in condition of a sufficient cardiac flow reserve.

  2. Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms

    PubMed Central

    2013-01-01

    Background Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector (Aah) and Androctonus amoreuxi (Aam). Results Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (β adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming. Conclusion These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom. PMID:23849182

  3. The Effects of Prone Position Ventilation on Experimental Mild Acute Lung Injury Induced by Intraperitoneal Lipopolysaccharide Injection in Rats.

    PubMed

    Bianchi, Aydra Mendes Almeida; Reboredo, Maycon Moura; Lucinda, Leda Marília Fonseca; Reis, Fernando Fonseca; Silva, Manfrinni Vinícius Alves; Rabelo, Maria Aparecida Esteves; Holanda, Marcelo Alcantara; Oliveira, Júlio César Abreu; Lorente, José Ángel; Pinheiro, Bruno do Valle

    2016-04-01

    The benefits of prone position ventilation are well demonstrated in the severe forms of acute respiratory distress syndrome, but not in the milder forms. We investigated the effects of prone position on arterial blood gases, lung inflammation, and histology in an experimental mild acute lung injury (ALI) model. ALI was induced in Wistar rats by intraperitoneal Escherichia coli lipopolysaccharide (LPS, 5 mg/kg). After 24 h, the animals with PaO2/FIO2 between 200 and 300 mmHg were randomized into 2 groups: prone position (n = 6) and supine position (n = 6). Both groups were compared with a control group (n = 5) that was ventilated in the supine position. All of the groups were ventilated for 1 h with volume-controlled ventilation mode (tidal volume = 6 ml/kg, respiratory rate = 80 breaths/min, positive end-expiratory pressure = 5 cmH2O, inspired oxygen fraction = 1) RESULTS: Significantly higher lung injury scores were observed in the LPS-supine group compared to the LPS-prone and control groups (0.32 ± 0.03; 0.17 ± 0.03 and 0.13 ± 0.04, respectively) (p < 0.001), mainly due to a higher neutrophil infiltration level in the interstitial space and more proteinaceous debris that filled the airspaces. Similar differences were observed when the gravity-dependent lung regions and non-dependent lung regions were analyzed separately (p < 0.05). The BAL neutrophil content was also higher in the LPS-supine group compared to the LPS-prone and control groups (p < 0.05). There were no significant differences in the wet/dry ratio and gas exchange levels. In this experimental extrapulmonary mild ALI model, prone position ventilation for 1 h, when compared with supine position ventilation, was associated with lower lung inflammation and injury.

  4. Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria.

    PubMed

    Souza, Mariana C; Silva, Johnatas D; Pádua, Tatiana A; Torres, Natália D; Antunes, Mariana A; Xisto, Debora G; Abreu, Thiago P; Capelozzi, Vera L; Morales, Marcelo M; Sá Pinheiro, Ana A; Caruso-Neves, Celso; Henriques, Maria G; Rocco, Patricia R M

    2015-05-22

    Malaria is the most relevant parasitic disease worldwide, and still accounts for 1 million deaths each year. Since current antimalarial drugs are unable to prevent death in severe cases, new therapeutic strategies have been developed. Mesenchymal stromal cells (MSC) confer host resistance against malaria; however, thus far, no study has evaluated the therapeutic effects of MSC therapy on brain and distal organ damage in experimental cerebral malaria. Forty C57BL/6 mice were injected intraperitoneally with 5 × 10(6) Plasmodium berghei-infected erythrocytes or saline. After 24 h, mice received saline or bone marrow (BM)-derived MSC (1x10(5)) intravenously and were housed individually in metabolic cages. After 4 days, lung and kidney morphofunction; cerebrum, spleen, and liver histology; and markers associated with inflammation, fibrogenesis, and epithelial and endothelial cell damage in lung tissue were analyzed. In P. berghei-infected mice, BM-MSCs: 1) reduced parasitemia and mortality; 2) increased phagocytic neutrophil content in brain, even though BM-MSCs did not affect the inflammatory process; 3) decreased malaria pigment detection in spleen, liver, and kidney; 4) reduced hepatocyte derangement, with an increased number of Kupffer cells; 5) decreased kidney damage, without effecting significant changes in serum creatinine levels or urinary flow; and 6) reduced neutrophil infiltration, interstitial edema, number of myofibroblasts within interstitial tissue, and collagen deposition in lungs, resulting in decreased lung static elastance. These morphological and functional changes were not associated with changes in levels of tumor necrosis factor-α, keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8), or interferon-γ, which remained increased and similar to those of P. berghei animals treated with saline. BM-MSCs increased hepatocyte growth factor but decreased VEGF in the P. berghei group. BM-MSC treatment increased survival and reduced

  5. Fractal Geometry Enables Classification of Different Lung Morphologies in a Model of Experimental Asthma

    NASA Astrophysics Data System (ADS)

    Obert, Martin; Hagner, Stefanie; Krombach, Gabriele A.; Inan, Selcuk; Renz, Harald

    2015-06-01

    Animal models represent the basis of our current understanding of the pathophysiology of asthma and are of central importance in the preclinical development of drug therapies. The characterization of irregular lung shapes is a major issue in radiological imaging of mice in these models. The aim of this study was to find out whether differences in lung morphology can be described by fractal geometry. Healthy and asthmatic mouse groups, before and after an acute asthma attack induced by methacholine, were studied. In vivo flat-panel-based high-resolution Computed Tomography (CT) was used for mice's thorax imaging. The digital image data of the mice's lungs were segmented from the surrounding tissue. After that, the lungs were divided by image gray-level thresholds into two additional subsets. One subset contained basically the air transporting bronchial system. The other subset corresponds mainly to the blood vessel system. We estimated the fractal dimension of all sets of the different mouse groups using the mass radius relation (mrr). We found that the air transporting subset of the bronchial lung tissue enables a complete and significant differentiation between all four mouse groups (mean D of control mice before methacholine treatment: 2.64 ± 0.06; after treatment: 2.76 ± 0.03; asthma mice before methacholine treatment: 2.37 ± 0.16; after treatment: 2.71 ± 0.03; p < 0.05). We conclude that the concept of fractal geometry allows a well-defined, quantitative numerical and objective differentiation of lung shapes — applicable most likely also in human asthma diagnostics.

  6. Fast Versus Slow Recruitment Maneuver at Different Degrees of Acute Lung Inflammation Induced by Experimental Sepsis.

    PubMed

    Santos, Raquel S; Moraes, Lillian; Samary, Cynthia S; Santos, Cíntia L; Ramos, Maíra B A; Vasconcellos, Ana P; Horta, Lucas F; Morales, Marcelo M; Capelozzi, Vera L; Garcia, Cristiane S N B; Marini, John J; Gama de Abreu, Marcelo; Pelosi, Paolo; Silva, Pedro L; Rocco, Patricia R M

    2016-04-01

    Large tidal volume (VT) breaths or "recruitment maneuvers" (RMs) are used commonly to open collapsed lungs, but their effectiveness may depend on how the RM is delivered. We hypothesized that a stepped approach to RM delivery ("slow" RM) compared with a nonstepped ("fast" RM), when followed by decremental positive end-expiratory pressure (PEEP) titration to lowest dynamic elastance, would (1) yield a more homogeneous inflation of the lungs, thus reducing the PEEP obtained during post-RM titration; (2) produce less lung morphofunctional injury, regardless of the severity of sepsis-induced acute lung inflammation; and (3) result in less biological damage in severe, but not in moderate, acute lung inflammation. Sepsis was induced by cecal ligation and puncture surgery in 51 Wistar rats. After 48 hours, animals were anesthetized, mechanically ventilated (VT = 6 mL/kg), and stratified by PO2/fraction of inspired oxygen ratio into moderate (≥300) and severe (<300) acute lung inflammation groups. Each group was then subdivided randomly into 3 subgroups: (1) nonrecruited; (2) RM with continuous positive airway pressure (30 cm H2O for 30 seconds; CPAPRM or fast RM); and (3) RM with stepwise airway pressure increase (5 cm H2O/step, 8.5 seconds/step, 6 steps, 51 seconds; STEPRM or slow RM), with a maximum pressure hold for 10 seconds. All animals underwent decremental PEEP titration to determine the level of PEEP required to optimize dynamic compliance after RM and were then ventilated for 60 minutes with VT = 6 mL/kg, respiratory rate = 80 bpm, fraction of inspired oxygen = 0.4, and the newly adjusted PEEP for each animal. Respiratory mechanics, hemodynamics, and arterial blood gases were measured before and at the end of 60-minute mechanical ventilation. Lung histology and biological markers of inflammation and damage inflicted to endothelial cells were evaluated at the end of the 60-minute mechanical ventilation. Respiratory system mean airway pressure was lower in

  7. Total deposition of ultrafine particles in the lungs of healthy men and women: experimental and theoretical results

    PubMed Central

    2016-01-01

    Background Inhaled ultrafine particles (UFP) may induce greater adverse respiratory effects than larger particles occurring in the ambient atmosphere. Due to this potential of UFP to act as triggers for diverse lung injuries medical as well as physical research has been increasingly focused on the exact deposition behavior of the particles in lungs of various probands. Main purpose of the present study was the presentation of experimental and theoretical data of total, regional, and local UFP deposition in the lungs of men and women. Methods Both experiments and theoretical simulations were carried out by using particle sizes of 0.04, 0.06, 0.08, and 0.10 µm [number median diameters (NMD)]. Inhalation of UFP took place by application of predefined tidal volumes (500, 750, and 1,000 mL) and respiratory flow rates (150, 250, 375, and 500 mL·s−1). For male subjects a functional residual capacity (FRC) of 3,911±892 mL was measured, whereas female probands had a FRC of 3,314±547 mL. Theoretical predictions were based on (I) a stochastic model of the tracheobronchial tree; (II) particle transport computations according to a random walk algorithm; and (III) empirical formulae for the description of UFP deposition. Results Total deposition fractions (TDF) are marked by a continuous diminution with increasing particle size. Whilst particles measuring 0.04 µm in size deposit in the respiratory tract by 40–70%, particles with a size of 0.10 µm exhibit deposition values ranging from 20% to 45%. Except for the largest particles studied here TDF of female probands are higher than those obtained for male probands. Differences between experimental and theoretical results are most significant for 0.10 µm particles, but never exceed 20%. Predictions of regional (extrathoracic, tracheobronchial, alveolar) UFP deposition show clearly that females tend to develop higher tracheobronchial and alveolar deposition fractions than males. This discrepancy is also confirmed by

  8. Total deposition of ultrafine particles in the lungs of healthy men and women: experimental and theoretical results.

    PubMed

    Sturm, Robert

    2016-06-01

    Inhaled ultrafine particles (UFP) may induce greater adverse respiratory effects than larger particles occurring in the ambient atmosphere. Due to this potential of UFP to act as triggers for diverse lung injuries medical as well as physical research has been increasingly focused on the exact deposition behavior of the particles in lungs of various probands. Main purpose of the present study was the presentation of experimental and theoretical data of total, regional, and local UFP deposition in the lungs of men and women. Both experiments and theoretical simulations were carried out by using particle sizes of 0.04, 0.06, 0.08, and 0.10 µm [number median diameters (NMD)]. Inhalation of UFP took place by application of predefined tidal volumes (500, 750, and 1,000 mL) and respiratory flow rates (150, 250, 375, and 500 mL·s(-1)). For male subjects a functional residual capacity (FRC) of 3,911±892 mL was measured, whereas female probands had a FRC of 3,314±547 mL. Theoretical predictions were based on (I) a stochastic model of the tracheobronchial tree; (II) particle transport computations according to a random walk algorithm; and (III) empirical formulae for the description of UFP deposition. Total deposition fractions (TDF) are marked by a continuous diminution with increasing particle size. Whilst particles measuring 0.04 µm in size deposit in the respiratory tract by 40-70%, particles with a size of 0.10 µm exhibit deposition values ranging from 20% to 45%. Except for the largest particles studied here TDF of female probands are higher than those obtained for male probands. Differences between experimental and theoretical results are most significant for 0.10 µm particles, but never exceed 20%. Predictions of regional (extrathoracic, tracheobronchial, alveolar) UFP deposition show clearly that females tend to develop higher tracheobronchial and alveolar deposition fractions than males. This discrepancy is also confirmed by airway generation

  9. Midterm effects of fluid resuscitation strategies in an experimental model of lung contusion and hemorrhagic shock.

    PubMed

    Prunet, Bertrand; Prat, Nicolas; Couret, David; Cordier, Pierre-Yves; De Bourmont, Sophie; Lambert, Dominique; Asencio, Yves; Meaudre, Eric; Michelet, Pierre

    2014-02-01

    This study compared three different fluid resuscitation strategies in terms of respiratory tolerance and hemodynamic efficacy in a pig model of blunt chest trauma with lung contusion and controlled hemorrhagic shock. We hypothesized that the choice of fluid resuscitation strategy (type and amount of fluids) may impact differently contused lungs in terms of extravascular lung water (EVLW) 20 h after trauma. Anesthetized female pigs (n = 5/group) received five bolt shots to the right thoracic cage and allowed to hemorrhage for 30 min, with 25 to 30 mL/kg of blood loss. Pigs were randomly assigned to resuscitation groups that maintained a minimum mean arterial blood pressure of 70 mmHg with one of three methods: normal saline (NS), unrestricted normal saline; NOREPI, low-volume normal saline with norepinephrine; or HS-HES, hypertonic saline with hydroxyethyl starch. Control pigs were anesthetized, but received no injury or treatment. After 20 h, animals were killed to measure EVLW by gravimetry. Fluid loading was significantly different in each group. All three treatment groups had higher EVLW than controls. Moderate, bilateral pulmonary edema was observed in the NS and HS-HES groups. The three treatment groups showed similar reductions in oxygenation. Static pulmonary compliance was diminished in the NS and HS-HES groups, but compliance was similar in NOREPI and control groups. The NOREPI group had pathological lactate levels. This study demonstrated the impact of fluid resuscitation on contused lungs. Twenty hours after the trauma, all three resuscitation approaches showed modest clinical consequences, with moderate lung edema and reduced compliance in response to the infused volume.

  10. Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension.

    PubMed

    Avouac, Jerome; Konstantinova, Irena; Guignabert, Christophe; Pezet, Sonia; Sadoine, Jeremy; Guilbert, Thomas; Cauvet, Anne; Tu, Ly; Luccarini, Jean-Michel; Junien, Jean-Louis; Broqua, Pierre; Allanore, Yannick

    2017-11-01

    To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH. Mice received two doses of IVA337 (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. IVA337 demonstrated at a dose of 100 mg/kg a marked protection from the development of lung fibrosis in both mouse models compared with mice receiving 30 mg/kg of IVA337 or vehicle. Histological score was markedly reduced by 61% in the bleomycin model and by 50% in Fra-2 transgenic mice, and total lung hydroxyproline concentrations decreased by 28% and 48%, respectively, as compared with vehicle-treated mice. IVA337 at 100 mg/kg also significantly decreased levels of fibrogenic markers in lesional lungs of both mouse models. In addition, IVA337 substantially alleviated PH in Fra-2 transgenic mice by improving haemodynamic measurements and vascular remodelling. In primary human lung fibroblasts, IVA337 inhibited in a dose-dependent manner fibroblast to myofibroblasts transition induced by TGF-β and fibroblast proliferation mediated by PDGF. We demonstrate that treatment with 100 mg/kg IVA337 prevents lung fibrosis in two complementary animal models and substantially attenuates PH in the Fra-2 mouse model. These findings confirm that the pan-PPAR agonist IVA337 is an appealing therapeutic candidate for these cardiopulmonary involvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. HIV Suppression Restores the Lung Mucosal CD4+ T-Cell Viral Immune Response and Resolves CD8+ T-Cell Alveolitis in Patients at Risk for HIV-Associated Chronic Obstructive Pulmonary Disease.

    PubMed

    Popescu, Iulia; Drummond, M Bradley; Gama, Lucio; Lambert, Allison; Hoji, Aki; Coon, Tiffany; Merlo, Christian A; Wise, Robert A; Keruly, Jeanne; Clements, Janice E; Kirk, Gregory D; McDyer, John F

    2016-11-15

    Lung CD4(+) T-cell depletion and dysfunction, CD8(+) T-cell alveolitis, smoking, and poor control of human immunodeficiency virus (HIV) are features of HIV-associated chronic obstructive pulmonary disease (COPD), but these changes have not been evaluated in smokers at risk for COPD. We evaluated the impact of viral suppression following initiation of antiretroviral therapy (ART) on HIV-specific immunity and the balance of the CD4(+) T-cell to CD8(+) T-cell ratio in the lung.  Using flow cytometry, we assessed the T-cell immune response in lung and blood specimens obtained from 12 actively smoking HIV-positive patients before ART initiation and after ART-associated viral suppression.  HIV suppression resulted in enhanced lung and systemic HIV-specific CD4(+) T-cell immune responses without significant changes in CD8(+) T-cell responses. We observed an increase in lung ratios of CD4(+) T cells to CD8(+) T cells and CD4(+) T-cell frequencies, decreased CD8(+) T-cell numbers, and resolution of CD8(+) T-cell alveolitis after ART in 9 of 12 individuals. Viral suppression reduced Fas receptor and programmed death 1 expression in lung CD4(+) T cells, correlating with enhanced effector function and reduced susceptibility to apoptosis. HIV suppression rescued peripheral but not lung HIV-specific CD4(+) T-cell proliferation, resulting in augmented effector multifunction.  Together, our results demonstrate that HIV suppression restores lung mucosal HIV-specific CD4(+) T-cell multifunctional immunity and balance in the ratio of CD4(+) T cells to CD8(+) T cells, often resolving CD8(+) T-cell alveolitis in active smokers. Peripheral expansion and redistribution of CD4(+) T cells and increased resistance to apoptosis are 2 mechanisms contributing to immunologic improvement following viral suppression in patients at risk for HIV-associated COPD. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For

  12. Experimental Investigation of Coronal Plasma Conditions in Direct-Drive ICF Using Time-Resolved X-Ray Spectroscopy

    NASA Astrophysics Data System (ADS)

    Sawada, H.; Regan, S. P.; Goncharov, V. N.; Knauer, J. P.; Epstein, R.; Craxton, R. S.; Delettrez, J. A.; Marshall, F. J.; Yaakobi, B.; Meyerhofer, D. D.; Radha, P. B.; Sangster, T. C.; Seka, W.

    2003-10-01

    The ne and Te of planar plasmas generated with six beams of the OMEGA laser are diagnosed with time-resolved K-shell spectroscopy of microdot tracer layers. Plastic foils (125 μm thick) with buried microdots (Al, KCl) were irradiated with a high-intensity, 100-ps Gaussian pulse (5 × 10^14 W/cm^2) or a low-intensity (3 × 10^13 W/cm^2), 1-ns square pulse, corresponding to the initial stages of direct-drive implosions with and without a short, high-intensity picket at the beginning of the drive pulse. The microdot buried depth was varied (0.1 to 0.5 μm) to probe the plasma at different times. Simulated spectra generated by post-processing hydrocode output (1-D LILAC, 2-D SAGE) with the FLY atomic physics code will be compared with the measured spectra. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460.

  13. Differential Cytokine Gene Expression in Granulomas from Lungs and Lymph Nodes of Cattle Experimentally Infected with Aerosolized Mycobacterium bovis

    PubMed Central

    2016-01-01

    The hallmark lesion of tuberculosis in humans and animals is the granuloma. The granuloma represents a distinct host cellular immune response composed of epithelioid macrophages, lymphocytes, and multinucleated giant cells, often surrounding a caseous necrotic core. Within the granuloma, host-pathogen interactions determine disease outcome. Factors within the granulomas such as cytokines and chemokines drive cell recruitment, activity, function and ultimately the success or failure of the host’s ability to control infection. Hence, an understanding of the granuloma-level cytokine response is necessary to understand tuberculosis pathogenesis. In-situ cytokine expression patterns were measured using a novel in situ hybridization assay, known as RNAScope® in granulomas of the lungs, tracheobronchial lymph nodes and caudal mediastinal lymph nodes of cattle experimentally infected with Mycobacterium bovis via aerosol exposure. In spite of microscopic morphological similarities, significant differences were seen between late stage granulomas of the lung compared to those of the tracheobronchial lymph nodes for IL-17A, IFN-γ, TGF-β, IL10 and IL-22 but not for TNF-α. Additionally, significant differences were noted between granulomas from two different thoracic lymph nodes that both receive afferent lymphatics from the lungs (i.e., tracheobronchial and caudal mediastinal lymph nodes) for TNF-α, IL-17A, IFN-γ, TGF-β and IL-10 but not for IL-22. These findings show that granuloma morphology alone is not a reliable indicator of granuloma function as granulomas of similar morphologies can have disparate cytokine expression patterns. Moreover, anatomically distinct lymph nodes (tracheobronchial vs caudal mediastinal) differ in cytokine expression patterns even when both receive afferent lymphatics from a lung containing tuberculoid granulomas. These findings show that selection of tissue and anatomic location are critical factors in assessing host immune response to M

  14. Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension.

    PubMed

    de Mendonça, Lucas; Felix, Nathane S; Blanco, Natália G; Da Silva, Jaqueline S; Ferreira, Tatiana P; Abreu, Soraia C; Cruz, Fernanda F; Rocha, Nazareth; Silva, Patrícia M; Martins, Vanessa; Capelozzi, Vera L; Zapata-Sudo, Gizele; Rocco, Patricia R M; Silva, Pedro L

    2017-10-03

    Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Twenty-eight Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, while a control group received saline (SAL) instead. On day 14, both groups were further randomized to receive 10(5) adipose-derived MSCs or SAL intravenously (n = 7/group). On day 28, right ventricular systolic pressure (RVSP) and the gene expression of mediators associated with apoptosis, inflammation, fibrosis, Smad-1 levels, cell proliferation, and endothelial-mesenchymal transition were determined. In addition, lung histology (smooth muscle cell proliferation and plexiform-like injuries), CD68(+) and CD163(+) macrophages, and plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were evaluated. In the PAH group, adipose-derived MSCs, compared to SAL, reduced mean RVSP (29 ± 1 vs 39 ± 2 mmHg, p < 0.001), lung tissue collagen fiber content, smooth muscle cell proliferation, CD68(+) macrophages, interleukin-6 expression, and the antiapoptotic mediators Bcl-2 and survivin. Conversely, expression of the proapoptotic mediator procaspase-3 and plasma VEGF increased, with no changes in PDGF. In the pulmonary artery, MSCs dampened the endothelial-mesenchymal transition. In MCT-induced PAH, MSC therapy reduced lung vascular remodeling, thus improving hemodynamics. These beneficial effects were associated with increased levels of proapoptotic markers, mesenchymal-to-endothelial transition, reduced cell proliferation markers, and inflammation

  15. An experimental model-based exploration of cytokines in ablative radiation-induced lung injury in vivo and in vitro.

    PubMed

    Hong, Zhen-Yu; Song, Kwang Hyun; Yoon, Joo-Heon; Cho, Jaeho; Story, Michael D

    2015-06-01

    Stereotactic ablative radiotherapy is a newly emerging radiotherapy treatment method that, compared with conventionally fractionated radiation therapy (CFRT), allows an ablative dose of radiation to be delivered to a confined area around a tumor. The aim of the present study was to investigate the changes of various cytokines that may be involved in ablative radiation-induced lung injury in vitro and in vivo. In the in vivo study, ablative-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal irradiator. The levels of 24 cytokines in the peripheral blood were tested at several time points after irradiation. For the in vitro study, three mouse cell types (type II pneumocytes, alveolar macrophages, and fibroblasts) known to play important roles in radiation-induced pneumonitis and lung fibrosis were analyzed using a co-culture system. In the in vivo study, we found obvious patterns of serum cytokine changes depending on the volume of tissue irradiated (2-mm vs. 3.5-mm collimator). Only the levels of 3 cytokines increased with the 2-mm collimator at the acute phase (1-2 weeks after irradiation), while the majority of cytokines were elevated with the 3.5-mm collimator. In the in vitro co-culture system, after the cells were given an ablative dose of irradiation, the levels of five cytokines (GM-CSF, G-CSF, IL-6, MCP-1, and KC) increased significantly in a dose-dependent manner. The cytokine levels in our radiation-induced lung injury model showed specific changes, both in vivo and in vitro. These results imply that biological studies related to ablative-dose small-volume irradiation should be investigated using the corresponding experimental models rather than on those simulating large-volume CFRT.

  16. Experimental chronic obstructive lung disease. I. Bronchopulmonary changes induced in rabbits by prolonged exposure to formaldehyde.

    PubMed

    Ionescu, J; Marinescu, D; Tapu, V; Eskenasy, A

    1978-01-01

    The prolonged exposure to formaldehyde induces in the rabbit lung reactional and dystrophic changes involving the intrapulmonary bronchi, the bronchioli and the lung tissue. These changes are represented by bronchial cell hyperplasia with hypermucigenesis, extrusion of bronchial cells, bronchiolar hypermucigenesis, parcellary squamous metaplasia or necrobiosis of epithelia, thickening of bronchial and bronchiolar walls by subepithelial cell accumulations, destruction of musculo-elastic structures with stenosis or ectasia; the vascular reactions are hyperhaemic and proliferative with an obstructive and fibrous tendency; the parenchymal lesions are atelectasias, intralobular emphysema, and cellular thickening of alveolar walls and interlobular areas. The acid phosphatase, Tween-60-esterase, naphthol-AS-D-acetate-esterase, proline-oxidase and hydroxyproline-2-epimerase activities are increasing, while the leucyl-aminopeptidase and beta-glucuronidase ones are decreasing. The qualitative observations are completed and sustained by quanitative studies of mucous cell kinetics, of cell accumulations and differentiations.

  17. Lung response after subchronic glass fiber intratracheal instillation: an experimental study on rats.

    PubMed

    Domokos-Hancu, Bianca; Man, Milena Adina; Liana, Hancu; Pop, Carmen Monica

    2014-03-01

    The aim of the study was to identify the effects on the lung after subchronic glass fiber intratracheal instillation study on rats. We evaluated the toxicological effects on the lung: persistent inflammatory reaction, cell proliferation, and pulmonary fibrosis on histopathological examination. We performed a glass fiber intratracheal instillation study on total 32 Wistar rats. The animals were divided into four groups: three test groups exposed to different doses of glass fiber and one control group. One week after the end of the exposure period, all animals were euthanized. The histopathological examination of the lung performed in this study followed both distribution of the lesions through the multilevel biopsies that were taken and the inflammatory profile using both hematoxilin-eozin and Sirius red staining. The inflammatory lesions described for the first group were minimal/slight (grade I) and the total score was between 0 and 10 points (mean value = 3). For the second group, the inflammatory lesions were moderate/marked (grade II) with discrete collagen proliferation and discrete fibrosis and the total score ranged between 11 and 20 points (mean value = 11,250). For the third group, the described inflammatory lesions were massive with total score ranging between 21 and 30 points with collagen deposition, pulmonary and pleural fibrosis, and lung emphysema (mean value = 21,750) and no lesion in control group (with statistically significant difference P ≤ .001). This study of fiber glass intratracheal instillation of three different doses demonstrates that exposure to fiber glass is responsible for the development of persistent inflammatory response and a large range of hystopathological lesions which correlate to the administered dose.

  18. Percutaneous Radiofrequency Lung Ablation Combined with Transbronchial Saline Injection: An Experimental Study in Swine

    SciTech Connect

    Kawai, T. Kaminou, T. Sugiura, K.; Hashimoto, M.; Ohuchi, Y.; Adachi, A.; Fujioka, S.; Ito, H.; Nakamura, K.; Ihaya, T.; Ogawa, T.

    2010-02-15

    To evaluate the efficacy of radiofrequency lung ablation with transbronchial saline injection. The bilateral lungs of eight living swine were used. A 13-gauge bone biopsy needle was inserted percutaneously into the lung, and 1 ml of muscle paste was injected to create a tumor mimic. In total, 21 nodules were ablated. In the saline injection group (group A), radiofrequency ablation (RFA) was performed for 11 nodules after transbronchial saline injection under balloon occlusion with a 2-cm active single internally cooled electrode. In the control group (group B), conventional RFA was performed for 10 nodules as a control. The infused saline liquid showed a wedge-shaped and homogeneous distribution surrounding a tumor mimic. All 21 RFAs were successfully completed. The total ablation time was significantly longer (13.4 {+-} 2.8 min vs. 8.9 {+-} 3.5 min; P = 0.0061) and the tissue impedance was significantly lower in group A compared with group B (73.1 {+-} 8.8 {Omega} vs. 100.6 {+-} 16.6 {Omega}; P = 0.0002). The temperature of the ablated area was not significantly different (69.4 {+-} 9.1{sup o}C vs. 66.0 {+-} 7.9{sup o}C; P = 0.4038). There was no significant difference of tumor mimic volume (769 {+-} 343 mm{sup 3} vs. 625 {+-} 191 mm{sup 3}; P = 0.2783). The volume of the coagulated area was significantly larger in group A than in group B (3886 {+-} 1247 mm{sup 3} vs. 2375 {+-} 1395 mm{sup 3}; P = 0.0221). Percutaneous radiofrequency lung ablation combined with transbronchial saline injection can create an extended area of ablation.

  19. Local lung deposition of ultrafine particles in healthy adults: experimental results and theoretical predictions

    PubMed Central

    2016-01-01

    Background Ultrafine particles (UFP) of biogenic and anthropogenic origin occur in high numbers in the ambient atmosphere. In addition, aerosols containing ultrafine powders are used for the inhalation therapy of various diseases. All these facts make it necessary to obtain comprehensive knowledge regarding the exact behavior of UFP in the respiratory tract. Methods Theoretical simulations of local UFP deposition are based on previously conducted inhalation experiments, where particles with various sizes (0.04, 0.06, 0.08, and 0.10 µm) were administered to the respiratory tract by application of the aerosol bolus technique. By the sequential change of the lung penetration depth of the inspired bolus, different volumetric lung regions could be generated and particle deposition in these regions could be evaluated. The model presented in this contribution adopted all parameters used in the experiments. Besides the obligatory comparison between practical and theoretical data, also advanced modeling predictions including the effect of varying functional residual capacity (FRC) and respiratory flow rate were conducted. Results Validation of the UFP deposition model shows that highest deposition fractions occur in those volumetric lung regions corresponding to the small and partly alveolated airways of the tracheobronchial tree. Particle deposition proximal to the trachea is increased in female probands with respect to male subjects. Decrease of both the FRC and the respiratory flow rate results in an enhancement of UFP deposition. Conclusions The study comes to the conclusion that deposition of UFP taken up via bolus inhalation is influenced by a multitude of factors, among which lung morphometry and breathing conditions play a superior role. PMID:27942511

  20. Local lung deposition of ultrafine particles in healthy adults: experimental results and theoretical predictions.

    PubMed

    Sturm, Robert

    2016-11-01

    Ultrafine particles (UFP) of biogenic and anthropogenic origin occur in high numbers in the ambient atmosphere. In addition, aerosols containing ultrafine powders are used for the inhalation therapy of various diseases. All these facts make it necessary to obtain comprehensive knowledge regarding the exact behavior of UFP in the respiratory tract. Theoretical simulations of local UFP deposition are based on previously conducted inhalation experiments, where particles with various sizes (0.04, 0.06, 0.08, and 0.10 µm) were administered to the respiratory tract by application of the aerosol bolus technique. By the sequential change of the lung penetration depth of the inspired bolus, different volumetric lung regions could be generated and particle deposition in these regions could be evaluated. The model presented in this contribution adopted all parameters used in the experiments. Besides the obligatory comparison between practical and theoretical data, also advanced modeling predictions including the effect of varying functional residual capacity (FRC) and respiratory flow rate were conducted. Validation of the UFP deposition model shows that highest deposition fractions occur in those volumetric lung regions corresponding to the small and partly alveolated airways of the tracheobronchial tree. Particle deposition proximal to the trachea is increased in female probands with respect to male subjects. Decrease of both the FRC and the respiratory flow rate results in an enhancement of UFP deposition. The study comes to the conclusion that deposition of UFP taken up via bolus inhalation is influenced by a multitude of factors, among which lung morphometry and breathing conditions play a superior role.

  1. Vagal Ischemia Induced Lung Immune Component Infarct Following Subarachnoid Hemorrhage: An Experimental Study.

    PubMed

    Atalay, Canan; Gundogdu, Betul; Aydin, Mehmet Dumlu

    2017-01-01

    Neurogenic pulmonary edema (NPE) is the most serious complication of subarachnoid hemorrhage (SAH). As vagal nerves have vital roles in lung functions, vagal ischemia may have a causative role in the pathogenesis of NPE. We examined whether there was a relationship between vagal complex ischemia and lung immune complexes occupying the lymph node infarct in SAH. Thirty-two rabbits were divided into three groups: Control (n=5), SHAM (n=5) and SAH group (n=22). SAH was created by autologous blood injection into the cisterna magna and followed-up for 3 weeks. Vasospasm index (VSI) was defined as the ratio of the lung lymph node arteries (LLNA) wall section (wall ring) surface to the lumen surface. Degenerated axon numbers of vagal nerves, neuron densities of the nodose ganglion (NG) and VSIs of LLNA were compared for all groups. The mean degenerated vagal nerve axon density, neuron density of NG, and VSI of LLNA were 26±8/mm < sup > 2 < /sup > , 30±5/mm < sup > 3 < /sup > , and 0.777±0.048 in the control group; 1300±100/mm2, 720±90/mm < sup > 3 < /sup > , and 1.148±0.090 in the animals with slight vasospasm (n=12); and 7300±530/mm < sup > 2 < /sup > , 5610±810/mm3, and 1.500±0.120 in the animals with severe vasospasm (n=10), respectively. Degenerated vagal axon and NG neuron density may be a causative factor in the development of LLNA vasospasm induced lymph node infarct in SAH. Lung lymph node infarct may be an important factor in the prognosis of NPE.

  2. Models for comparing lung-cancer risks in radon- and plutonium-exposed experimental animals

    SciTech Connect

    Gilbert, E.S.; Cross, F.T.; Sanders, C.L.; Dagle, G.E.

    1990-10-01

    Epidemiologic studies of radon-exposed underground miners have provided the primary basis for estimating human lung-cancer risks resulting from radon exposure. These studies are sometimes used to estimate lung-cancer risks resulting from exposure to other alpha- emitters as well. The latter use, often referred to as the dosimetric approach, is based on the assumption that a specified dose to the lung produces the same lung-tumor risk regardless of the substance producing the dose. At Pacific Northwest Laboratory, experiments have been conducted in which laboratory rodents have been given inhalation exposures to radon and to plutonium ({sup 239}PuO{sub 2}). These experiments offer a unique opportunity to compare risks, and thus to investigate the validity of the dosimetric approach. This comparison is made most effectively by modeling the age-specific risk as a function of dose in a way that is comparable to analyses of human data. Such modeling requires assumptions about whether tumors are the cause of death or whether they are found incidental to death from other causes. Results based on the assumption that tumors are fatal indicate that the radon and plutonium dose-response curves differ, with a linear function providing a good description of the radon data, and a pure quadratic function providing a good description of the plutonium data. However, results based on the assumption that tumors are incidental to death indicate that the dose-response curves for the two exposures are very similar, and thus support the dosimetric approach. 14 refs., 2 figs., 6 tabs.

  3. Effect of tramadol on lung injury induced by skeletal muscle ischemia-reperfusion: an experimental study*

    PubMed Central

    Takhtfooladi, Mohammad Ashrafzadeh; Jahanshahi, Amirali; Sotoudeh, Amir; Jahanshahi, Gholamreza; Takhtfooladi, Hamed Ashrafzadeh; Aslani, Kimia

    2013-01-01

    OBJECTIVE: To determine whether tramadol has a protective effect against lung injury induced by skeletal muscle ischemia-reperfusion. METHODS: Twenty Wistar male rats were allocated to one of two groups: ischemia-reperfusion (IR) and ischemia-reperfusion + tramadol (IR+T). The animals were anesthetized with intramuscular injections of ketamine and xylazine (50 mg/kg and 10 mg/kg, respectively). All of the animals underwent 2-h ischemia by occlusion of the femoral artery and 24-h reperfusion. Prior to the occlusion of the femoral artery, 250 IU heparin were administered via the jugular vein in order to prevent clotting. The rats in the IR+T group were treated with tramadol (20 mg/kg i.v.) immediately before reperfusion. After the reperfusion period, the animals were euthanized with pentobarbital (300 mg/kg i.p.), the lungs were carefully removed, and specimens were properly prepared for histopathological and biochemical studies. RESULTS: Myeloperoxidase activity and nitric oxide levels were significantly higher in the IR group than in the IR+T group (p = 0.001 for both). Histological abnormalities, such as intra-alveolar edema, intra-alveolar hemorrhage, and neutrophil infiltration, were significantly more common in the IR group than in the IR+T group. CONCLUSIONS: On the basis of our histological and biochemical findings, we conclude that tramadol prevents lung tissue injury after skeletal muscle ischemia-reperfusion. PMID:24068264

  4. Exogenous Hydrogen Sulfide (H2S) Protects Alveolar Growth in Experimental O2-Induced Neonatal Lung Injury

    PubMed Central

    Vadivel, Arul; Alphonse, Rajesh S.; Ionescu, Lavinia; Machado, Desiree S.; O’Reilly, Megan; Eaton, Farah; Haromy, Al; Michelakis, Evangelos D.; Thébaud, Bernard

    2014-01-01

    Background Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT). Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S), carbon monoxide and nitric oxide (NO), belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD. Methods We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate) to study its lung protective potential in vitro and in vivo. Results In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation. Conclusions H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT. PMID:24603989

  5. The effect of activated alveolar macrophages on experimental lung emphysema development. II. The study of fibroblast and alveolar macrophage co-culture.

    PubMed

    Sulkowska, M; Wołczyński, S; Sulkowski, S; Sobaniec-Lotowska, M; Chyczewski, L; Sulik, M; Kulikowski, M; Dziecioł, J; Berger, W

    1995-01-01

    The cell-cell interaction between fibroblasts and alveolar macrophages was examined using a co-culture system. Alveolar macrophages (AM) were harvested from the bronchoalveolar lavages (BAL) of rats with papain induced lung emphysema. The BCG-vaccine was applied as a macrophage mobilizing and activating agent. The morphological examinations carried out in scanning electron microscope (SEM) as well as the evaluation of the uptake of 3H-thymidine did not show any significant differences between respective co-cultures of fibroblasts and AM isolated both from the lungs of control and experimental animals (treated with BCG or papain, and BCG+papain). However, significant growth were noted in 3H-thymidine uptake between fibroblast cultures done with or without cells isolated from the lungs. The results obtained suggest that AM can promote fibroblast proliferation during the progression of experimental lung emphysema.

  6. Respiratory compliance but not gas exchange correlates with changes in lung aeration after a recruitment maneuver: an experimental study in pigs with saline lavage lung injury

    PubMed Central

    Henzler, Dietrich; Pelosi, Paolo; Dembinski, Rolf; Ullmann, Annette; Mahnken, Andreas H; Rossaint, Rolf; Kuhlen, Ralf

    2005-01-01

    Introduction Atelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchange Methods In eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH2O for 40 s with a constant positive end-expiratory pressure of 10 cmH2O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung. Results Nonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve

  7. The complete, temperature resolved experimental spectrum of methanol (CH{sub 3}OH) between 560 and 654 GHz

    SciTech Connect

    Fortman, Sarah M.; Neese, Christopher F.; De Lucia, Frank C.

    2014-02-20

    The complete spectrum of methanol (CH{sub 3}OH) has been characterized over a range of astrophysically significant temperatures in the 560.4-654.0 GHz spectral region. Absolute intensity calibration and analysis of 166 experimental spectra recorded over a slow 248-398 K temperature ramp provide a means for the simulation of the complete spectrum of methanol as a function of temperature. These results include contributions from v{sub t} = 3 and other higher states that are difficult to model via quantum mechanical (QM) techniques. They also contain contributions from the {sup 13}C isotopologue in terrestrial abundance. In contrast to our earlier work on semi-rigid species, such as ethyl cyanide and vinyl cyanide, significant intensity differences between these experimental values and those calculated by QM methods were found for many of the lines. Analysis of these differences shows the difficulty of the calculation of dipole matrix elements in the context of the internal rotation of the methanol molecule. These results are used to both provide catalogs in the usual line frequency, linestrength, and lower state energy format, as well as in a frequency point-by-point catalog that is particularly well suited for the characterization of blended lines.

  8. An experimental study of the recovery of injured porcine lungs with prolonged normothermic cellular ex vivo lung perfusion following donation after circulatory death.

    PubMed

    Spratt, John R; Mattison, Lars M; Iaizzo, Paul A; Brown, Roland Z; Helms, Haylie; Iles, Tinen L; Howard, Brian; Panoskaltsis-Mortari, Angela; Loor, Gabriel

    2017-09-01

    Donation after circulatory death (DCD) is an underused source of donor lungs. Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving standard donor lungs but may also be useful in the preservation and assessment of DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm ischemia and postmortem ventilation on graft recovery were evaluated. Adult male swine underwent general anesthesia and heparinization. In the control group (n = 4), cardioplegic arrest was induced and the lungs were procured immediately. In the four treatment groups, a period of agonal hypoxia was followed by either 1 h of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on EVLP were worse in all DCD lungs compared with controls. Hemodynamics and compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated impaired oxygenation. Normothermic cellular EVLP is effective in preserving and monitoring of DCD lungs. Early donor postmortem ventilation and timely procurement lead to improved graft function. © 2017 Steunstichting ESOT.

  9. Experimental induction of lung damage in the f344 rat upon exposure to citral, retinoic Acid (atra), ovalbumin and mold spores.

    PubMed

    Farah, Ibrahim O; Holt Gray, Carlene; Cameron, Joseph A; Tucci, Michelle A; Cason, Zelma; Benghuzzi, Hamed A

    2014-01-01

    The experimental impact of retinoic acid (All Trans Retinoic Acid; ATRA), citrals, ovalbumin and mold spores in the development of lung pathology and tissue remodeling are not well established in the literature. As well, the role of these agents in lung pathology was not ascertained under an in vivo setting. Therefore, it is hypothesized that citrals, ATRA, ovalbumin and mold-spore exposure will sensitize lung tissues and will lead to the development of lung tissue pathology in these animals. The study used an IACUC approved between-subject in vivo randomized split plot factorial design (F344 rat model; N=30). Mold spores were applied to animals by intra-tracheal route whereas vehicle, ovalbumin, C1, C2 and ATRA were administered by intra-peritoneal route. Rat weight data and blood were collected on Days 1 and 21. All animals were sacrificed on day 21 and lung tissues were processed for histopathology. Evidence from weights and blood (ANOVA and Duncan) as well as histopatholgical analysis supported the findings that exposure of these animals to C1, C2, ATRA, ovalbumin and mold spores showed different levels of lung tissue damage representing environmental exposure to these agents. This promising study showed variable lung tissue responses to the administration of ATRA, ovalbumin, citrals, and mold spores in the development of various levels of lung tissue pathologies.

  10. An experimental setup for high resolution 10.5 eV laser-based angle-resolved photoelectron spectroscopy using a time-of-flight electron analyzer.

    PubMed

    Berntsen, M H; Götberg, O; Tjernberg, O

    2011-09-01

    We present an experimental setup for laser-based angle-resolved time-of-flight photoemission. Using a picosecond pulsed laser, photons of energy 10.5 eV are generated through higher harmonic generation in xenon. The high repetition rate of the light source, variable between 0.2 and 8 MHz, enables high photoelectron count rates and short acquisition times. By using a time-of-flight analyzer with angle-resolving capabilities, electrons emitted from the sample within a circular cone of up to ±15° can be collected. Hence, simultaneous acquisition of photoemission data for a complete area of the Brillouin zone is possible. The current photon energy enables bulk sensitive measurements, high angular resolution, and the resulting covered momentum space is large enough to enclose the entire Brillouin zone in cuprate high-T(c) superconductors. Fermi edge measurements on polycrystalline Au shows an energy resolution better than 5 meV. Data from a test measurement of the Au(111) surface state are presented along with measurements of the Fermi surface of the high-T(c) superconductor Bi(2)Sr(2)CaCu(2)O(8 + δ) (Bi2212).

  11. Antitumor effects of two bisdioxopiperazines against two experimental lung cancer models in vivo

    PubMed Central

    Lu, Da-Yong; Xu, Bin; Ding, Jian

    2004-01-01

    Background Probimane (Pro), an anti-cancer agent originating in China, was derived from razoxane (ICRF-159, Raz), a drug created in Britain, specifically targeting at cancer metastasis and as a cardioprotectant of anthrocyclines. Pro and Raz are bisdioxopiperazine compounds. In this work, we evaluated the anti-tumor and anti-metastatic effects of Pro and Raz in vivo against two lung tumor models, one of murine origin (Lewis lung carcinoma, LLC) and one of human origin (LAX-83). Results After determining the lethal dosage of Pro and Raz, we assessed and compared the inhibitory effects of Pro and Raz against primary tumor growth and metastatic occurrences of LLC at the dosage of LD5. Pro and Raz were active against primary tumor growth and significantly inhibited pulmonary metastasis of LLC at same dose-ranges (inhibitory rates > 90 %). Both Raz and Pro were effective in 1, 5, and 9 day administration schedules. Three different schedules of Raz and Pro were effective against the primary tumor growth of LLC (35–50 %). The synergistic anticancer effect of Raz with bleomycin (Ble) (from 41.3 % to 73.3 %) was more obvious than those with daunorubicin (Dau) (from 33.1 % to 56.3 %) in the LLC tumor model. Pro was also seen to have synergistic anti-cancer effects with Ble in the LLC model. Both Raz and Pro inhibited the growth of LAX 83 in a statistically significant manner. Conclusions These data suggest that both Raz and Pro may have anti-tumor potentiality and Raz and Pro have combinative effects with Ble or Dau. The potential targets of bisdioxopiperazines may include lung cancers, especially on tumor metastasis. The anti-cancer effects of Raz and Pro can be increased with the help of other anticancer drugs. PMID:15617579

  12. Impact of Bacillus Calmette-Guérin Moreau vaccine on lung remodeling in experimental asthma.

    PubMed

    Samary, Cynthia dos Santos; Antunes, Mariana Alves; Silva, Johnatas Dutra; Silva, Adriana Lopes da; Araújo, Carla Cristina de; Bakker-Abreu, Ilka; Diaz, Bruno Lourenço; Fernezlian, Sandra; Parra, Edwin Roger; Capelozzi, Vera Luiza; Silva, Pedro Leme; Lapa e Silva, José Roberto; Rocco, Patricia Rieken Macedo

    2013-12-01

    We analyzed the effects of different administration routes and application times of the BCG-Moreau strain on airway and lung inflammation and remodeling in a murine model of allergic asthma. BALB/c mice (n=168) were divided into two groups. The first group received BCG-Moreau strain while the second group received saline using the same protocol. BCG or saline were intradermally or intranasally injected one or two months before the induction of asthma. Mice were further sensitized and challenged with ovalbumin or received saline. Twenty-four hours after the last challenge, BCG prevented the triggering of pro-inflammatory cytokines, probably by increasing Foxp3 and interleukin (IL)-10, modulating eosinophil infiltration and collagen fiber deposition, thus reducing airway hyperresponsiveness. In conclusion, BCG-Moreau prevented lung remodeling in the present model of allergic asthma, regardless of administration route and time of vaccination. These beneficial effects may be related to the increase in regulatory T cells and to IL-10 production in tandem with decreased Th2 cytokines (IL-4, IL-5, and IL-13).

  13. Gas transport efficacy of gills, lungs and skin: theory and experimental data.

    PubMed

    Piiper, J; Scheid, P

    1975-03-01

    The general functional principles encountered in respiratory organs of vertebrates are investigated. Generally three steps are involved in external gas exchange in vertebrates: (1) convective transport by flow of external respiratory medium, air or water (=ventilation); (2) transfer of gas between external respiratory medium and blood by diffusion (=medium/blood transfer); (3) convective transport by blood flow (=perfusion). According to the arrangement of external medium flow relative to capillary blood flow four construction principles may be distinguished: (a) counter-current system (fish gills), (b) cross-current system (avian lungs), (c) ventilated pool system (mammalian lungs), and (d) infinite pool system (amphibian skin). The gas transfer performance of these systems is analyzed in terms of conductances, relative partial pressure differences and limitations attributable to ventilation. to medium/blood transfer and to perfusion. The theory is applied to analysis of gas exchange data obtained in an elasmobranch fish, domestic fowl, dog and a lungless salamander. The analysis shows that, despite distinct differences in maximum efficiencies of these systems, the differences in efficiency values actually attained are much less pronounced, and may be even less marked when taking functional inhomogeneities into account which are neglected in this study.

  14. THE COMPLETE, TEMPERATURE-RESOLVED EXPERIMENTAL SPECTRUM OF VINYL CYANIDE (H{sub 2}CCHCN) BETWEEN 210 AND 270 GHz

    SciTech Connect

    Fortman, Sarah M.; Neese, Christopher F.; De Lucia, Frank C.; Medvedev, Ivan R.

    2011-08-10

    The results of an experimental approach to the identification and characterization of the astrophysical weed vinyl cyanide in the 210-270 GHz region are reported. This approach is based on spectrally complete, intensity-calibrated spectra taken at more than 400 different temperatures in the 210-270 GHz region and is used to produce catalogs in the usual astrophysical format: line frequency, line strength, and lower state energy. As in our earlier study of ethyl cyanide, we also include the results of a frequency point-by-point analysis, which is especially well suited for characterizing weak lines and blended lines in crowded spectra. This study shows substantial incompleteness in the quantum-mechanical (QM) models used to calculate astrophysical catalogs, primarily due to their omission of many low-lying vibrational states of vinyl cyanide, but also due to the exclusion of perturbed rotational transitions. Unlike ethyl cyanide, the QM catalogs for vinyl cyanide include analyses of perturbed excited vibrational states, whose modeling is more challenging. Accordingly, we include an empirical study of the frequency accuracy of these QM models. We observe modest frequency differences for some vibrationally excited lines.

  15. Unexpandable lung.

    PubMed

    Pereyra, Marco F; Ferreiro, Lucía; Valdés, Luis

    2013-02-01

    Unexpandable lung is a mechanical complication by which the lung does not expand to the chest wall, impeding a normal apposition between the two pleural layers. The main mechanism involved is the restriction of the visceral pleura due to the formation of a fibrous layer along this pleural membrane. This happens because of the presence of an active pleural disease (lung entrapment), which can be resolved if proper therapeutic measures are taken, or a remote disease (trapped lung), in which an irreversible fibrous pleural layer has been formed. The clinical suspicion arises with the presence of post-thoracocentesis hydropneumothorax or a pleural effusion that cannot be drained due to the appearance of thoracic pain. The diagnosis is based on the analysis of the pleural liquid, the determination of pleural pressures as we drain the effusion and on air-contrast chest CT. As both represent the continuity of one same process, the results will depend on the time at which these procedures are done. If, when given a lung that is becoming entrapped, the necessary therapeutic measures are not taken, the final result will be a trapped lung. In this instance, most patients are asymptomatic or have mild exertional dyspnea and therefore they do not require treatment. Nevertheless, in cases of incapacitating dyspnea, it may be necessary to use pleural decortication in order to resolve the symptoms. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

  16. RESOLVE Project

    NASA Technical Reports Server (NTRS)

    Parker, Ray; Coan, Mary; Cryderman, Kate; Captain, Janine

    2013-01-01

    The RESOLVE project is a lunar prospecting mission whose primary goal is to characterize water and other volatiles in lunar regolith. The Lunar Advanced Volatiles Analysis (LAVA) subsystem is comprised of a fluid subsystem that transports flow to the gas chromatograph - mass spectrometer (GC-MS) instruments that characterize volatiles and the Water Droplet Demonstration (WDD) that will capture and display water condensation in the gas stream. The LAVA Engineering Test Unit (ETU) is undergoing risk reduction testing this summer and fall within a vacuum chamber to understand and characterize component and integrated system performance. Testing of line heaters, printed circuit heaters, pressure transducers, temperature sensors, regulators, and valves in atmospheric and vacuum environments was done. Test procedures were developed to guide experimental tests and test reports to analyze and draw conclusions from the data. In addition, knowledge and experience was gained with preparing a vacuum chamber with fluid and electrical connections. Further testing will include integrated testing of the fluid subsystem with the gas supply system, near-infrared spectrometer, WDD, Sample Delivery System, and GC-MS in the vacuum chamber. This testing will provide hands-on exposure to a flight forward spaceflight subsystem, the processes associated with testing equipment in a vacuum chamber, and experience working in a laboratory setting. Examples of specific analysis conducted include: pneumatic analysis to calculate the WDD's efficiency at extracting water vapor from the gas stream to form condensation; thermal analysis of the conduction and radiation along a line connecting two thermal masses; and proportional-integral-derivative (PID) heater control analysis. Since LAVA is a scientific subsystem, the near-infrared spectrometer and GC-MS instruments will be tested during the ETU testing phase.

  17. Synthetic Triterpenoids Can Protect Against Toxicity Without Reducing the Efficacy of Treatment with Carboplatin and Paclitaxel in Experimental Lung Cancer

    PubMed Central

    Liby, Karen T.

    2014-01-01

    Synthetic oleanane triterpenoids are multifunctional drugs being developed for the prevention and treatment of a variety of chronic diseases driven by inflammation and oxidative stress. Low nanomolar concentrations of triterpenoids inhibit the induction of inflammatory cytokines, and these drugs are potent activators of the Nrf2 cytoprotective pathway. In contrast, low micromolar concentrations of triterpenoids increased the production of ROS and induced apoptosis in a dose-dependent manner in malignant MCF10 CA1a breast cancer cells. Because cancer cells respond differently to ROS than normal cells, it should be possible to exploit these differences therapeutically. In an experimental model of lung cancer, the triterpenoids activated the Nrf2 pathway, as seen by induction of the cytoprotective enzyme NQO1, and reduced the toxicity of carboplatin and paclitaxel. The induction of the Nrf2 pathway in the lung did not suppress the efficacy of treatment with carboplatin and paclitaxel, as the average tumor burden in the group treated with the combination of CDDO-Me and carboplatin/paclitaxel decreased by 90% (P < 0.05 vs. the controls and both single treatment groups). Understanding the dose response of triterpenoids and related drugs will help provide the proper context for optimizing their potential clinical utility. PMID:24659938

  18. Embryonic lung morphogenesis in organ culture: experimental evidence for a proteoglycan function in the extracellular matrix

    NASA Technical Reports Server (NTRS)

    Spooner, B. S.; Bassett, K. E.; Spooner, B. S. Jr

    1993-01-01

    The lung rudiment, isolated from mid-gestation (11 day) mouse embryos, can undergo morphogenesis in organ culture. Observation of living rudiments, in culture, reveals both growth and ongoing bronchiolar branching activity. To detect proteoglycan (PG) biosynthesis, and deposition in the extracellular matrix, rudiments were metabolically labeled with radioactive sulfate, then fixed, embedded, sectioned and processed for autoradiography. The sulfated glycosaminoglycan (GAG) types, composing the carbohydrate component of the proteoglycans, were evaluated by selective GAG degradative approaches that showed chondroitin sulfate PG principally associated with the interstitial matrix, and heparan sulfate PG principally associated with the basement membrane. Experiments using the proteoglycan biosynthesis disrupter, beta-xyloside, suggest that when chondroitin sulfate PG deposition into the ECM is perturbed, branching morphogenesis is compromised.

  19. Lung Radiofrequency Ablation: In Vivo Experimental Study with Low-Perfusion-Rate Multitined Electrodes

    SciTech Connect

    Crocetti, Laura Lencioni, Riccardo; Bozzi, Elena; Sbrana, Alberto; Bartolozzi, Carlo

    2008-05-15

    The purpose of this study was to investigate the feasibility and safety of lung radiofrequency (RF) ablation by using low-perfusion-rate, expandable, multitined electrodes in an in vivo animal model. Ten New Zealand White rabbits underwent RF ablation using low-perfusion-rate, expandable, multitined electrodes (Starburst Talon; RITA Medical Systems, Mountain View, CA) and a 200-W RF generator. The electrode was positioned under fluoroscopy guidance and a single percutaneous RF ablation was performed. Saline perfusate was doped with nonionic iodinated contrast agent to render it visible on computed tomography (CT). The pump infused the saline doped with contrast agent into the lateral tines at a rate of 0.1ml/min. The planned ablation was of 3 min, with the hooks deployed to 2 cm at a target temperature of 105{sup o}C. An immediate posttreatment CT scan documented the distribution of the doped saline and the presence of immediate complications. The animals were monitored for delayed complications and sacrificed within 72 h (n = 4), 2 weeks (n = 3), or 4 weeks (n = 3). Assessment of ablation zone and adjacent structures was done at autopsy. Major complications consisted of pneumothorax requiring drainage (n = 2) and skin burn (n = 1). Immediately after the procedure the area of ablation was depicted at CT as a round, well-demarcated area, homogeneously opacified by iodinated contrast medium (mean size, 2.3 {+-} 0.8 cm). The presence of a sharply demarcated area of coagulation necrosis (mean size, 2.1 {+-} 0.4 cm) without severe damage to adjacent structures was confirmed at autopsy. In one case, euthanized at 4 weeks, in whom pneumothorax and pleural effusion were depicted, pleural fibrinous adhesions were demonstrated at autopsy. In conclusion, lung RF ablation performed in an in vivo animal model using low-perfusion-rate, expandable, multitined electrodes is feasible and safe. No severe damage to adjacent structures was demonstrated.

  20. Bilateral vagotomy or atropine pre-treatment reduces experimental diesel-soot induced lung inflammation

    SciTech Connect

    McQueen, D.S. . E-mail: D.S.McQueen@ed.ac.uk; Donaldson, K.; McNeilly, J.D.; Barton, N.J.; Duffin, R.

    2007-02-15

    To investigate the role of the vagus nerve in acute inflammatory and cardiorespiratory responses to diesel particulate (DP) in the rat airway, we measured changes in respiration, blood pressure and neutrophils in lungs of urethane anesthetized Wistar rats 6-h post-instillation of DP (500 {mu}g) and studied the effect of mid-cervical vagotomy or atropine (1 mg kg{sup -1}) pre-treatment. In conscious rats, we investigated DP, with and without atropine pre-treatment. DP increased neutrophil level in BAL (bronchoalveolar lavage) fluid from intact anesthetized rats to 2.5 {+-} 0.7 x 10{sup 6} cells (n = 8), compared with saline instillation (0.3 {+-} 0.1 x 10{sup 6}, n = 7; P < 0.05). Vagotomy reduced DP neutrophilia to 0.8 {+-} 0.2 x 10{sup 6} cells (n = 8; P < 0.05 vs. intact); atropine reduced DP-induced neutrophilia to 0.3 {+-} 0.2 x 10{sup 6} (n = 4; P < 0.05). In conscious rats, DP neutrophilia of 8.5 {+-} 1.8 x 10{sup 6}, n = 4, was reduced by pre-treatment with atropine to 2.2 {+-} 1.2 x 10{sup 6} cells, n = 3. Hyperventilation occurred 6 h after DP in anesthetized rats with intact vagi, but not in bilaterally vagotomized or atropine pre-treated animals and was abolished by vagotomy (P < 0.05, paired test). There were no significant differences in the other variables (mean blood pressure, heart rate and heart rate variability) measured before and 360 min after DP. In conclusion, DP activates a pro-inflammatory vago-vagal reflex which is reduced by atropine. Muscarinic ACh receptors in the rat lung are involved in DP-induced neutrophilia, and hence muscarinic antagonists may reduce airway and/or cardiovascular inflammation evoked by inhaled atmospheric DP in susceptible individuals.

  1. Thermal Ablation of Lung Tissue: In Vivo Experimental Comparison of Microwave and Radiofrequency

    SciTech Connect

    Crocetti, Laura Bozzi, Elena; Faviana, Pinuccia; Cioni, Dania; Della Pina, Clotilde; Sbrana, Alberto; Fontanini, Gabriella; Lencioni, Riccardo

    2010-08-15

    This study was designed to compare feasibility, safety, and effectiveness of microwave (MW) ablation versus radiofrequency (RF) ablation of lung tissue in a rabbit model. Twenty New Zealand White rabbits were submitted to MW (n = 10, group A) or RF ablation (n = 10, group B). The procedures were performed with a prototype MW ablation device with a 1.6-cm radiating section antenna (Valleylab MW Ablation System) and with a 2-cm exposed-tip RF electrode (Cool-tip RF Ablation System). At immediate computed tomography increase in density, maximum diameters (D1-D3) of ablation zones were measured and ablation volume was calculated. Histopathologic assessment was performed 3 and 7 days after the procedure. Technical success was achieved in nine of 10 rabbits in each group. One death occurred in group B. Complications included pneumothorax (group A, n = 4; group B, n = 4), abscess (group A, n = 1; group B, n = 1), and thoracic wall burn (group A, n = 4). No significant differences were demonstrated in attenuation increase (P = 0.73), dimensions (P = 0.28, 0.86, 0.06, respectively, comparing D1-D3) and volume (P = 0.17). At histopathology, ablation zones were similar, with septal necrosis, edema, hemorrhage, and peripheral lymphocytic infiltrate. Complete thrombosis of more than 90% of vessels up to 2 mm in diameter was depicted at the periphery of the ablation zone in group A specimens. In group B specimens, complete thrombosis was depicted in 20% of vessels. Feasibility and safety of MW and RF ablation are similar in a lung rabbit model. MW ablation produces a greater damage to peripheral small vessels inducing thrombosis.

  2. The Effects of Short-Term Propofol and Dexmedetomidine on Lung Mechanics, Histology, and Biological Markers in Experimental Obesity.

    PubMed

    Heil, Luciana Boavista Barros; Santos, Cíntia L; Santos, Raquel S; Samary, Cynthia S; Cavalcanti, Vinicius C M; Araújo, Mariana M P N; Poggio, Hananda; Maia, Lígia de A; Trevenzoli, Isis Hara; Pelosi, Paolo; Fernandes, Fatima C; Villela, Nivaldo R; Silva, Pedro L; Rocco, Patricia R M

    2016-04-01

    Administering anesthetics to the obese population requires caution because of a variety of reasons including possible interactions with the inflammatory process observed in obese patients. Propofol and dexmedetomidine have protective effects on pulmonary function and are widely used in short- and long-term sedation, particularly in intensive care unit settings in lean and obese subjects. However, the functional and biological effects of these drugs in obesity require further elucidation. In a model of diet-induced obesity, we compared the short-term effects of dexmedetomidine versus propofol on lung mechanics and histology, as well as biological markers of inflammation and oxidative stress modulation in obesity. Wistar rats (n = 56) were randomly fed a standard diet (lean) or experimental diet (obese) for 12 weeks. After this period, obese animals received sodium thiopental intraperitoneally and were randomly allocated into 4 subgroups: (1) nonventilated (n = 4) for molecular biology analysis only (control); (2) sodium thiopental (n = 8); (3) propofol (n = 8); and (4) dexmedetomidine (n = 8), which received continuous IV administration of the corresponding agents and were mechanically ventilated (tidal volume = 6 mL/kg body weight, fraction of inspired oxygen = 0.4, positive end-expiratory pressure = 3 cm H2O) for 1 hour. Compared with lean animals, obese rats did not present increased body weight but had higher total body and trunk fat percentages, airway resistance, and interleukin-6 levels in the lung tissue (P = 0.02, P = 0.0027, and P = 0.01, respectively). In obese rats, propofol, but not dexmedetomidine, yielded increased airway resistance, bronchoconstriction index (P = 0.016, P = 0.02, respectively), tumor necrosis factor-α, and interleukin-6 levels, as well as lower levels of nuclear factor-erythroid 2-related factor-2 and glutathione peroxidase (P = 0.001, Bonferroni-corrected t test). In this model of diet-induced obesity, a 1-hour propofol infusion

  3. Pulsatile flow and oxygen transport past cylindrical fiber arrays for an artificial lung: computational and experimental studies.

    PubMed

    Zierenberg, Jennifer R; Fujioka, Hideki; Cook, Keith E; Grotberg, James B

    2008-06-01

    The influence of time-dependent flows on oxygen transport from hollow fibers was computationally and experimentally investigated. The fluid average pressure drop, a measure of resistance, and the work required by the heart to drive fluid past the hollow fibers were also computationally explored. This study has particular relevance to the development of an artificial lung, which is perfused by blood leaving the right ventricle and in some cases passing through a compliance chamber before entering the device. Computational studies modeled the fiber bundle using cylindrical fiber arrays arranged in in-line and staggered rectangular configurations. The flow leaving the compliance chamber was modeled as dampened pulsatile and consisted of a sinusoidal perturbation superimposed on a steady flow. The right ventricular flow was modeled to depict the period of rapid flow acceleration and then deceleration during systole followed by zero flow during diastole. Experimental studies examined oxygen transfer across a fiber bundle with either steady, dampened pulsatile, or right ventricular flow. It was observed that the dampened pulsatile flow yielded similar oxygen transport efficiency to the steady flow, while the right ventricular flow resulted in smaller oxygen transport efficiency, with the decrease increasing with Re. Both computations and experiments yielded qualitatively similar results. In the computational modeling, the average pressure drop was similar for steady and dampened pulsatile flows and larger for right ventricular flow while the pump work required of the heart was greatest for right ventricular flow followed by dampened pulsatile flow and then steady flow. In conclusion, dampening the artificial lung inlet flow would be expected to maximize oxygen transport, minimize work, and thus improve performance.

  4. Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia.

    PubMed

    de Magalhães, Raquel F; Samary, Cynthia S; Santos, Raquel S; de Oliveira, Milena V; Rocha, Nazareth N; Santos, Cintia L; Kitoko, Jamil; Silva, Carlos A M; Hildebrandt, Caroline L; Goncalves-de-Albuquerque, Cassiano F; Silva, Adriana R; Faria-Neto, Hugo C; Martins, Vanessa; Capelozzi, Vera L; Huhle, Robert; Morales, Marcelo M; Olsen, Priscilla; Pelosi, Paolo; de Abreu, Marcelo Gama; Rocco, Patricia R M; Silva, Pedro L

    2016-11-25

    Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (VT) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia. Thirty-two Wistar rats were randomly assigned to receive intratracheal of Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals were anesthetized and ventilated for 2 h with either conventional volume-controlled (VCV) or variable volume-controlled ventilation (VV), with mean VT = 6 mL/kg, PEEP = 5cmH2O, and FiO2 = 0.4. During VV, tidal volume varied randomly with a coefficient of variation of 30% and a Gaussian distribution. Additional animals assigned to receive either PA or SAL (n = 8/group) were not ventilated (NV) to serve as controls. In both SAL and PA, VV improved oxygenation and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6 expression compared to VCV (median [interquartile range]: 1.3 [0.3-2.3] vs. 5.3 [3.6-7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV (2.5 [1.9-3.5] vs. 1.2 [0.8-1.2]; p = 0.0005). In PA, compared to VCV, VV reduced perivascular edema (2.5 [2.0-3.75] vs. 6.0 [4.5-6.0]; p < 0.0001), septum neutrophils (2.0 [1.0-4.0] vs. 5.0 [3.3-6.0]; p = 0.0008), necrotizing vasculitis (3.0 [2.0-5.5] vs. 6.0 [6.0-6.0]; p = 0.0003), and ultrastructural lung damage scores (16 [14-17] vs. 24 [14-27], p < 0.0001). Blood colony-forming-unit (CFU) counts

  5. Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury.

    PubMed

    Reis, Fernando Fonseca Dos; Reboredo, Maycon de Moura; Lucinda, Leda Marília Fonseca; Bianchi, Aydra Mendes Almeida; Rabelo, Maria Aparecida Esteves; Fonseca, Lídia Maria Carneiro da; Oliveira, Júlio César Abreu de; Pinheiro, Bruno Valle

    2016-01-01

    To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. Wistar rats were allocated to one of three groups: pre-VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p < 0.05). Administration of dexamethasone prior to VILI induction decreased the severity of the lung injury. At 4 h and 24 h after induction, the ALI score in the dexamethasone group was not significantly different from that observed for the sham group and was lower than that observed for the control group (p < 0.05). Neutrophil counts in BAL fluid were increased in the control and dexamethasone groups, peaking at 4 h after VILI induction (p < 0.05). However, the neutrophil counts were lower in the dexamethasone group than in the control group at 4 h and 24 h after induction (p < 0.05). Pre-treatment with dexamethasone also prevented the post-induction oxygenation impairment seen in the control group. Administration of dexamethasone prior to VILI induction attenuates the effects of the injury in Wistar rats. The molecular mechanisms of such injury and the possible clinical role of corticosteroids in VILI have yet to be elucidated. Avaliar os efeitos da administração de dexametasona antes da indução de lesão pulmonar induzida por ventilação mecânica (LPIVM) na evolução temporal dessa lesão. Ratos Wistar foram alocados em um dos três grupos: administração de dexametasona pr

  6. Lung Functional and Biologic Responses to Variable Ventilation in Experimental Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome.

    PubMed

    Samary, Cynthia S; Moraes, Lillian; Santos, Cintia L; Huhle, Robert; Santos, Raquel S; Ornellas, Debora S; Felix, Nathane S; Capelozzi, Vera L; Schanaider, Alberto; Pelosi, Paolo; de Abreu, Marcelo Gama; Rocco, Patricia R M; Silva, Pedro L

    2016-07-01

    The biologic effects of variable ventilation may depend on the etiology of acute respiratory distress syndrome. We compared variable and conventional ventilation in experimental pulmonary and extrapulmonary acute respiratory distress syndrome. Prospective, randomized, controlled experimental study. University research laboratory. Twenty-four Wistar rats. Acute respiratory distress syndrome was induced by Escherichia coli lipopolysaccharide administered intratracheally (pulmonary acute respiratory distress syndrome, n = 12) or intraperitoneally (extrapulmonary acute respiratory distress syndrome, n = 12). After 24 hours, animals were randomly assigned to receive conventional (volume-controlled ventilation, n = 6) or variable ventilation (n = 6). Nonventilated animals (n = 4 per etiology) were used for comparison of diffuse alveolar damage, E-cadherin, and molecular biology variables. Variable ventilation was applied on a breath-to-breath basis as a sequence of randomly generated tidal volume values (n = 600; mean tidal volume = 6 mL/kg), with a 30% coefficient of variation (normal distribution). After randomization, animals were ventilated for 1 hour and lungs were removed for histology and molecular biology analysis. Variable ventilation improved oxygenation and reduced lung elastance compared with volume-controlled ventilation in both acute respiratory distress syndrome etiologies. In pulmonary acute respiratory distress syndrome, but not in extrapulmonary acute respiratory distress syndrome, variable ventilation 1) decreased total diffuse alveolar damage (median [interquartile range]: volume-controlled ventilation, 12 [11-17] vs variable ventilation, 9 [8-10]; p < 0.01), interleukin-6 expression (volume-controlled ventilation, 21.5 [18.3-23.3] vs variable ventilation, 5.6 [4.6-12.1]; p < 0.001), and angiopoietin-2/angiopoietin-1 ratio (volume-controlled ventilation, 2.0 [1.3-2.1] vs variable ventilation, 0.7 [0.6-1.4]; p < 0.05) and increased relative

  7. Detection of anatomical changes in lung cancer patients with 2D time-integrated, 2D time-resolved and 3D time-integrated portal dosimetry: a simulation study

    NASA Astrophysics Data System (ADS)

    Wolfs, Cecile J. A.; Brás, Mariana G.; Schyns, Lotte E. J. R.; Nijsten, Sebastiaan M. J. J. G.; van Elmpt, Wouter; Scheib, Stefan G.; Baltes, Christof; Podesta, Mark; Verhaegen, Frank

    2017-08-01

    The aim of this work is to assess the performance of 2D time-integrated (2D-TI), 2D time-resolved (2D-TR) and 3D time-integrated (3D-TI) portal dosimetry in detecting dose discrepancies between the planned and (simulated) delivered dose caused by simulated changes in the anatomy of lung cancer patients. For six lung cancer patients, tumor shift, tumor regression and pleural effusion are simulated by modifying their CT images. Based on the modified CT images, time-integrated (TI) and time-resolved (TR) portal dose images (PDIs) are simulated and 3D-TI doses are calculated. The modified and original PDIs and 3D doses are compared by a gamma analysis with various gamma criteria. Furthermore, the difference in the D 95% (ΔD 95%) of the GTV is calculated and used as a gold standard. The correlation between the gamma fail rate and the ΔD 95% is investigated, as well the sensitivity and specificity of all combinations of portal dosimetry method, gamma criteria and gamma fail rate threshold. On the individual patient level, there is a correlation between the gamma fail rate and the ΔD 95%, which cannot be found at the group level. The sensitivity and specificity analysis showed that there is not one combination of portal dosimetry method, gamma criteria and gamma fail rate threshold that can detect all simulated anatomical changes. This work shows that it will be more beneficial to relate portal dosimetry and DVH analysis on the patient level, rather than trying to quantify a relationship for a group of patients. With regards to optimizing sensitivity and specificity, different combinations of portal dosimetry method, gamma criteria and gamma fail rate should be used to optimally detect certain types of anatomical changes.

  8. Detection of anatomical changes in lung cancer patients with 2D time-integrated, 2D time-resolved and 3D time-integrated portal dosimetry: a simulation study.

    PubMed

    Wolfs, Cecile J A; Brás, Mariana G; Schyns, Lotte E J R; Nijsten, Sebastiaan M J J G; van Elmpt, Wouter; Scheib, Stefan G; Baltes, Christof; Podesta, Mark; Verhaegen, Frank

    2017-07-12

    The aim of this work is to assess the performance of 2D time-integrated (2D-TI), 2D time-resolved (2D-TR) and 3D time-integrated (3D-TI) portal dosimetry in detecting dose discrepancies between the planned and (simulated) delivered dose caused by simulated changes in the anatomy of lung cancer patients. For six lung cancer patients, tumor shift, tumor regression and pleural effusion are simulated by modifying their CT images. Based on the modified CT images, time-integrated (TI) and time-resolved (TR) portal dose images (PDIs) are simulated and 3D-TI doses are calculated. The modified and original PDIs and 3D doses are compared by a gamma analysis with various gamma criteria. Furthermore, the difference in the D 95% (ΔD 95%) of the GTV is calculated and used as a gold standard. The correlation between the gamma fail rate and the ΔD 95% is investigated, as well the sensitivity and specificity of all combinations of portal dosimetry method, gamma criteria and gamma fail rate threshold. On the individual patient level, there is a correlation between the gamma fail rate and the ΔD 95%, which cannot be found at the group level. The sensitivity and specificity analysis showed that there is not one combination of portal dosimetry method, gamma criteria and gamma fail rate threshold that can detect all simulated anatomical changes. This work shows that it will be more beneficial to relate portal dosimetry and DVH analysis on the patient level, rather than trying to quantify a relationship for a group of patients. With regards to optimizing sensitivity and specificity, different combinations of portal dosimetry method, gamma criteria and gamma fail rate should be used to optimally detect certain types of anatomical changes.

  9. Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma.

    PubMed

    de Castro, Ligia Lins; Xisto, Debora Gonçalves; Kitoko, Jamil Zola; Cruz, Fernanda Ferreira; Olsen, Priscilla Christina; Redondo, Patricia Albuquerque Garcia; Ferreira, Tatiana Paula Teixeira; Weiss, Daniel Jay; Martins, Marco Aurélio; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

    2017-06-24

    Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 10(5) human AD-MSCs, or EVs (released by 10(5) AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3(+)CD4(+) T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3(+)CD4(+) T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3(+)CD4(+) T cells in the mediastinal lymph nodes. In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different

  10. High pressure and time resolved studies of optical properties of n-type doped GaN/AlN multi-quantum wells: Experimental and theoretical analysis

    SciTech Connect

    Kaminska, A.; Jankowski, D.; Sobczak, K.; Beeler, M.; Monroy, E.; Borysiuk, J.

    2016-09-07

    High-pressure and time-resolved studies of the optical emission from n-type doped GaN/AlN multi-quantum-wells (MQWs) with various well thicknesses are analysed in comparison with ab initio calculations of the electronic (band structure, density of states) and optical (emission energies and their pressure derivatives, oscillator strength) properties. The optical properties of GaN/AlN MQWs are strongly affected by quantum confinement and polarization-induced electric fields. Thus, the photoluminescence (PL) peak energy decreases by over 1 eV with quantum well (QW) thicknesses increasing from 1 to 6 nm. Furthermore, the respective PL decay times increased from about 1 ns up to 10 μs, due to the strong built-in electric field. It was also shown that the band gap pressure coefficients are significantly reduced in MQWs as compared to bulk AlN and GaN crystals. Such coefficients are strongly dependent on the geometric factors such as the thickness of the wells and barriers. The transition energies, their oscillator strength, and pressure dependence are modeled for tetragonally strained structures of the same geometry using a full tensorial representation of the strain in the MQWs under external pressure. These MQWs were simulated directly using density functional theory calculations, taking into account two different systems: the semi-insulating QWs and the n-doped QWs with the same charge density as in the experimental samples. Such an approach allowed an assessment of the impact of n-type doping on optical properties of GaN/AlN MQWs. We find a good agreement between these two approaches and between theory and experimental results. We can therefore confirm that the nonlinear effects induced by the tetragonal strain related to the lattice mismatch between the substrates and the polar MQWs are responsible for the drastic decrease of the pressure coefficients observed experimentally.

  11. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo.

    PubMed

    Vendetti, Frank P; Lau, Alan; Schamus, Sandra; Conrads, Thomas P; O'Connor, Mark J; Bakkenist, Christopher J

    2015-12-29

    ATR and ATM are DNA damage signaling kinases that phosphorylate several thousand substrates. ATR kinase activity is increased at damaged replication forks and resected DNA double-strand breaks (DSBs). ATM kinase activity is increased at DSBs. ATM has been widely studied since ataxia telangiectasia individuals who express no ATM protein are the most radiosensitive patients identified. Since ATM is not an essential protein, it is widely believed that ATM kinase inhibitors will be well-tolerated in the clinic. ATR has been widely studied, but advances have been complicated by the finding that ATR is an essential protein and it is widely believed that ATR kinase inhibitors will be toxic in the clinic. We describe AZD6738, an orally active and bioavailable ATR kinase inhibitor. AZD6738 induces cell death and senescence in non-small cell lung cancer (NSCLC) cell lines. AZD6738 potentiates the cytotoxicity of cisplatin and gemcitabine in NSCLC cell lines with intact ATM kinase signaling, and potently synergizes with cisplatin in ATM-deficient NSCLC cells. In contrast to expectations, daily administration of AZD6738 and ATR kinase inhibition for 14 consecutive days is tolerated in mice and enhances the therapeutic efficacy of cisplatin in xenograft models. Remarkably, the combination of cisplatin and AZD6738 resolves ATM-deficient lung cancer xenografts.

  12. Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer.

    PubMed Central

    Macaulay, V. M.; Smith, I. E.; Everard, M. J.; Teale, J. D.; Reubi, J. C.; Millar, J. L.

    1991-01-01

    We have detected somatostatin receptors (SSR) by autoradiography in 3/4 established small cell lung cancer (SCLC) cell lines but not in two non-SCLC cell lines. The growth of 1/3 SSR positive SCLC cell lines was significantly inhibited by the long-acting somatostatin analogue octreotide (SMS 201-995, Sandostatin) 10(-9) M. We treated 20 SCLC patients with octreotide 250 micrograms three times daily for 1 week prechemotherapy (six patients) or at relapse after chemotherapy (14). Octreotide was well tolerated, and serum insulin-like growth factor-I levels were suppressed to 62 +/- 7% of pre-treatment levels. However there was no evidence of anti-tumour activity measured by tumour bulk or serum levels of neuron-specific enolase. In one patient metastatic skin nodules were shown to be SSR positive before and at the end of 2 weeks octreotide. Despite this the patient had progressive disease, and tumour cells obtained by fine needle aspirate before and after treatment showed no growth inhibition when cultured with octreotide immediately or following establishment as a cell line. In summary we saw little correlation between SSR expression and growth inhibition by octreotide, either in vitro or clinically. Images Figure 4 PMID:1654981

  13. Exogenous surfactant suppresses inflammation in experimental endotoxin-induced lung injury.

    PubMed

    Mittal, Neha; Sanyal, Sankar Nath

    2009-01-01

    Our objective was to evaluate the anti-inflammatory effects of exogenous surfactant and surfactant phospholipids on the lipopolysaccharide (LPS)-induced lung injury. Exogenous surfactant (porcine surfactant) and surfactant phospholipid (dipalmitoyl phospholipid DPPC, hexadecanol, tylaxopol) were instilled intratracheally with LPS in rats. Expression of surfactant apoproteins (SP-A) and the cyclooxygenase enzymes (COX-1 and -2) was studied by immunohistochemistry, and apoptosis was analyzed by in situ terminal dUTP nick end labeling TUNEL assay. The intracellular reactive oxygen species (ROS) was measured in the isolated macrophages by fluorescence measurement with dichlorofluorescein diacetate (DCFH-DA). LPS-induced oxidative burst and apoptosis at 72 hours were reduced by both porcine and synthetic surfactant. SP-A as well as COX-1 and -2 expressions were suppressed with synthetic surfactant treatment, whereas with porcine surfactant (P-SF) the SP-A expression was enhanced in response to LPS administration. These results indicate that exogenous surfactant inhibits LPS-induced inflammation. This anti-inflammatory activity may be an important outcome of surfactant therapy in endotoxin-induced respiratory distress.

  14. RESOLVE Project

    NASA Technical Reports Server (NTRS)

    Parker, Ray O.

    2012-01-01

    The RESOLVE project is a lunar prospecting mission whose primary goal is to characterize water and other volatiles in lunar regolith. The Lunar Advanced Volatiles Analysis (LAVA) subsystem is comprised of a fluid subsystem that transports flow to the gas chromatograph- mass spectrometer (GC-MS) instruments that characterize volatiles and the Water Droplet Demonstration (WDD) that will capture and display water condensation in the gas stream. The LAVA Engineering Test Unit (ETU) is undergoing risk reduction testing this summer and fall within a vacuum chamber to understand and characterize C!Jmponent and integrated system performance. Ray will be assisting with component testing of line heaters, printed circuit heaters, pressure transducers, temperature sensors, regulators, and valves in atmospheric and vacuum environments. He will be developing procedures to guide these tests and test reports to analyze and draw conclusions from the data. In addition, he will gain experience with preparing a vacuum chamber with fluid and electrical connections. Further testing will include integrated testing of the fluid subsystem with the gas supply system, near-infrared spectrometer, WDD, Sample Delivery System, and GC-MS in the vacuum chamber. This testing will provide hands-on exposure to a flight forward spaceflight subsystem, the processes associated with testing equipment in a vacuum chamber, and experience working in a laboratory setting. Examples of specific analysis Ray will conduct include: pneumatic analysis to calculate the WOO's efficiency at extracting water vapor from the gas stream to form condensation; thermal analysis of the conduction and radiation along a line connecting two thermal masses; and proportional-integral-derivative (PID) heater control analysis. In this Research and Technology environment, Ray will be asked to problem solve real-time as issues arise. Since LAVA is a scientific subsystem, Ray will be utilizing his chemical engineering background to

  15. Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis.

    PubMed

    Kalpana Deepa Priya, D; Gayathri, R; Gunassekaran, G R; Murugan, S; Sakthisekaran, D

    2013-05-01

    Sulforaphane (SFN) [1-isothiocyanato-4-(methylsulfinyl)butane] is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)]. Since it is among the most potent bioactive components with antioxidant and antitumor properties, it has received intense attention in the recent years for its chemopreventive properties. The present work determined the rehabilitating role in alleviating the oxidative damage caused by benzo(a)pyrene [B(a)P] to biomolecules and the apoptotic cascade mediated by orally administered isothiocyanate-SFN (9 µmol/mouse/day) against B(a)P (100 mg/kg body weight, i.p.) induced pulmonary carcinogenesis in Swiss albino mice. Oxidative damage was assessed by measuring lipid peroxidation, 8-hydroxydeoxyguanosine, hydrogen peroxide (H2O2) production, glycoprotein components, protein carbonyl levels and DNA-protein crosslinks. DNA fragmentation by agarose gel electrophoresis and caspase-3 activity by ELISA proved apoptotic induction by SFN along with the protein expression of Bcl-2, Bax and Cyt c. SFN treatment was found to decrease the H2O2 production (p < 0.001) in cancer induced animals, proving its antioxidant potential. Apoptosis was induced by increasing the release of Cyt c (p < 0.001) from mitochondria, decreasing and increasing the expression of Bcl-2 (p < 0.01) and Bax (p < 0.001), respectively. Caspase-3 activity was also enhanced (p < 0.001) which leads to DNA fragmentation in SFN treated groups. Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.

  16. Protective function of pirfenidone and everolimus on the development of chronic allograft rejection after experimental lung transplantation.

    PubMed

    von Suesskind-Schwendi, M; Heigel, E; Pfaehler, S; Haneya, A; Schmid, C; Hirt, S W; Lehle, K

    2016-07-01

    Long-term survival of lung allografts is limited by chronic rejection (CR). Oxidative stress (OxS) plays a central role in the development of CR. We investigated the influence of pirfenidone (alone or in combination with everolimus) on OxS and CR. A rat model of left lung allo-transplantation (F344-to-WKY) was used to evaluate the effects of pirfenidone alone [0,85% in chow from postoperative day (POD) -3 to 20/60] and in combination with everolimus [2,5 mg/kg bw daily from POD 7 to 20/60]. Allografts of non-treated animals, everolimus treated animals and right, non-transplanted lungs were used as references. Immunohistology of myeloperoxidase (MPO), haemoxygenase-1 (HO-1), iron and platelet-derived-growth-factor-receptor-alpha (PDGFR-a) were performed. On POD 20, all groups showed severe acute rejection (ISHLT A3-4/B1R-B2R). Groups treated with pirfenidone showed a lower interstitial inflammatory infiltration and a lower participation of highly fibrotic degenerated vessels (ISHLT-D2R). In the long term follow up (POD 60), pirfenidone alone significantly reduced chronic airway rejection (ISHLT-C; p≤0.05), interstitial fibrosis (IF; p≤0.05), content of collagen (p≤0.05), expression of PDGFR-a (p≤0.05) and the deposition of iron (p≤0.05). All groups treated with pirfenidone showed a high expression of the cytoprotective enzyme HO-1 (p≤0.05). The additional application of everolimus resulted in a significant decrease of chronic airway rejection (ISHLT-C; p≤0.05), vasculopathy (ISHLT; p≤0.05) and IF (p≤0.05). In conclusion, early application of pirfenidone inhibited the progression of CR by its anti-fibrotic and anti-oxidative properties. The additional application of an m-TOR-inhibitor increased the anti-fibrotic effects of pirfenidone which resulted in a reduction of CR after experimental LTx.

  17. Cardiorespiratory effects of spontaneous breathing in two different models of experimental lung injury: a randomized controlled trial

    PubMed Central

    Varelmann, Dirk; Muders, Thomas; Zinserling, Jörg; Guenther, Ulf; Magnusson, Anders; Hedenstierna, Göran; Putensen, Christian; Wrigge, Hermann

    2008-01-01

    Introduction Acute lung injury (ALI) can result from various insults to the pulmonary tissue. Experimental and clinical data suggest that spontaneous breathing (SB) during pressure-controlled ventilation (PCV) in ALI results in better lung aeration and improved oxygenation. Our objective was to evaluate whether the addition of SB has different effects in two different models of ALI. Methods Forty-four pigs were randomly assigned to ALI resulting either from hydrochloric acid aspiration (HCl-ALI) or from increased intra-abdominal pressure plus intravenous oleic acid injections (OA-ALI) and were ventilated in PCV mode either with SB (PCV + SB) or without SB (PCV – SB). Cardiorespiratory variables were measured at baseline after induction of ALI and after 4 hours of treatment (PCV + SB or PCV – SB). Finally, density distributions and end-expiratory lung volume (EELV) were assessed by thoracic spiral computed tomography. Results PCV + SB improved arterial partial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2) by a reduction in intrapulmonary shunt fraction in HCl-ALI from 27% ± 6% to 23% ± 13% and in OA-ALI from 33% ± 19% to 26% ± 18%, whereas during PCV – SB PaO2/FiO2 deteriorated and shunt fraction increased in the HCl group from 28% ± 8% to 37% ± 17% and in the OA group from 32% ± 12% to 47% ± 17% (P < 0.05 for interaction time and treatment, but not ALI type). PCV + SB also resulted in higher EELV (HCl-ALI: 606 ± 171 mL, OA-ALI: 439 ± 90 mL) as compared with PCV – SB (HCl-ALI: 372 ± 130 mL, OA-ALI: 192 ± 51 mL, with P < 0.05 for interaction of time, treatment, and ALI type). Conclusions SB improves oxygenation, reduces shunt fraction, and increases EELV in both models of ALI. PMID:18980696

  18. Selective recruitment maneuvers for lobar atelectasis: effects on lung function and central hemodynamics: an experimental study in pigs.

    PubMed

    Hansen, Lars Kjaersgaard; Sloth, Erik; Nielsen, Jonas; Koefoed-Nielsen, Jacob; Lambert, Per; Lunde, Søren; Larsson, Anders

    2006-05-01

    We investigated whether selective lung recruitment of a lobar collapse would improve oxygenation and lung volume as well as a general (global) lung recruitment maneuver, with fewer circulatory side effects. In 10 ventilated, anesthetized pigs, a bronchial blocker was inserted in the right lower lobe, which was selectively lavaged to create a dense lobar collapse. The pigs were randomized into two orders of lung recruitment maneuvers (40 cm H2O airway pressure for 30 s): either a selective lung recruitment maneuver (using the inner lumen of the bronchial blocker) followed by a general lung recruitment maneuver, or vice versa. Median end-expiratory lung volume and median Pao2 increased significantly by approximately 100 mL and 16 kPa, respectively, with no significant differences between the two recruitment methods. There were no circulatory changes during the selective lung recruitment maneuver, but during the general lung recruitment maneuver, mean arterial blood pressure decreased significantly by 36 (21, 41) mm Hg (median, 25th and 75th percentiles), cardiac output by 2.1 (1.6, 2.5) L/min and left ventricular end-diastolic area by 4.4 (3.5, 4.5) cm2. In conclusion, a selective recruitment maneuver improved lung function similar to a general lung recruitment maneuver but without any circulatory side effects.

  19. In Vitro Experimental Model for the Long-Term Analysis of Cellular Dynamics During Bronchial Tree Development from Lung Epithelial Cells.

    PubMed

    Hagiwara, Masaya; Maruta, Naomichi; Marumoto, Moegi

    2017-06-01

    Lung branching morphogenesis has been studied for decades, but the underlying developmental mechanisms are still not fully understood. Cellular movements dynamically change during the branching process, but it is difficult to observe long-term cellular dynamics by in vivo or tissue culture experiments. Therefore, developing an in vitro experimental model of bronchial tree would provide an essential tool for developmental biology, pathology, and systems biology. In this study, we succeeded in reconstructing a bronchial tree in vitro by using primary human bronchial epithelial cells. A high concentration gradient of bronchial epithelial cells was required for branching initiation, whereas homogeneously distributed endothelial cells induced the formation of successive branches. Subsequently, the branches grew in size to the order of millimeter. The developed model contains only two types of cells and it facilitates the analysis of lung branching morphogenesis. By taking advantage of our experimental model, we carried out long-term time-lapse observations, which revealed self-assembly, collective migration with leader cells, rotational motion, and spiral motion of epithelial cells in each developmental event. Mathematical simulation was also carried out to analyze the self-assembly process and it revealed simple rules that govern cellular dynamics. Our experimental model has provided many new insights into lung development and it has the potential to accelerate the study of developmental mechanisms, pattern formation, left-right asymmetry, and disease pathogenesis of the human lung.

  20. Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

    PubMed

    Thompson, Sophie M; Connell, Marilyn G; van Kuppevelt, Toin H; Xu, Ruoyan; Turnbull, Jeremy E; Losty, Paul D; Fernig, David G; Jesudason, Edwin C

    2011-06-14

    Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme.We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional

  1. Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

    PubMed Central

    2011-01-01

    Background Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. Results The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme. We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. Conclusions The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by

  2. Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

    PubMed

    Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-09-01

    To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005). In this experimental model, Acute Respiratory Distress Syndrome Network and open lung approach affected pulmonary vascular mechanics similarly

  3. Experimental investigation into the impact of a liquid droplet onto a granular bed using three-dimensional, time-resolved, particle tracking.

    PubMed

    Long, Edward J; Hargrave, Graham K; Cooper, James R; Kitchener, Ben G B; Parsons, Anthony J; Hewett, Caspar J M; Wainwright, John

    2014-03-01

    An experimental investigation into the interaction that occurs between an impacting water droplet and a granular bed of loose graded sand has been carried out. High-speed imaging, three-dimensional time-resolved particle tracking, and photogrammetric surface profiling have been used to examine individual impact events. The focus of the study is the quantification and trajectory analysis of the particles ejected from the sand bed, along with measurement of the change in bed morphology. The results from the experiments have detailed two distinct mechanisms of particle ejection: the ejection of water-encapsulated particles from the edge of the wetted region and the ejection of dry sand from the periphery of the impact crater. That the process occurs by these two distinct mechanisms has hitherto been unobserved. Presented in the paper are distributions of the particle ejection velocities, angles, and transport distances for both mechanisms. The ejected water-encapsulated particles, which are few in number, are characterized by low ejection angles and high ejection velocities, leading to large transport distances; the ejected dry particles, which are much greater in number, are characterized by high ejection angles and low velocities, leading to lower transport distances. From the particle ejection data, the momentum of the individual ballistic sand particles has been calculated; it was found that only 2% of the water-droplet momentum at impact is transferred to the ballistic sand particles. In addition to the particle tracking, surface profiling of the granular bed postimpact has provided detailed information on its morphology; these data have demonstrated the consistent nature of the craters produced by the impact and suggest that particle agglomerations released from their edges make up about twice the number of particles involved in ballistic ejection. It is estimated that, overall, about 4% of the water-droplet momentum is taken up in particle movement.

  4. Ventilation with biphasic positive airway pressure in experimental lung injury. Influence of transpulmonary pressure on gas exchange and haemodynamics.

    PubMed

    Henzler, Dietrich; Dembinski, Rolf; Bensberg, Ralf; Hochhausen, Nadine; Rossaint, Rolf; Kuhlen, Ralf

    2004-05-01

    We investigated whether improvement in ventilation perfusion (.V(A)/.Q) distribution during mechanical ventilation using biphasic positive airway pressure (BIPAP) with spontaneous breathing may be attributed to an effectively increased transpulmonary pressure (P(TP)) and can also be achieved by increasing P(TP) during controlled ventilation. In 12 pigs with saline lavage-induced lung injury we compared the effects of BIPAP to pressure-controlled ventilation with equal airway pressure (PCV(AW)) or equal transpulmonary pressure (PCV(TP)) on V(A)/.Q distribution assessed by the multiple inert gas elimination technique (MIGET). Animal laboratory study. Intrapulmonary shunt was 33+/-11% during BIPAP, 36+/-10% during PCV(AW) and 33+/-15% during PCV(TP) ( p= n.s.). BIPAP resulted in higher PaO(2) than PCV(AW) (188+/-83 versus 147+/-82 mmHg, p < 0.05), but not than PCV(TP) (187+/-139 mmHg). Oxygen delivery was significantly higher during BIPAP (530+/-109 ml/min) versus 374+/-113 ml/min during PCV(AW) and 353+/-93 ml/min during PCV(TP) ( p < 0.005). Tidal volume with PCV(TP) increased to 11.9+/-2.3 ml/kg, compared to 8.5+/-0.8 with BIPAP and 7.6+/-1.4 with PCV(AW) ( p <0.001) and cardiac output decreased to 3.5+/-0.6 l/min (BIPAP 4.9+/-0.8 and PCV(AW) 3.9+/-0.8, p<0.006). In experimental lung injury, BIPAP with preserved spontaneous breathing was effective in increasing regional P(TP), since pressure-controlled ventilation with the same P(TP) resulted in similar gas exchange effects. However, PCV(TP) caused increased airway pressures and tidal volumes, whereby, with BIPAP, less depression of oxygen delivery and cardiac output were observed. BIPAP could be useful in maintaining pulmonary gas exchange and slightly improving oxygenation without interfering with circulation as strongly as PCV does.

  5. Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice.

    PubMed

    Viby, Niels-Erik; Isidor, Marie S; Buggeskov, Katrine B; Poulsen, Steen S; Hansen, Jacob B; Kissow, Hannelouise

    2013-12-01

    The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP-1 displays antiinflammatory and surfactant-releasing effects. Thus, we hypothesize that treatment with GLP-1 analogs will improve pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with a measurement of enhanced pause in a whole-body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Enhanced pause increased dramatically at day 17 in all control mice, but the increase was significantly less in the groups of GLP-1R agonist-treated mice (P < .001). Survival proportions were significantly increased in GLP-1R agonist-treated mice (P < .01). SFTPB and SFTPA were down-regulated and the expression of inflammatory cytokines were increased in mice with obstructive lung disease, but levels were largely unaffected by GLP-1R agonist treatment. These results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive pulmonary disease, by decreasing the severity of acute exacerbations. The mechanism of action does not seem to be the modulation of inflammation and SFTP expression.

  6. Altered Lipid Composition of Surfactant and Lung Tissue in Murine Experimental Malaria-Associated Acute Respiratory Distress Syndrome

    PubMed Central

    Scaccabarozzi, Diletta; Deroost, Katrien; Lays, Natacha; Taramelli, Donatella

    2015-01-01

    Malaria-associated acute lung injury (MA-ALI) and its more severe form malaria-associated acute respiratory distress syndrome (MA-ARDS) are common, often fatal complications of severe malaria infections. However, little is known about their pathogenesis. In this study, biochemical alterations of the lipid composition of the lungs were investigated as possible contributing factors to the severity of murine MA-ALI/ARDS. C57BL/6J mice were infected with Plasmodium berghei NK65 to induce lethal MA-ARDS, or with Plasmodium chabaudi AS, a parasite strain that does not induce lung pathology. The lipid profile of the lung tissue from mice infected with Plasmodium berghei NK65 developing MA-ALI/ARDS, but not that from mice without lung pathology or controls, was characterized by high levels of phospholipids -mainly phosphatidylcholine- and esterified cholesterol. The high levels of polyunsaturated fatty acids and the linoleic/oleic fatty acid ratio of the latter reflect the fatty acid composition of plasma cholesterol esters. In spite of the increased total polyunsaturated fatty acid pool, which augments the relative oxidability of the lung membranes, and the presence of hemozoin, a known pro-oxidant, no excess oxidative stress was detected in the lungs of Plasmodium berghei NK65 infected mice. The bronchoalveolar lavage (BAL) fluid of Plasmodium berghei NK65 infected mice was characterized by high levels of plasma proteins. The phospholipid profile of BAL large and small aggregate fractions was also different from uninfected controls, with a significant increase in the amounts of sphingomyelin and lysophosphatidylcholine and the decrease in phosphatidylglycerol. Both the increase of proteins and lysophosphatidylcholine are known to decrease the intrinsic surface activity of surfactant. Together, these data indicate that an altered lipid composition of lung tissue and BAL fluid, partially ascribed to oedema and lipoprotein infiltration, is a characteristic feature of murine

  7. Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

    PubMed

    Bayat, Sam; Porra, Liisa; Broche, Ludovic; Albu, Gergely; Malaspinas, Iliona; Doras, Camille; Strengell, Satu; Peták, Ferenc; Habre, Walid

    2015-08-01

    We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (sV̇) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on sV̇ distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased sV̇ (P < 0.001) and sV̇ heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants.

  8. [An experimental study on the Chinese lung adenocarcinoma cell clone CPA-Yang1-BR with brain metastasis potency in nude mice and in vivo imaging research].

    PubMed

    Lei, Bei; Cao, Jie; Shen, Jie; Zhao, Lanxiang; Liang, Sheng; Meng, Qinggang; Xie, Wenhui; Yang, Shunfang

    2013-08-20

    Lung cancer is the leading cause of cancer-related death in men and women. It is also the most common cause of brain metastases. A brain metastasis model is difficult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. Thus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great significance. CPA-Yang1 cells were obtained from a patient with human lung adenocarcinoma by lentiviral vector-mediated transfection of green fluorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro ¹⁸F FDG-PET/CT scanners, small animal in vivo imaging system for fluorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. The samples were divided into two parts for cell culture and histological diagnosis. The process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. The use of MRI for the detection of brain metastases has obvious advantages. An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeficient mice. The results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

  9. Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema

    PubMed Central

    2013-01-01

    Background Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD). Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. Methods We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20) and 40 mg/mL (E40) papain. Results The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p < 0.05) and E40 (52.27 ± 4.7; crossed the alveolar intercepts) groups. As compared to the control group, there was a reduction on body (171.6 ± 15.9 g) and muscle weight (251.87 ± 24.87 mg) in the E20 group (157.5 ± 10.3 mg and 230.12 ± 23.52 mg, for body and muscle weight, respectively), which was accentuated in the E40 group (137.4 ± 7.2 g and 197.87 ± 10.49 mg, for body and muscle weight, respectively). Additionally, the thiobarbituric acid reactive substances (TBARS), tert-butyl hydroperoxide-initiated chemiluminescence (CL), carbonylated proteins, and chymotrypsin-like proteolytic activity were elevated in the E40 group as compared to the E20 group (p < 0.05 for all comparisons). The severity of emphysema significantly correlated with the progressive increase in CL (r = −0.95), TBARS (r = −0.98), carbonyl proteins (r = −0.99), and chymotrypsin-like proteolytic activity (r = −0.90). Furthermore, augmentation of proteolytic activity correlated significantly with CL (r = 0.97), TBARS (r = 0.96), and carbonyl proteins (r = 0.91). Conclusions Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin

  10. Theoretical and experimental study on the difference of the time-resolved fluorescence spectrum between the tumor and the adjacent normal tissue

    NASA Astrophysics Data System (ADS)

    Li, Mingzhao; Xu, Tao

    2006-09-01

    The objective of this paper is to study the difference of the time-resolved fluorescence spectrum between the tumor and the adjacent normal tissue. The time-resolved spectrum of the s-180 sarcoma tumor and adjacent normal tissue mediated by the Palladium-porphyrin photosensilizer (Pd-TCPP) is detected by a homemade instrumentation. An improved Monte Carlo algorithm, taking into account the depth of the upper layer tissue (z I) and the delay of the fluorescence photon emission for the time (τ) Pd-TCPP electrons spend in the excited state, is developed to study the reason of the spectrum difference formation. It is found from the experiment that the decay constant T decay of the time-resolved fluorescence spectrum of the tumor is obviously larger than that of the adjacent normal tissue. And T decay increased with the tumor growth, from 554μs in the first day to 634μs in the eighth day while it keeps steady for normal tissue. The simulated spectrum at different z I and different τ reveal that both the increase of z I and τ can delay the spectrum decay. It is believed that T decay of the tumor tissue should be larger than that of adjacent normal tissue because of the hypoxia. The changes of tumor size and oxygen status cause the difference of the time-resolved fluorescence spectrum between the tumor and the adjacent normal tissue and this fact can be made use of in the tumor diagnoses.

  11. Electrical impedance tomography compared to positron emission tomography for the measurement of regional lung ventilation: an experimental study

    PubMed Central

    Richard, JC; Pouzot, C; Gros, A; Tourevieille, C; Lebars, D; Lavenne, F; Frerichs, I; Guérin, C

    2009-01-01

    Introduction Electrical impedance tomography (EIT), which can assess regional lung ventilation at the bedside, has never been compared with positron-emission tomography (PET), a gold-standard to quantify regional ventilation. This experiment systematically compared both techniques in injured and non-injured lungs. Methods The study was performed in six mechanically ventilated female piglets. In normal lungs, tidal volume (VT) was randomly changed to 6, 8, 10 and 15 ml/kg on zero end-expiratory pressure (ZEEP), then, at VT 10 ml/kg, positive end-expiratory pressure (PEEP) was randomly changed to 5, 10 and 15 cmH2O. Afterwards, acute lung injury (ALI) was subsequently created in three animals by injecting 3 ml/kg hydrochloric acid into the trachea. Then at PEEP 5 cmH2O, VT was randomly changed to 8 and 12 ml/kg and PEEP of 10 and 15 cmH2O applied at VT 10 ml/kg. EIT and PET examinations were performed simultaneously. EIT ventilation (VTEIT) and lung volume (VL) were measured in the anterior and posterior area of each lung. On the same regions of interest, ventilation (VPET) and aerated lung volume (VAatten) were determined with PET. Results On ZEEP, VTEIT and VPET significantly correlated for global (VTEIT = VPET - 2E-13, R2 = 0.95, P < 0.001) and regional (VTEIT = 0.81VPET+7.65, R2 = 0.63, P < 0.001) ventilation over both conditions. For ALI condition, corresponding R2 were 0.91 and 0.73 (P < 0.01). Bias was = 0 and limits of agreement were -37.42 and +37.42 ml/min for global ventilation over both conditions. These values were 0.04 and -29.01 and +29.08 ml/min, respectively, for regional ventilation. Significant correlations were also found between VL and VAatten for global (VL = VAatten+1E-12, R2 = 0.93, P < 0.0001) and regional (VL = 0.99VAatten+0.92, R2 = 0.65, P < 0.001) volume. For ALI condition, corresponding R2 were 0.94 (P < 0.001) and 0.54 (P < 0.05). Bias was = 0 and limits of agreement ranged -38.16 and +38.16 ml for global ventilation over both

  12. Antioxidant and antitumor efficacy of Luteolin, a dietary flavone on benzo(a)pyrene-induced experimental lung carcinogenesis.

    PubMed

    Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Barua, Chandana C; Gogoi, Ranadeep

    2016-08-01

    The present study is designed to assess the antioxidant and antitumor potential of luteolin against benzo(a)pyrene [B(a)P]-induced lung carcinogenesis in Swiss albino mice. Here, we reported that oral administration of B(a)P (50mg/kg body weight) to mice resulted in raised lipid peroxides (LPO), lung specific tumor markers such as carcinoembryonic antigen (CEA) and neuron specific enolase (NSE) with concomitant decrease in the levels of both enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-s-transferase (GST), and non-enzymatic antioxidants such as reduced glutathione (GSH), vitamin E and vitamin C. Luteolin treatment (15mg/kg body weight, p.o) significantly counteracted all these alterations and maintained cellular normalcy. Moreover, assessment of protein expression levels by western blot analysis revealed that luteolin treatment effectively negates B(a)P-induced upregulated expression of proliferating cell nuclear antigen (PCNA), cytochrome P450 1A1 (CYP1A1) and nuclear factor-kappa B (NF-κB). Furthermore, histopathology of lung tissue and immunohistochemistry of CYP1A1 were carried out to substantiate the anti- lung cancer effect of luteolin. Overall, these findings confirm the chemopreventive potential of luteolin against B(a)P induced lung carcinogenesis.

  13. The backflow from the pulmonary circulation for identification of the aortic origin of the bronchial arteries in experimental left single lung transplantation.

    PubMed

    Berti, A; Nazari, S; Rescigno, G

    1995-01-01

    The ideal solution to the bronchial healing problems in lung transplant would be the reconstruction of the bronchial arteries at time of transplantation. The problems with this approach are essentially technical being difficult to identify and preserve the bronchial arteries in humans. The purpose of this paper is to report our experience with an experimental model in dog to easily identify and preserve bronchial circulation in single lung transplantation. The technique is based on the preservation during harvesting of the aortic origin of the first five couples of arterial orifices. Identification of the orifice(s) connected with the bronchial circulation is carried out by the backflow which takes place from the pulmonary circulation after organ reperfusion is resumed. The identified orifice(s) is then anastomosed to the descending recipient aorta, tangentially clamped.

  14. Lung [(18)F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation.

    PubMed

    Musch, Guido; Winkler, Tilo; Harris, R Scott; Vidal Melo, Marcos F; Wellman, Tyler J; de Prost, Nicolas; Kradin, Richard L; Venegas, Jose G

    2014-03-01

    Acute lung injury occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48-72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced acute lung injury. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, the authors hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of acute lung injury are not yet expected. In five sheep, the authors induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. The authors used positron emission tomography with: (1) [F]fluorodeoxyglucose to measure metabolic activity of pulmonary inflammatory cells; and (2) [N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. The pulmonary [F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min; P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage, there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02; P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01; P < 0 .05). Using noninvasive imaging, the authors demonstrated that increased pulmonary [F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation.

  15. THE DETERMINATION OF CORRELATION LINKAGES BETWEEN LEVEL OF REACTIVE OXYGEN SPECIES, CONTENTS OF NEUTROPHILES AND BLOOD GAS COMPOSITION IN EXPERIMENTAL ACUTE LUNG INJURY.

    PubMed

    Marushchak, M; Krynytska, I; Petrenko, N; Klishch, I

    2016-04-01

    Acute lung injury (ALI) remains a major cause of acute respiratory failure and death of patients. Despite the achievements at the current stage in treatment, morbidity and mortality of ALI remain high. However, a deeper understanding of the pathogenetic links of ALI, identifying of the predictors that positively or negatively influence on the course of the syndrome, the correlation between some pathogenetic mechanisms will improve therapeutic strategies for patients with ALI, which makes the actuality of this study. The aim of the research was to detect additional pathogenetic mechanisms of the acute lung injury development in rats based on a comparative analysis of the correlations between the level of reactive oxygen species in blood and bronchoalveolar lavage, contents of neutrophils and blood gas composition. The experiments were performed on 54 white nonlinear mature male rats 200-220g in weight. The animals were divided into 5 groups: the 1st - control group (n=6), the 2nd - animals affected by hydrochloric acid for 2 hours (n=12), the 3rd - animals affected by hydrochloric acid for 6 hours (n=12), the 4th - animals affected by hydrochloric acid for 12 hours (n=12), the 5th - animals affected by hydrochloric acid for 24 hours (n=12). Correlation analysis was performed between all the studied indices. Coefficient of linear correlation (r) and its fidelity (p) was calculated that was accordingly denoted in the tables (correlation matrices). The correlation coefficient was significant at p<0.05. Conducted correlative analysis showed that the level of ROS in neutrophils of blood in rats with modeled ALI had a high negative correlative linkage with pH of arterial blood in 2nd and 3rd experimental groups. Conducted correlative analysis of data in BAL showed that the level of ROS in neutrophils in rats with modeled ALI had a strong positive correlative relationship with the number of white blood cells in 3-rd, 4-th and 5-th experimental groups and positive

  16. Nicotine, acetylcholine and bombesin are trophic growth factors in neuroendocrine cell lines derived from experimental hamster lung tumors

    SciTech Connect

    Schueller, H.M.; Nylen, E.; Park, P.; Becker, K.L. George Washington Univ., Washington, DC )

    1990-01-01

    Neuroendocrine hamster lung tumors, induced by exposure to 60% hyperoxia and subcutaneous administration of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for 12 weeks, were placed in cell culture. By subsequent selective transfer of epithelial cells and maintenance in an atmosphere of 8% CO{sub 2}, cell lines with characteristics of neuroendocrine cells were established. The neuroendocrine markers expressed by these cell lines included electron dense neuroendocrine secretion granules as well as secretion of calcitonin and mammalian bombesin. In keeping with data previously reported for a human neuroendocrine lung tumor cell line, nicotine, acetylcholien, and mammalian bombesin (MB) acted as strongrowth factors in these neuroendocrine hamster tumor lines. The mitogenic effect of nicotine an acetylcholine was abolished by nicotinic receptor inhibition while the effects of mammalian bombesin were inhibited by an antagonist of MB receptors. Our data suggest that a receptor-mediated mitogenic effect of nicotine on neuroendocrine lung cells may be instrumental in the induction of smoking-associated small cell lung cancer.

  17. CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma and is an additional predictor for poor patient outcome.

    PubMed

    Gvozdenovic, Ana; Arlt, Matthias J E; Campanile, Carmen; Brennecke, Patrick; Husmann, Knut; Li, Yufei; Born, Walter; Muff, Roman; Fuchs, Bruno

    2013-04-01

    Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan-CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA-binding defective mutant R41A in osteoblastic SaOS-2 cells resulted in HA-independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS-2 cells resulted in an HA-dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44-associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. Copyright © 2013 American Society for Bone and Mineral Research.

  18. Humidification of base flow gas during adult high-frequency oscillatory ventilation: an experimental study using a lung model.

    PubMed

    Shiba, Naoki; Nagano, Osamu; Hirayama, Takahiro; Ichiba, Shingo; Ujike, Yoshihito

    2012-01-01

    In adult high-frequency oscillatory ventilation (HFOV) with an R100 artificial ventilator, exhaled gas from patient's lung may warm the temperature probe and thereby disturb the humidification of base flow (BF) gas. We measured the humidity of BF gas during HFOV with frequencies of 6, 8 and 10 Hz, maximum stroke volumes (SV) of 285, 205, and 160 ml at the respective frequencies, and, BFs of 20, 30, 40 l/min using an original lung model. The R100 device was equipped with a heated humidifier, Hummax Ⅱ, consisting of a porous hollow fiber in circuit. A 50-cm length of circuit was added between temperature probe (located at 50 cm proximal from Y-piece) and the hollow fiber. The lung model was made of a plastic container and a circuit equipped with another Hummax Ⅱ. The lung model temperature was controlled at 37℃. The Hummax Ⅱ of the R100 was inactivated in study-1 and was set at 35℃ or 37℃ in study-2. The humidity was measured at the distal end of the added circuit in study-1 and at the proximal end in study-2. In study-1, humidity was detected at 6 Hz (SV 285 ml) and BF 20 l/min, indicating the direct reach of the exhaled gas from the lung model to the temperature probe. In study-2 the absolute humidity of the BF gas decreased by increasing SV and by increasing BF and it was low with setting of 35℃. In this study setting, increasing the SV induced significant reduction of humidification of the BF gas during HFOV with R100.

  19. Furrier's lung

    PubMed Central

    Pimentel, J. Cortez

    1970-01-01

    As is known, the inhalation of animal hairs can provoke immunological reactions in the respiratory tract affecting the naso-tracheo-bronchial sector and giving rise to asthma-like syndromes. Another form of disease, found in furriers with long exposure to `hair dust', is described. It is characterized by a granulomatous interstitial pneumonia, of the tuberculoid type, very similar to that described in other diseases related to the inhalation of organic dusts, both vegetable and animal, such as `farmer's lung' and `bird fancier's lung'. This new disease—which we experimentally reproduced—can be diagnosed from the occupational history together with the finding on lung biopsy of hair shafts within granulomatous lesions (birefringence and histo-chemical reactions). As in other diseases of this type, a host factor of probable immunological nature is suggested. Attention is drawn to the need to protect workers in the furrier's trade. Images PMID:5484998

  20. Effects of ultraprotective ventilation, extracorporeal carbon dioxide removal, and spontaneous breathing on lung morphofunction and inflammation in experimental severe acute respiratory distress syndrome.

    PubMed

    Güldner, Andreas; Kiss, Thomas; Bluth, Thomas; Uhlig, Christopher; Braune, Anja; Carvalho, Nadja; Quast, Theresa; Rentzsch, Ines; Huhle, Robert; Spieth, Peter; Richter, Torsten; Saddy, Felipe; Rocco, Patricia R M; Kasper, Michael; Koch, Thea; Pelosi, Paolo; de Abreu, Marcelo Gama

    2015-03-01

    To investigate the role of ultraprotective mechanical ventilation (UP-MV) and extracorporeal carbon dioxide removal with and without spontaneous breathing (SB) to improve respiratory function and lung protection in experimental severe acute respiratory distress syndrome. Severe acute respiratory distress syndrome was induced by saline lung lavage and mechanical ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to 52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway pressure release ventilation) with: (1) conventional P-MV with VT ≈6 ml/kg (P-MVcontr); (2) UP-MV with VT ≈3 ml/kg (UP-MVcontr); (3) UP-MV with VT ≈3 ml/kg and SB (UP-MVspont); and (4) UP-MV with VT ≈3 ml/kg and pressure supported SB (UP-MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to 40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr; (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3) compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels of tumor necrosis factor-α (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0 to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5 to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7] pg/mg, respectively) in dorsal lung zones. In this model of severe acute respiratory distress syndrome, MV with VT ≈3 ml/kg and extracorporeal carbon dioxide removal without SB slightly reduced lung histologic damage, but not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV, pressure supported SB increased lung inflammation.

  1. Comparative analysis of the protective effects of caffeic acid phenethyl ester (CAPE) on pulmonary contusion lung oxidative stress and serum copper and zinc levels in experimental rat model.

    PubMed

    Sırmalı, Mehmet; Solak, Okan; Tezel, Cagatay; Sırmalı, Rana; Ginis, Zeynep; Atik, Dilek; Agackıran, Yetkin; Koylu, Halis; Delibas, Namık

    2013-01-01

    The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE) in the lungs by biochemical and histopathological analyses in an experimental isolated lung contusion model. Eighty-one male Sprague-Dawley rats were used. The animals were divided randomly into four groups: group 1 (n = 9) was defined as without contusion and without CAPE injection. Group 2 (n = 9) was defined as CAPE 10 μmol/kg injection without lung contusion. Group 3 (n = 36) was defined as contusion without CAPE-administrated group which consisted of four subgroups that were created according to analysis between days 0, 1, 2, and 3. Group 4 (n = 27) was defined as CAPE 10 μmol/kg administrated after contusion group divided into three subgroups according to analysis on days 1, 2, and 3. CAPE 10 μmol/kg was injected intraperitoneally 30 min after trauma and on days 1 and 2. Blood samples were obtained to measure catalase (CAT) and superoxide dismutase (SOD) activities and level of malondialdehyde (MDA) and for blood gas analysis. Trace elements such as zinc and copper were measured in serum. The lung tissue was also removed for histopathological examination. Isolated lung contusion increased serum and tissue SOD and CAT activities and MDA levels (p < 0.05). Both serum and tissue SOD, MDA, and CAT levels on day 3 were lower in group 4 compared to group 3 (p < 0.05). Further, the levels of SOD, MDA, and CAT in group 4 were similar compared to group 1 (p > 0.05). CAPE also had a significant beneficial effect on blood gases (p < 0.05). Both serum zinc and copper levels were (p < 0.05) influenced by the administration of CAPE. Histopathological examination revealed lower scores in group 4 compared to group 3 (p < 0.05) and no significant differences compared to group 1 (p > 0.05). CAPE appears to be effective in protecting against severe oxidative stress and tissue damage caused by pulmonary contusion in an

  2. Lung [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation

    PubMed Central

    Musch, Guido; Winkler, Tilo; Harris, R. Scott; Vidal Melo, Marcos F.; Wellman, Tyler J.; de Prost, Nicolas; Kradin, Richard L.; Venegas, Jose G.

    2014-01-01

    Background Acute lung injury (ALI) occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48 to 72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced ALI. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, we hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of ALI are not yet expected. Methods In five sheep we induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. We used positron emission tomography with: 1) [18F]fluorodeoxyglucose to measure pulmonary inflammatory cell metabolic activity; and 2) [13N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. Results The pulmonary [18F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min−1, P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02, P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01, P < 0.05). Conclusion Using noninvasive imaging we demonstrated that increased pulmonary [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation. PMID:24051392

  3. Diffusion of hyperpolarized 129Xe in the lung: a simplified model of 129Xe septal uptake and experimental results

    NASA Astrophysics Data System (ADS)

    Patz, Samuel; Muradyan, Iga; Hrovat, Mirko I.; Dabaghyan, Mikayel; Washko, George R.; Hatabu, Hiroto; Butler, James P.

    2011-01-01

    We used hyperpolarized 129Xe NMR to measure pulmonary alveolar surface area per unit gas volume SA/Vgas, alveolar septal thickness h and capillary transit time τ, three critical determinants of the lung's primary role as a gas exchange organ. An analytical solution for a simplified diffusion model is described, together with a modification of the xenon transfer contrast imaging technique utilizing 90° radio-frequency pulses applied to the dissolved phase, rather than traditional 180° pulses. With this approach, three-dimensional (3D) maps of SA/Vgas were obtained. We measured global SA/Vgas, h and τ in four normal subjects, two subjects with mild interstitial lung disease (ILD) and two subjects with mild chronic obstructive pulmonary disease (COPD). In normals, SA/Vgas decreased with increasing lung volume from ~320 to 80 cm-1 both h~13 μm and τ~1.5 s were relatively constant. For the two ILD subjects, h was, respectively, 36 and 97% larger than normal, quantifying an increased gas/blood tissue barrier; SA/Vgas and τ were normal. The two COPD subjects had SA/Vgas values ~25% that of normals, quantifying septal surface loss in emphysema; h and τ were normal. These are the first noninvasive, non-radiation-based, quantitative measurements of h and τ in patients with pulmonary disease.

  4. Green tea polyphenol extract attenuates lung injury in experimental model of carrageenan-induced pleurisy in mice

    PubMed Central

    Di Paola, Rosanna; Mazzon, Emanuela; Muià, Carmelo; Genovese, Tiziana; Menegazzi, Marta; Zaffini, Raffaela; Suzuki, Hisanory; Cuzzocrea, Salvatore

    2005-01-01

    Here we investigate the effects of the green tea extract in an animal model of acute inflammation, carrageenan-induced pleurisy. We report here that green tea extract (given at 25 mg/kg i.p. bolus 1 h prior to carrageenan), exerts potent anti-inflammatory effects in an animal model of acute inflammation in vivo. Injection of carrageenan (2%) into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and increased production of nitrite/nitrate, tumour necrosis factor alpha. All parameters of inflammation were attenuated by green tea extract treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecule ICAM-1, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) formation, as determined by immunohistochemical analysis of lung tissues. Staining for the ICAM-1, nitrotyrosine, and PARS was reduced by green tea extract. Our results clearly demonstrate that treatment with green tea extract exerts a protective effect and offers a novel therapeutic approach for the management of lung injury. PMID:15987519

  5. Beneficial effects of Red Light-Emitting Diode treatment in experimental model of acute lung injury induced by sepsis.

    PubMed

    Costa, Silvia Goes; Barioni, Éric Diego; Ignácio, Aline; Albuquerque, Juliana; Câmara, Niels Olsen Saraiva; Pavani, Christiane; Vitoretti, Luana Beatriz; Damazo, Amílcar Sabino; Farsky, Sandra Helena Poliselli; Lino-Dos-Santos-Franco, Adriana

    2017-10-04

    Sepsis is a severe disease with a high mortality index and it is responsible for the development of acute lung injury (ALI). We evaluated the effects of light-emitting diode (LED) on ALI induced by sepsis. Balb-c mice were injected with lipopolysaccharide or saline and then irradiated or not with red LED on their tracheas and lungs for 150 s, 2 and 6 h after LPS injections. The parameters were investigated 24 h after the LPS injections. Red LED treatment reduced neutrophil influx and the levels of interleukins 1β, 17 A and, tumor necrosis factor-α; in addition to enhanced levels of interferon γ in the bronchoalveolar fluid. Moreover, red LED treatment enhanced the RNAm levels of IL-10 and IFN-γ. It also partially reduced the elevated oxidative burst and enhanced apoptosis, but it did not alter the translocation of nuclear factor κB, the expression of toll-like receptor 4 (TLR4), as well as, oedema or mucus production in their lung tissues. Together, our data has shown the beneficial effects of short treatment with LED on ALI that are caused by gram negative bacterial infections. It is suggested that LED applications are an inexpensive and non-invasive additional treatment for sepsis.

  6. Green tea polyphenol extract attenuates lung injury in experimental model of carrageenan-induced pleurisy in mice.

    PubMed

    Di Paola, Rosanna; Mazzon, Emanuela; Muià, Carmelo; Genovese, Tiziana; Menegazzi, Marta; Zaffini, Raffaela; Suzuki, Hisanory; Cuzzocrea, Salvatore

    2005-06-29

    Here we investigate the effects of the green tea extract in an animal model of acute inflammation, carrageenan-induced pleurisy. We report here that green tea extract (given at 25 mg/kg i.p. bolus 1 h prior to carrageenan), exerts potent anti-inflammatory effects in an animal model of acute inflammation in vivo. Injection of carrageenan (2%) into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and increased production of nitrite/nitrate, tumour necrosis factor alpha. All parameters of inflammation were attenuated by green tea extract treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecule ICAM-1, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) formation, as determined by immunohistochemical analysis of lung tissues. Staining for the ICAM-1, nitrotyrosine, and PARS was reduced by green tea extract. Our results clearly demonstrate that treatment with green tea extract exerts a protective effect and offers a novel therapeutic approach for the management of lung injury.

  7. An experimental study of interstitial lung tissue classification in HRCT images using ANN and role of cost functions

    NASA Astrophysics Data System (ADS)

    Dash, Jatindra K.; Kale, Mandar; Mukhopadhyay, Sudipta; Khandelwal, Niranjan; Prabhakar, Nidhi; Garg, Mandeep; Kalra, Naveen

    2017-03-01

    In this paper, we investigate the effect of the error criteria used during a training phase of the artificial neural network (ANN) on the accuracy of the classifier for classification of lung tissues affected with Interstitial Lung Diseases (ILD). Mean square error (MSE) and the cross-entropy (CE) criteria are chosen being most popular choice in state-of-the-art implementations. The classification experiment performed on the six interstitial lung disease (ILD) patterns viz. Consolidation, Emphysema, Ground Glass Opacity, Micronodules, Fibrosis and Healthy from MedGIFT database. The texture features from an arbitrary region of interest (AROI) are extracted using Gabor filter. Two different neural networks are trained with the scaled conjugate gradient back propagation algorithm with MSE and CE error criteria function respectively for weight updation. Performance is evaluated in terms of average accuracy of these classifiers using 4 fold cross-validation. Each network is trained for five times for each fold with randomly initialized weight vectors and accuracies are computed. Significant improvement in classification accuracy is observed when ANN is trained by using CE (67.27%) as error function compared to MSE (63.60%). Moreover, standard deviation of the classification accuracy for the network trained with CE (6.69) error criteria is found less as compared to network trained with MSE (10.32) criteria.

  8. Angle-Resolved Photoelectron Spectrometry Studies of the Autoionization of the 2s{sup 2}2p {sup 2}P Triply Excited State of Atomic Lithium: Experimental Results and R -Matrix Calculations

    SciTech Connect

    Diehl, S.; Cubaynes, D.; Zhou, H. L.; VoKy, L.; Wuilleumier, F. J.; Kennedy, E. T.; Bizau, J. M.; Manson, S. T.; Morgan, T. J.; Blancard, C.

    2000-02-21

    We have measured the angle-resolved energy dependence of the electrons emitted over the energy range of the triply excited 2s{sup 2}2p P{sup 2} lithium resonance using synchrotron radiation. We have also calculated the behavior of the angular distribution parameter {beta} using the R -matrix approximation. Experimental and theoretical results are in good agreement and show deep minima in the 1s2p P{sup 1,} {sup 3} ionic channels. The energy at which the minima occur does not coincide with the resonance energy, but is shifted towards higher energy. (c) 2000 The American Physical Society.

  9. Manual Ventilation and Sustained Lung Inflation in an Experimental Model: Influence of Equipment Type and Operator’s Training

    PubMed Central

    Mascaretti, Renata Suman; Vale, Luciana Assis; Haddad, Luciana Branco

    2016-01-01

    Aim To compare the influence of devices for manual ventilation and individual experience on the applied respiratory mechanics and sustained lung inflation. Methods A total of 114 instructors and non-instructors from the Neonatal Resuscitation Program of the Brazilian Society of Pediatrics participated in this study. Participants ventilated an intubated manikin. To evaluate respiratory mechanics and sustained lung inflation parameters, a direct comparison was made between the self-inflating bag and the T-shaped resuscitator (T-piece), followed by an analysis of the effectiveness of the equipment according to the participants’ education and training. Results A difference between equipment types was observed for the tidal volume, with a median (interquartile range) of 28.5 mL (12.6) for the self-inflating bag and 20.1 mL (8.4) for the T-piece in the instructor group and 31.6 mL (14) for the self-inflating bag and 22.3 mL (8.8) for the T-piece in the non-instructor group. Higher inspiratory time values were observed with the T-piece in both groups of professionals, with no significant difference between them. The operator’s ability to maintain the target pressure over the 10 seconds of sustained lung inflation was evaluated using the area under the pressure-time curve and was 1.7-fold higher with the use of the T-piece. Inspiratory pressure and mean airway pressure applied during sustained lung inflation were greater with the self-inflating bag, as evaluated between the beginning and the end of the procedure. Conclusion The T-piece resulted in lower tidal volume and higher inspiratory time values, irrespective of the operator’s experience, and increased the ease of performing the sustained lung inflation maneuver, as demonstrated by the maintenance of target pressure for the desired period and a higher mean airway pressure than that obtained using the self-inflating bag. PMID:26859896

  10. Albumin nanocapsules containing fenretinide: pre-clinical evaluation of cytotoxic activity in experimental models of human non-small cell lung cancer.

    PubMed

    Pignatta, Sara; Orienti, Isabella; Falconi, Mirella; Teti, Gabriella; Arienti, Chiara; Medri, Laura; Zanoni, Michele; Carloni, Silvia; Zoli, Wainer; Amadori, Dino; Tesei, Anna

    2015-02-01

    The present study deals with the preparation of albumin nanocapsules containing fenretinide and their evaluation in experimental models of human non-small cell lung cancer. These nanocapsules showed enhanced antitumor activity with respect to free fenretinide due to the solubilization effect of albumin on the hydrophobic drug, known to improve bioavailability. The high expression of caveolin-1 on the A549 cell surface further enhanced the antitumor activity of the nanoencapsulated fenretinide. Caveolin-1 favored albumin uptake and improved the efficacy of the fenretinide-loaded albumin nanocapsules, especially in 3-D cultures where the densely packed 3-D structures impaired drug diffusibility and severely reduced the activity of the free drug. The efficacy of the fenretinide albumin nanocapsules was further confirmed in tumor xenograft models of A549 by the significant delay in tumor progression observed with respect to control after intravenous administration of the novel formulation. This study describes the preparation of fenretinide containing albumin nanocapsules and their evaluation in experimental models of non-small cell lung cancer, showing enhanced antitumor activity compared to free fenretinide. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension: an experimental study in a lavage model of lung injury

    PubMed Central

    2012-01-01

    Introduction It is well established that during mechanical ventilation of patients with acute respiratory distress syndrome cyclic recruitment/derecruitment and overdistension are potentially injurious for lung tissues. We evaluated whether the forced oscillation technique (FOT) could be used to guide the ventilator settings in order to minimize cyclic lung recruitment/derecruitment and cyclic mechanical stress in an experimental model of acute lung injury. Methods We studied six pigs in which lung injury was induced by bronchoalveolar lavage. The animals were ventilated with a tidal volume of 6 ml/kg. Forced oscillations at 5 Hz were superimposed on the ventilation waveform. Pressure and flow were measured at the tip and at the inlet of the endotracheal tube respectively. Respiratory system reactance (Xrs) was computed from the pressure and flow signals and expressed in terms of oscillatory elastance (EX5). Positive end-expiratory pressure (PEEP) was increased from 0 to 24 cm H2O in steps of 4 cm H2O and subsequently decreased from 24 to 0 in steps of 2 cm H2O. At each PEEP step CT scans and EX5 were assessed at end-expiration and end-inspiration. Results During deflation the relationship between both end-expiratory and end-inspiratory EX5 and PEEP was a U-shaped curve with minimum values at PEEP = 13.4 ± 1.0 cm H2O (mean ± SD) and 13.0 ± 1.0 cm H2O respectively. EX5 was always higher at end-inspiration than at end-expiration, the difference between the average curves being minimal at 12 cm H2O. At this PEEP level, CT did not show any substantial sign of intra-tidal recruitment/derecruitment or expiratory lung collapse. Conclusions Using FOT it was possible to measure EX5 both at end-expiration and at end-inspiration. The optimal PEEP strategy based on end-expiratory EX5 minimized intra-tidal recruitment/derecruitment as assessed by CT, and the concurrent attenuation of intra-tidal variations of EX5 suggests that it may also minimize tidal mechanical stress

  12. Neonatal epithelial hypoxia inducible factor-1α expression regulates the response of the lung to experimental asthma.

    PubMed

    Greenwood, Krista K; Proper, Steven P; Saini, Yogesh; Bramble, Lori A; Jackson-Humbles, Daven N; Wagner, James G; Harkema, Jack R; LaPres, John J

    2012-03-01

    Allergic airway disease is characterized by a T helper type 2 cell-mediated airway inflammation and airway hyperresponsiveness. Little is known about the role of hypoxia-mediated signaling in the progression of the disease. To address this knowledge gap, a mouse model was created in which doxycycline exposure induces the functional deletion of hypoxia inducible factor-1α from alveolar type II and Clara cells of the lung. When hypoxia inducible factor-1α deletion was induced during the early postnatal development period of the lung, the mice displayed an enhanced response to the ovalbumin model of allergic airway disease. These hypoxia inducible factor-1α-deficient mice exhibit increased cellular infiltrates, eosinophilia in the lavage fluid and parenchyma, and T helper type 2 cytokines, as compared with ovalbumin-treated control mice. Moreover, these hypoxia inducible factor-1α-deficient mice display increased airway resistance when compared with their control counterparts. Interestingly, if the loss of hypoxia inducible factor-1α was induced in early adulthood, the exacerbated phenotype was not observed. Taken together, these results suggest that epithelial hypoxia inducible factor-1α plays an important role in establishing the innate immunity of the lung and epithelial-specific deficiency in the transcription factor, during early postnatal development, increases the severity of inflammation and functional airway resistance, following ovalbumin challenge. Finally, these results might explain some of the chronic respiratory pathology observed in premature infants, especially those that receive supplemental oxygen. This early hyperoxic exposure, from normal ambient and supplemental oxygen, would presumably inhibit normal hypoxia inducible factor-1α signaling, mimicking the functional deletion described.

  13. Neonatal epithelial hypoxia inducible factor-1α expression regulates the response of the lung to experimental asthma

    PubMed Central

    Greenwood, Krista K.; Proper, Steven P.; Saini, Yogesh; Bramble, Lori A.; Jackson-Humbles, Daven N.; Wagner, James G.; Harkema, Jack R.

    2012-01-01

    Allergic airway disease is characterized by a T helper type 2 cell-mediated airway inflammation and airway hyperresponsiveness. Little is known about the role of hypoxia-mediated signaling in the progression of the disease. To address this knowledge gap, a mouse model was created in which doxycycline exposure induces the functional deletion of hypoxia inducible factor-1α from alveolar type II and Clara cells of the lung. When hypoxia inducible factor-1α deletion was induced during the early postnatal development period of the lung, the mice displayed an enhanced response to the ovalbumin model of allergic airway disease. These hypoxia inducible factor-1α-deficient mice exhibit increased cellular infiltrates, eosinophilia in the lavage fluid and parenchyma, and T helper type 2 cytokines, as compared with ovalbumin-treated control mice. Moreover, these hypoxia inducible factor-1α-deficient mice display increased airway resistance when compared with their control counterparts. Interestingly, if the loss of hypoxia inducible factor-1α was induced in early adulthood, the exacerbated phenotype was not observed. Taken together, these results suggest that epithelial hypoxia inducible factor-1α plays an important role in establishing the innate immunity of the lung and epithelial-specific deficiency in the transcription factor, during early postnatal development, increases the severity of inflammation and functional airway resistance, following ovalbumin challenge. Finally, these results might explain some of the chronic respiratory pathology observed in premature infants, especially those that receive supplemental oxygen. This early hyperoxic exposure, from normal ambient and supplemental oxygen, would presumably inhibit normal hypoxia inducible factor-1α signaling, mimicking the functional deletion described. PMID:22180657

  14. Comparison of the rate constants for energy transfer in the light-harvesting protein, C-phycocyanin, calculated from Foerster`s theory and experimentally measured by time-resolved fluorescence spectroscopy

    SciTech Connect

    Debreczeny, Martin Paul

    1994-05-01

    We have measured and assigned rate constants for energy transfer between chromophores in the light-harvesting protein C-phycocyanin (PC), in the monomeric and trimeric aggregation states, isolated from Synechococcus sp. PCC 7002. In order to compare the measured rate constants with those predicted by Fdrster`s theory of inductive resonance in the weak coupling limit, we have experimentally resolved several properties of the three chromophore types ({beta}{sub 155} {alpha}{sub 84}, {beta}{sub 84}) found in PC monomers, including absorption and fluorescence spectra, extinction coefficients, fluorescence quantum yields, and fluorescence lifetimes. The cpcB/C155S mutant, whose PC is missing the {beta}{sub 155} chromophore, was, useful in effecting the resolution of the chromophore properties and in assigning the experimentally observed rate constants for energy transfer to specific pathways.

  15. Protective effects of Trifolium alexandrinum L. against lung injury induced by environmental toxin CCl4 in experimental rats

    PubMed Central

    Khan, Rahmat Ali; Alkreathy, Huda Mohammad; Saboorshah, Abdus; Ahmed, Mushtaq; Khan, Samiullah

    2016-01-01

    Background In Pakistan numerous medicinal floras has used in the treatment of various human ailments. Among them Trifolium alexandrinum L. is traditionally used in the curing of disease. Presently we designed to ascertain the protective role of Trifolium alexandrinum methanolic extracts (TAME) against carbon tetrachloride (CCl4)-induced lung injury and oxidative stress in rats. Methods Exposure to CCl4 induces oxidative stress and causes tissue damage by the induction of CCl4 free radicals. Twenty-four male albino rats were divided equally into four groups. Rats in group I had free access to drinking water and laboratory food. Group II was treated with 1 ml/kg body weight (b.w.) CCl4 (30% in olive oil). Groups III and IV rats were fed (p.o.) 200 mg/kg b.w. TAME and 50 mg/kg b.w. silymarin after 24 h of CCl4 treatment for 2 weeks. Results Administration of CCl4 caused a significant (p<0.01) decrease in the activities of antioxidant enzymes (catalase, peroxidase, glutathione peroxidase, glutathione-S-transferase), and glutathione contents were decreased; however, thiobarbituric acid-reactive substances were increased (p<0.01). The alterations caused by CCl4 were significantly (p<0.01) reversed toward control levels by supplementation of TAME and silymarin. Conclusion These results suggest that in rats TAME and silymarin could protect the lungs against CCl4-induced oxidative damage. PMID:27834184

  16. Relevance of maintenance triple-drug immunosuppression to bridle the amplification of rat cytomegalovirus infection after experimental lung transplantation.

    PubMed

    Lehle, K; von Suesskind-Schwendi, M; Diez, C; Michl, M; Geissler, E K; Wottge, H U; Schmid, C; Hirt, S W

    2012-12-01

    Immunosuppressive therapy required to treat rejection after lung transplantation (LTx) contributes significantly to the pathogenesis of cytomegalovirus (CMV) infection and disease. In a weak allogeneic left LTx model in the rat (Fisher 344 [F344] to Wistar Kyoto [WKY] rats) we analyzed the influence of acute CMV infection on postoperative day (POD) 3, with application of standard triple-drug immunosuppression (TD-IS) (cyclosporin A, azathioprine, prednisolone) on late outcome after LTx. Native right lungs and syngeneic grafts (WKY to WKY) served as controls. Rats were sacrificed on POD 15, 30, 60, and 100. TD-IS completely prevented acute and chronic rejection in non-infected rats. Allografts of CMV-infected rats treated with TD-IS showed only mild perivascular infiltrations in 6/10 rats (POD 15 and 30), which persisted up to POD 100 in 4/10 rats. In the long-term course, mild isolated interstitial and alveolar changes were found in 40% of these animals. In conclusion, rat CMV infection partially neutralized the immunosuppressive effect of TD-IS. However, an amplification of CMV infection under TD-IS can be controlled and does not result in fatal outcome.

  17. The complete, temperature resolved experimental spectrum of methanol (CH{sub 3}OH) between 214.6 and 265.4 GHz

    SciTech Connect

    McMillan, James P.; Fortman, Sarah M.; Neese, Christopher F.; De Lucia, Frank C.

    2014-11-01

    The spectrum of methanol (CH{sub 3}OH) has been characterized between 214.6 and 265.4 GHz for astrophysically significant temperatures. Four hundred and eighty-six spectra with absolute intensity calibration recorded between 240 and 389 K provided a means for the calculation of the complete experimental spectrum (CES) of methanol as a function of temperature. The CES includes contributions from v{sub t} = 3 and other higher states that are difficult to model quantum mechanically (QM). It also includes the spectrum of the {sup 13}C isotopologue in terrestrial abundance. In general the QM models provide frequencies that are within 1 MHz of their experimental values, but there are several outliers that differ by tens of MHz. As in our recent work on methanol in the 560-654 GHz region, significant intensity differences between our experimental intensities and cataloged values were found. In this work these differences are explored in the context of several QM analyses. The experimental results presented here are analyzed to provide a frequency point-by-point catalog that is well suited for the simulation of crowded and overlapped spectra. Additionally, a catalog in the usual line frequency, line strength, and lower state energy format is provided.

  18. Resolvability of positron decay channels

    SciTech Connect

    Fluss, M.J.; Howell, R.H.; Rosenberg, I.J.; Meyer, P.

    1985-03-07

    Many data analysis treatments of positron experiments attempt to resolve two or more positron decay or exist channels which may be open simultaneously. Examples of the need to employ such treatments of the experimental results can be found in the resolution of the constituents of a defect ensemble, or in the analysis of the complex spectra which arise from the interaction of slow positrons at or near the surfaces of solids. Experimental one- and two-dimensional angular correlation of annihilation radiation experiments in Al single crystals have shown that two defect species (mono- and divacancies) can be resolved under suitable conditions. Recent experiments at LLNL indicate that there are a variety of complex exit channels open to positrons interacting at surfaces, and ultimely these decay channels must also be suitably resolved from one another. 6 refs., 4 figs.

  19. Effects of Blood Flow and/or Ventilation Restriction on Radiofrequency Coagulation Size in the Lung: An Experimental Study in Swine

    SciTech Connect

    Anai, Hiroshi; Uchida, Barry T.; Pavcnik, Dusan Seong, Chang Kyu; Baker, Phillip; Correa, Luiz Otavio; Corless, Christopher L.; Sakaguchi, Hiroshi; Kichikawa, Kimihiko; Keller, Frederick S.; Roesch, Josef

    2006-10-15

    lung parenchyma is increased by ventilation and particularly by pulmonary artery blood flow restriction. The value of these restrictions for potential clinical use needs to be explored in experimentally induced lung tumors.

  20. Effect of lung flooding and high-intensity focused ultrasound on lung tumours: an experimental study in an ex vivo human cancer model and simulated in vivo tumours in pigs

    PubMed Central

    2014-01-01

    Background High-intensity focused ultrasound is a valuable tool for minimally invasive tumour ablation. However, due to the air content in ventilated lungs, lung tumours have never been treated with high-intensity focused ultrasound. Lung flooding enables efficient lung sonography and tumour imaging in ex vivo human and in vivo porcine lung cancer models. The current study evaluates the effectiveness of lung flooding and sonography-guided high-intensity focused ultrasound for lung tumour ablation in ex vivo human and in vivo animal models. Methods Lung flooding was performed in four human lung lobes which were resected from non-small cell lung cancers. B-mode imaging and temperature measurements were simultaneously obtained during high-intensity focused ultrasonography of centrally located lung cancers. The tumour was removed immediately following insonation and processed for nicotinamide adenine dinucleotide phosphate-diaphorase and H&E staining. In addition, the left lungs of three pigs were flooded. Purified BSA in glutaraldehyde was injected centrally into the left lower lung lobe to simulate a lung tumour. The ultrasound was focused transthoracically through the flooded lung into the simulated tumour with the guidance of sonography. The temperature of the tumour was simultaneously measured. The vital signs of the animal were monitored during the procedure. Results A well-demarcated lesion of coagulation necrosis was produced in four of four human lung tumours. There did not appear to be any damage to the surrounding lung parenchyma. After high-intensity focused ultrasound insonation, the mean temperature increase was 7.5-fold higher in the ex vivo human tumour than in the flooded lung tissue (52.1 K ± 8.77 K versus 7.1 K ± 2.5 K). The transthoracic high-intensity focused ultrasound of simulated tumours in the in vivo model resulted in a mean peak temperature increase up to 53.7°C (±4.5). All of the animals survived the procedure without

  1. Lung Transplant

    MedlinePlus

    Lung transplant Overview By Mayo Clinic Staff A lung transplant is a surgical procedure to replace a diseased or ... lung, usually from a deceased donor. A lung transplant is reserved for people who have tried other ...

  2. Lung surgery

    MedlinePlus

    ... lung tissue that is diseased or damaged from emphysema or bronchiectasis Remove blood or blood clots ( hemothorax ) ... Editorial team. Related MedlinePlus Health Topics Collapsed Lung Emphysema Lung Cancer Lung Diseases Pleural Disorders Browse the ...

  3. Lung Emergencies

    MedlinePlus

    ... Emergencies Cardiac Emergencies Eye Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at ... should be considered an emergency. Symptoms of sudden lung collapse (pneumothorax) Symptoms of a sudden lung collapse ...

  4. Lung Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Lung Cancer What is Lung Cancer? How Tumors Form The body is made ... button on your keyboard.) Two Major Types of Lung Cancer There are two major types of lung ...

  5. Deposition efficiency of inhaled particles (15-5000 nm) related to breathing pattern and lung function: an experimental study in healthy children and adults.

    PubMed

    Rissler, Jenny; Gudmundsson, Anders; Nicklasson, Hanna; Swietlicki, Erik; Wollmer, Per; Löndahl, Jakob

    2017-04-08

    Exposure to airborne particles has a major impact on global health. The probability of these particles to deposit in the respiratory tract during breathing is essential for their toxic effects. Observations have shown that there is a substantial variability in deposition between subjects, not only due to respiratory diseases, but also among individuals with healthy lungs. The factors determining this variability are, however, not fully understood. In this study we experimentally investigate factors that determine individual differences in the respiratory tract depositions of inhaled particles for healthy subjects at relaxed breathing. The study covers particles of diameters 15-5000 nm and includes 67 subjects aged 7-70 years. A comprehensive examination of lung function was performed for all subjects. Principal component analyses and multiple regression analyses were used to explore the relationships between subject characteristics and particle deposition. A large individual variability in respiratory tract deposition efficiency was found. Individuals with high deposition of a certain particle size generally had high deposition for all particles <3500 nm. The individual variability was explained by two factors: breathing pattern, and lung structural and functional properties. The most important predictors were found to be breathing frequency and anatomical airway dead space. We also present a linear regression model describing the deposition based on four variables: tidal volume, breathing frequency, anatomical dead space and resistance of the respiratory system (the latter measured with impulse oscillometry). To understand why some individuals are more susceptible to airborne particles we must understand, and take into account, the individual variability in the probability of particles to deposit in the respiratory tract by considering not only breathing patterns but also adequate measures of relevant structural and functional properties.

  6. Experimental Study on How Human Lung Surfactant Protein SP-B1-25 is Oxidized by Ozone in the Presence of Fe(II) and Ascorbic Acid

    NASA Astrophysics Data System (ADS)

    Colussi, A. J.; Enami, S.; Hoffmann, M. R.

    2014-12-01

    We will report the results of experiments on the chemical fate of the human lung surfactant protein SP-B1-25 upon exposure to gaseous ozone in realistic aqueous media simulating the conditions prevalent in epithelial lining fluids in polluted ambient air. Our experiments consist of exposing aqueous microjets containing SP-B1-25, the natural antioxidant ascorbic acid, and the Fe2+ carried by most atmospheric fine particulates, under mild acidic conditions, such as those created by the innate lung host defense response. Reactants and the products of such interactions are detected via online electrospray ionization mass spectrometry. We will show that ascorbic acid largely inhibits the ozonation of SP-B1-25 in the absence of Fe2+, leading to the formation of an ascorbic acid ozonide (Enami et al., PNAS 2008). In the presence of Fe2+, however, the ozonide decomposes into reactive intermediates that result in the partial oxidation of SP-B1-25, presumable affecting its function as surfactant. We infer that these experimental results establish a plausible causal link for the observed synergic adverse health effects of ambient ozone and fine particulates

  7. Increased expression of host iron-binding proteins precedes iron accumulation and calcification of primary lung lesions in experimental tuberculosis in the guinea pig

    PubMed Central

    Basaraba, Randall J.; Bielefeldt-Ohmann, Helle; Eschelbach, Ellie K.; Reisenhauer, Claire; Tolnay, Airn E.; C.Taraba, Lauren; Shanley, Crystal A.; Smith, Erin A.; Bedwell, Cathy L.; Chlipala, Elizabeth A.; Orme, Ian M.

    2008-01-01

    The growth and virulence of Mycobacterium tuberculosis depends on its ability to scavenge host iron, an essential and limited micronutrient in vivo. In this study we show that ferric iron accumulates both intra- and extra-cellularly in the primary lung lesions of guinea pigs aerosol-infected with the H37Rv strain of Mycobacterium tuberculosis. Iron accumulated within macrophages at the periphery of the primary granulomatous lesions while extra-cellular ferric iron was concentrated in areas of lesion necrosis. Accumulation of iron within primary lesions was preceded by an increase in expression of heavy chain (H) ferritin, lactoferrin and receptors for transferrin, primarily by macrophages and granulocytes. The increased expression of intra-cellular H ferritin and extra-cellular lactoferrin, more so than transferrin receptor, paralleled the development of necrosis within primary lesions. The deposition of extra-cellular ferric iron within necrotic foci coincided with the accumulation of calcium and phosphorus and other cations in the form of dystrophic calcification. Primary lung lesions from guinea pigs vaccinated with Mycobactrium bovis BCG prior to experimental infection, had reduced iron accumulation as well as H ferritin, lactoferrin and transferrin receptor expression. The amelioration of primary lesion necrosis and dystrophic calcification by BCG vaccination was coincident with the lack of extra-cellular ferric iron and lactoferrin accumulation. These data demonstrate that BCG vaccination ameliorates primary lesion necrosis, dystrophic mineralization and iron accumulation, in part by down-regulating the expression of macrophage H ferritin, lactoferrin and transferrin receptors, in vivo. PMID:17942369

  8. Lung cancer

    SciTech Connect

    Aisner, J.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer.

  9. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by (99m)Tc-MDP bone scintigraphy.

    PubMed

    Yang, Shunfang; Dong, Qianggang; Yao, Ming; Shi, Meiping; Ye, Jianding; Zhao, Langxiang; Su, Jianzhong; Gu, Weiyong; Xie, Wenhui; Wang, Kankan; Du, Yanzhi; Li, Yao; Huang, Yan

    2009-04-01

    Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with (99m)Tc-MDP bone scintigraphy. The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with (99m)Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as an accurate, sensitive, noninvasive tool to detect

  10. Distribution of porcine monocytes in different lymphoid tissues and the lungs during experimental Actinobacillus pleuropneumoniae infection and the role of chemokines

    PubMed Central

    2013-01-01

    Monocytes play an essential role in the defense against bacterial pathogens. Bone marrow (BM) and peripheral blood (PB) monocytes in pigs consist of the main “steady-state” subpopulations: CD14hi/CD163-/SLA-DR- and CD14low/CD163+/SLA-DR+. During inflammation, the subpopulation of “inflammatory” monocytes expressing very high levels of CD163, but lacking the SLA-DR molecule (being CD14low/CD163+/SLA-DR-) appears in the BM and PB and replaces the CD14low/CD163+/SLA-DR+ subpopulation. However, current knowledge of monocyte migration into inflamed tissues in pigs is limited. The aim of the present study was to evaluate the distribution of “inflammatory” CD14low/CD163+/SLA-DR- monocytes during experimental inflammation induced by Actinobacillus pleuropneumoniae (APP) and a possible role for chemokines in attracting “inflammatory” CD14low/CD163+/SLA-DR- monocytes into the tissues. Monocyte subpopulations were detected by flow cytometry. Chemokines and chemokine receptors were detected by RT-qPCR. The “steady-state” monocytes were found in the BM, PB, spleen and lungs of control pigs. After APP-infection, “inflammatory” monocytes replaced the “steady-state” subpopulation in BM, PB, spleen and moreover, they appeared in an unaffected area, demarcation zone and necrotic area of the lungs and in tracheobronchial lymph nodes. They did not appear in mesenteric lymph nodes. Levels of mRNA for various chemokines with their appropriate receptors were found to be elevated in BM (CCL3-CCR1/CCR5, CCL8-CCR2/CCR5, CCL19-CCR7), necrotic area of the lungs (CCL3-CCR1, CCL5-CCR1/CCR3, CCL11-CCR3, CCL22/CCR4) and tracheobronchial lymph nodes (CCL3-CCR1) and therefore they could play a role in attracting monocytes into inflamed tissues. In conclusion, “inflammatory” monocytes appear in different lymphoid tissues and the lungs after APP infection in pigs. Various chemokines could drive this process. PMID:24134635

  11. Enhancement of antitumor effect of paclitaxel in combination with immunomodulatory Withania somnifera on benzo(a)pyrene induced experimental lung cancer.

    PubMed

    Senthilnathan, Palaniyandi; Padmavathi, Radhakrishnan; Banu, Syed Mumtaz; Sakthisekaran, Dhanapal

    2006-02-25

    The current experimental work deals with the immunomodulatory studies on the extract of Withania somnifera (L.) Dunal root powder against benzo(a)pyrene induced lung cancer in male Swiss albino mice. In our previous study, we reported the antioxidant and anticarcinogenic effect of W. somnifera (L.) Dunal along with paclitaxel. Immune dysfunction has been found to be associated with cancer and chemotherapy. Benzo(a)pyrene induced cancer animals were treated with 400mg/kg bodyweight of W. somnifera (L.) Dunal extract for 30 days significantly alters the levels of immunocompetent cells, immune complexes and immunoglobulins. Based on the data, the carcinogen as well as the paclitaxel affects the immune system, the toxic side effects on the immune system is more reversible and more controllable by W. somnifera (L.) Dunal. These results concluded the immunomodulatory activity of W. somnifera (L.) Dunal extract, which is a known immunomodulator in indigenous medicine.

  12. Collisional quenching of OD A 2Σ+ by H2: experimental and theoretical studies of the state-resolved OD X 2Π product distribution and branching fraction.

    PubMed

    Lehman, Julia H; Dempsey, Logan P; Lester, Marsha I; Fu, Bina; Kamarchik, Eugene; Bowman, Joel M

    2010-10-28

    We report joint experimental and theoretical studies of outcomes resulting from the nonreactive quenching of electronically excited OD A  (2)Σ(+) by H(2). The experiments utilize a pump-probe technique to detect the OD X  (2)Π product state distribution under single collision conditions. The OD X  (2)Π products are observed primarily in their lowest vibrational state (v(") = 0) with substantially less population in v(") = 1. The OD X  (2)Π products are generated with a high degree of rotational excitation, peaking at N(") = 21 with an average rotational energy of 4600 cm(-1), and a strong propensity for populating the Π(A(')) Λ-doublet component indicative of alignment of the half-filled pπ orbital in the plane of OD rotation. Branching fraction measurements show that the nonreactive channel accounts for less than 20% of quenching outcomes. Complementary classical trajectory calculations of the postquenching dynamics are initiated from representative points along seams of conical intersections between the ground and excited-state potentials of OD(A  (2)Σ(+),X  (2)Π) + H(2). Diabatic modeling of the initial momenta in the dynamical calculations captures the key experimental trends: OD X  (2)Π products released primarily in their ground vibrational state with extensive rotational excitation and a branching ratio that strongly favors reactive quenching. The OD A  (2)Σ(+) + H(2) results are also compared with previous studies on the quenching of OH A  (2)Σ(+) + H(2); the two experimental studies show remarkably similar rotational energy distributions for the OH and OD X  (2)Π radical products.

  13. The protonation states of oxo-bridged Mn(IV) dimers resolved by experimental and computational Mn K pre-edge X-ray absorption spectroscopy.

    PubMed

    Krewald, Vera; Lassalle-Kaiser, Benedikt; Boron, Thaddeus T; Pollock, Christopher J; Kern, Jan; Beckwith, Martha A; Yachandra, Vittal K; Pecoraro, Vincent L; Yano, Junko; Neese, Frank; DeBeer, Serena

    2013-11-18

    In nature, the protonation of oxo bridges is a commonly encountered mechanism for fine-tuning chemical properties and reaction pathways. Often, however, the protonation states are difficult to establish experimentally. This is of particular importance in the oxygen evolving complex of photosystem II, where identification of the bridging oxo protonation states is one of the essential requirements toward unraveling the mechanism. In order to establish a combined experimental and theoretical protocol for the determination of protonation states, we have systematically investigated a series of Mn model complexes by Mn K pre-edge X-ray absorption spectroscopy. An ideal test case for selective bis-μ-oxo-bridge protonation in a Mn dimer is represented by the system [Mn(IV)2(salpn)2(μ-OHn)2](n+). Although the three species [Mn(IV)2(salpn)2(μ-O)2], [Mn(IV)2(salpn)2(μ-O)(μ-OH)](+) and [Mn(IV)2(salpn)2(μ-OH)2](2+) differ only in the protonation of the oxo bridges, they exhibit distinct differences in the pre-edge region while maintaining the same edge energy. The experimental spectra are correlated in detail to theoretically calculated spectra. A time-dependent density functional theory approach for calculating the pre-edge spectra of molecules with multiple metal centers is presented, using both high spin (HS) and broken symmetry (BS) electronic structure solutions. The most intense pre-edge transitions correspond to an excitation of the Mn 1s core electrons into the unoccupied orbitals of local e(g) character (d(z)(2) and d(xy) based in the chosen coordinate system). The lowest energy experimental feature is dominated by excitations of 1s-α electrons, and the second observed feature is primarily attributed to 1s-β electron excitations. The observed energetic separation is due to spin polarization effects in spin-unrestricted density functional theory and models final state multiplet effects. The effects of spin polarization on the calculated Mn K pre-edge spectra, in

  14. Host-parasite relationships in experimental airborne tuberculosis. V. Lack of hematogenous dissemination of Mycobacterium tuberculosis to the lungs in animals vaccinated with Bacille Calmette-Guérin.

    PubMed

    Fok, J S; Ho, R S; Arora, P K; Harding, G E; Smith, D W

    1976-02-01

    The influence of bacille Calmette-Guérin (BCG) on the pathogenesis of experimental airborne tuberculosis was studied. In a model that approximates the conditions under which man is vaccinated and infected, BCG-vaccinated and unvaccinated guinea pigs were infected by the respiratory route with an inoculum that resulted in the inhalation and retention (by each animal) of approximately three virulent tubercle bacilli (Mycobacterium tuberculosis strain H37Rv). Hematogenous seeding of the lungs occurred in unvaccinated animals about three weeks after aerosol infection but did not occur in BCG-vaccinated animals. Furthermore, the lungs of BCG-vaccinated animals failed to kill H37Rv that was introduced intravenously; however, evidence of mycobacteriostatic activity was found throughout the lungs. In view of the importance of hematogenous dissemination to the apex of the lungs in the establishment of pulmonary tuberculosis in man, the foregoing observations suggest a means by which vaccination with BCG may confer acquired resistance to tuberculosis.

  15. Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel

    PubMed Central

    Lee, Ho Jeong; Hanibuchi, Masaki; Kim, Sun-Jin; Yu, Hyunkyung; Kim, Mark Seungwook; He, Junqin; Langley, Robert R.; Lehembre, François; Regenass, Urs; Fidler, Isaiah J.

    2016-01-01

    Background We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. Methods The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non–small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. Results Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. Conclusions Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases. PMID:26995790

  16. Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel.

    PubMed

    Lee, Ho Jeong; Hanibuchi, Masaki; Kim, Sun-Jin; Yu, Hyunkyung; Kim, Mark Seungwook; He, Junqin; Langley, Robert R; Lehembre, François; Regenass, Urs; Fidler, Isaiah J

    2016-04-01

    We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved

  17. Vibrationally resolved NEXAFS at C and N K-edges of pyridine, 2-fluoropyridine and 2,6-difluoropyridine: A combined experimental and theoretical assessment

    SciTech Connect

    Baiardi, Alberto; Mendolicchio, Marco; Barone, Vincenzo; Fronzoni, Giovanna; Cardenas Jimenez, Gustavo Adolfo; Stener, Mauro; Grazioli, Cesare; Simone, Monica de; Coreno, Marcello

    2015-11-28

    In the present work, the near edge X-ray absorption spectroscopy (NEXAFS) spectra at both C and N K-edges of pyridine, 2-fluoropyridine, and 2,6-difluoropyridine have been studied both experimentally and theoretically. From an electronic point of view, both transition potential density functional theory and time-dependent density functional theory approaches lead to reliable results provided that suitable basis sets and density functionals are employed. In this connection, the global hybrid B3LYP functional in conjunction with the EPR-III basis set appears particularly suitable after constant scaling of the band positions. For the N K-edge, vertical energies obtained at these levels and broadened by symmetric Gaussian distributions provide spectra in reasonable agreement with the experiment. Vibronic contributions further modulate the band-shapes leading to a better agreement with the experimental results, but are not strictly necessary for semi-quantitative investigations. On the other hand, vibronic contributions are responsible for strong intensity redistribution in the NEXAFS C K-edge spectra, and their inclusion is thus mandatory for a proper description of experiments. In this connection, the simple vertical gradient model is particularly appealing in view of its sufficient reliability and low computational cost. For more quantitative results, the more refined vertical Hessian approach can be employed, and its effectiveness has been improved thanks to a new least-squares fitting approach.

  18. Lung carcinogenesis by tobacco smoke.

    PubMed

    Hecht, Stephen S

    2012-12-15

    Cigarette smoke is a complex mixture of chemicals including multiple genotoxic lung carcinogens. The classic mechanisms of carcinogen metabolic activation to DNA adducts, leading to miscoding and mutations in critical growth control genes, applies to this mixture but some aspects are difficult to establish because of the complexity of the exposure. This article discusses certain features of this mechanism including the role of nicotine and its receptors; lung carcinogens, co-carcinogens and related substances in cigarette smoke; structurally characterized DNA adducts in the lungs of smokers; the mutational consequences of DNA adduct formation in smokers' lungs; and biomarkers of nicotine and carcinogen uptake as related to lung cancer. While there are still uncertainties which may never be fully resolved, the general mechanisms by which cigarette smoking causes lung cancer are well understood and provide insights relevant to prevention of lung cancer, the number one cancer killer in the world, causing 1.37 million deaths per year. Copyright © 2012 UICC.

  19. Lung Carcinogenesis by Tobacco Smoke

    PubMed Central

    Hecht, Stephen S.

    2012-01-01

    Cigarette smoke is a complex mixture of chemicals including multiple genotoxic lung carcinogens. The classic mechanisms of carcinogen metabolic activation to DNA adducts, leading to miscoding and mutations in critical growth control genes, applies to this mixture but some aspects are difficult to establish because of the complexity of the exposure. This paper discusses certain features of this mechanism including the role of nicotine and its receptors; lung carcinogens, co-carcinogens and related substances in cigarette smoke; structurally characterized DNA adducts in the lungs of smokers; the mutational consequences of DNA adduct formation in smokers’ lungs; and biomarkers of nicotine and carcinogen uptake as related to lung cancer. While there are still uncertainties which may never be fully resolved, the general mechanisms by which cigarette smoking causes lung cancer are well understood and provide insights relevant to prevention of lung cancer, the number one cancer killer in the world, causing 1.37 million deaths per year. PMID:22945513

  20. THE COMPLETE, TEMPERATURE-RESOLVED EXPERIMENTAL SPECTRUM OF ETHYL CYANIDE (CH{sub 3}CH{sub 2}CN) BETWEEN 210 AND 270 GHz

    SciTech Connect

    Fortman, Sarah M.; Medvedev, Ivan R.; Neese, Christopher F.; De Lucia, Frank C.

    2010-12-20

    This paper reports the extension of a previously reported experimental method for the identification and characterization of astrophysical weeds in millimeter and submillimeter spectra to the widely used 210-270 GHz atmospheric window. At 300 K, these spectra contain contributions from approximately 40 vibrational states in addition to the cataloged ground state. The quantum mechanical analysis of such a large number of states would be a formidable challenge due to the complex interactions among these dense vibrational states. A new heterodyne receiver-based system is reported, as well as its intensity calibration. Results are presented in the standard astrophysical catalog format as well as our previously described point-by-point format that is effective for the characterization of blends. We also describe and validate an additional spectral synthesis approach, based on the much smaller line list catalog, which is useful in the blended line limit.

  1. Optimization of medical imaging display systems: using the channelized Hotelling observer for detecting lung nodules: experimental study

    NASA Astrophysics Data System (ADS)

    Platisa, Ljiljana; Vansteenkiste, Ewout; Goossens, Bart; Marchessoux, Cédric; Kimpe, Tom; Philips, Wilfried

    2009-02-01

    Medical-imaging systems are designed to aid medical specialists in a specific task. Therefore, the physical parameters of a system need to optimize the task performance of a human observer. This requires measurements of human performance in a given task during the system optimization. Typically, psychophysical studies are conducted for this purpose. Numerical observer models have been successfully used to predict human performance in several detection tasks. Especially, the task of signal detection using a channelized Hotelling observer (CHO) in simulated images has been widely explored. However, there are few studies done for clinically acquired images that also contain anatomic noise. In this paper, we investigate the performance of a CHO in the task of detecting lung nodules in real radiographic images of the chest. To evaluate variability introduced by the limited available data, we employ a commonly used study of a multi-reader multi-case (MRMC) scenario. It accounts for both case and reader variability. Finally, we use the "oneshot" methods to estimate the MRMC variance of the area under the ROC curve (AUC). The obtained AUC compares well to those reported for human observer study on a similar data set. Furthermore, the "one-shot" analysis implies a fairly consistent performance of the CHO with the variance of AUC below 0.002. This indicates promising potential for numerical observers in optimization of medical imaging displays and encourages further investigation on the subject.

  2. A further review of inhalation studies with cigarette smoke and lung cancer in experimental animals, including transgenic mice.

    PubMed

    Coggins, C R E

    2010-10-01

    The lack of an effective animal model for pulmonary carcinogenesis in smokers is a continuing problem for researchers trying to design Potentially Reduced Risk Products for those smokers who are either unwilling or unable to quit smoking. The major failing of inhalation assays with cigarette smoke in laboratory animals is that these assays produce only small percentages of animals with pulmonary tumors (e.g. adenomas, with the occasional adenocarcinoma), as opposed to the highly invasive carcinomas (e.g. small cell and squamous cell) seen in smokers. To update previous reviews on animal models, and to add different types of transgenic (Tg) mice to the review. Reviews were made of articles retrieved from PubMed and elsewhere. The addition of Tg mice to the arsenal of tests used for the evaluation of the carcinogenic potential of cigarettes did not result in any better understanding of the inability of such testing to reflect the epidemiological evidence for lung cancer in smokers. As in previous reviews on the subject, the best assay providing support for the epidemiology data is still the 5-month whole-body exposure of male A/J mice to a combination of mainstream/sidestream smoke, followed by a 4-month recovery.

  3. Protective effects of mastic oil from Pistacia lentiscus variation chia against experimental growth of lewis lung carcinoma.

    PubMed

    Magkouta, Sophia; Stathopoulos, Georgios T; Psallidas, Ioannis; Papapetropoulos, Andreas; Kolisis, Fragiskos N; Roussos, Charis; Loutrari, Heleni

    2009-01-01

    Mastic oil from Pistacia lentiscus variation chia, a traditionally used dietary flavoring agent with medicinal properties, has been shown to exert in vitro antitumor activities, but no study has addressed in vivo efficacy and mechanisms of action. Presently, we demonstrated that treatment of immunocompetent mice with mastic oil (45 mg/kg body weight, intraperitoneally, 3 times a wk for approximately 3 wk) significantly inhibited tumor growth (56.4% +/- 5.7 maximum reduction in tumor volumes) without toxicity. Analysis of tumors by immunohistochemistry and ELISA indicated that this effect is associated with increased apoptosis, reduced neovascularization, and inhibition of chemokine expression. Likewise mastic oil reduced vascular endothelial growth factor and chemokine release by Lewis lung carcinoma (LLC) cells. Furthermore, mastic oil administration decreased small guanosine triphosphatases (GTPases) Ras, RhoA and nuclear factor-kappa-B-dependent reporter gene expression in vivo and in vitro, indicating a mechanistic link between mastic oil activities and blocking of relevant signaling and transcription pathways. A dose-response comparison with perillyl alcohol and alpha-pinene, two of its components, revealed a higher efficacy of mastic oil, pointing to a beneficial collective interaction among its ingredients. Conclusively, our results provide novel in vivo evidence of mastic oil inhibitory effects on tumor growth and set a rational basis for its future application in cancer prevention.

  4. The preventive role of thoracic duct ligation on cerebral fat embolism in lung injury: an experimental study.

    PubMed

    Aydin, Mehmet Dumlu; Eroglu, Atilla; Gundogdu, Cemal; Turkyilmaz, Atila; Altas, Sare; Aydin, Nazan

    2008-11-01

    Cerebral fat embolism constitutes a major problem in intensive care units and treatment methods are highly controversial. Cerebral fat embolism has been thought to result from the migration of bone marrow fragments to the brain. However, the present authors observed that cerebral fat embolism is not possible unless the bone marrow particles cause alveolar wall destruction due to pulmonary artery occlusion. Thoracic duct ligation is essential for improved patient survival under such conditions. The aim was to investigate whether thoracic duct ligation plays a preventive role in cerebral fat embolism in lung injury. Pulmonary contusion was established with chest wall trauma in 20 male hybrid rabbits (n=20), with thoracic duct ligation being administered to half (n=10). Ten days after the procedure, all the rabbits were sacrificed. Brain specimens were taken using the frozen-section method, stained with Sudan Black, and examined microscopically. In the frozen brain sections the number of branches occluded by fat particles in both the central cerebral arteries was 15.5+/-3.02 in eight animals of the non-ligated group (GI) compared with 4.7+/-2.45 in two animals of the ligated group (GII). The number of occluded branches of the middle cerebral arteries was significantly higher in GI than in GII (p<0.001). The number of branches of both central cerebral arteries occluded by lipid particles was greater in the non-ligated than in the ligated animals. It is believed that thoracic duct ligation provides significant protection against fat embolism in cases of thoracic trauma.

  5. Exposure to hydrogen fluoride: an experimental study in humans of concentrations of fluoride in plasma, symptoms, and lung function.

    PubMed Central

    Lund, K; Ekstrand, J; Boe, J; Søstrand, P; Kongerud, J

    1997-01-01

    OBJECTIVES: To study the absorption of inhaled hydrogen fluoride (HF) by measuring plasma fluorides and HF concentrations in the breathing zone during exposure to HF. A possible dose-effect relation was investigated by following airway symptoms and lung function-that is, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)-during and after exposure to HF. METHODS: 20 healthy, male volunteers were exposed for one hour to constant HF concentrations that ranged from 0.2 to 5.2 mg/m3; these concentrations are known to occur among potroom workers in the primary aluminium industry. Plasma fluorides were analysed before, during, and after exposure. Symptoms from the eyes and the upper and lower airways were registered and graded from 1 to 5 with a standardised questionnaire. RESULTS: The total symptom score was significantly increased at the end of exposure for all the subjects as a group (P < 0.01) and for the group exposed to HF below the present Norwegian standard for total fluorides 0.6 mg/m3 (P = 0.05). No change was detected in FEV15 although a significant decrease was found in FVC in the group exposed to fluorides below the hygienic standard (n = 9) and for the entire group (n = 23). Almost all the symptoms had disappeared four hours after the end of exposure. Symptom scores from the upper airways were significantly correlated with the HF concentration (r = 0.62, P = 0.002), the change in plasma fluoride concentration (delta C) (r = 0.51, P = 0.01), and the maximum plasma fluoride concentration (Cmax) (r = 0.42, P = 0.05). A significant correlation was also found between the total symptom score for airways and the HF concentration. CONCLUSIONS: The present study showed a strong relation between inhaled HF and concentrations of fluoride in plasma. Upper airway and eye symptoms occurred after one hour of exposure to HF even when below the Norwegian hygienic standard for fluorides. PMID:9072031

  6. Lung Transplantation

    MedlinePlus

    ... who have severe COPD Cystic fibrosis Idiopathic pulmonary fibrosis Alpha-1 antitrypsin deficiency Pulmonary hypertension Complications of lung transplantation include rejection of the transplanted lung and infection. NIH: National Heart, Lung, and Blood Institute

  7. Lung disease

    MedlinePlus

    ... the lungs to take in oxygen and release carbon dioxide. People with this type of lung disorder often ... the lungs to take up oxygen and release carbon dioxide. These diseases may also affect heart function. An ...

  8. Collapsed Lung

    MedlinePlus

    A collapsed lung happens when air enters the pleural space, the area between the lung and the chest wall. If it is a ... is called pneumothorax. If only part of the lung is affected, it is called atelectasis. Causes of ...

  9. Time-resolved vibrational spectroscopy

    SciTech Connect

    Tokmakoff, Andrei; Champion, Paul; Heilweil, Edwin J.; Nelson, Keith A.; Ziegler, Larry

    2009-05-14

    This document contains the Proceedings from the 14th International Conference on Time-Resolved Vibrational Spectroscopy, which was held in Meredith, NH from May 9-14, 2009. The study of molecular dynamics in chemical reaction and biological processes using time-resolved spectroscopy plays an important role in our understanding of energy conversion, storage, and utilization problems. Fundamental studies of chemical reactivity, molecular rearrangements, and charge transport are broadly supported by the DOE's Office of Science because of their role in the development of alternative energy sources, the understanding of biological energy conversion processes, the efficient utilization of existing energy resources, and the mitigation of reactive intermediates in radiation chemistry. In addition, time-resolved spectroscopy is central to all fiveof DOE's grand challenges for fundamental energy science. The Time-Resolved Vibrational Spectroscopy conference is organized biennially to bring the leaders in this field from around the globe together with young scientists to discuss the most recent scientific and technological advances. The latest technology in ultrafast infrared, Raman, and terahertz spectroscopy and the scientific advances that these methods enable were covered. Particular emphasis was placed on new experimental methods used to probe molecular dynamics in liquids, solids, interfaces, nanostructured materials, and biomolecules.

  10. Resolving the Pericenter

    NASA Astrophysics Data System (ADS)

    Wisdom, Jack

    2015-10-01

    The Wisdom-Holman mapping method and its variations have become a mainstay of research in solar system dynamics. But the method is not without its limitations. Rauch & Holman noted that at large eccentricities sufficiently small steps must be taken to resolve the pericenter. In this paper, I explore in more detail what it means to resolve the pericenter.

  11. Comparison of the effects of low-dose vs. high-dose aminophylline on lung function in experimental meconium aspiration syndrome.

    PubMed

    Mokra, D; Drgova, A; Mokry, J; Pullmann, R; Redfors, B; Petraskova, M; Calkovska, A

    2008-12-01

    Due to missing information on appropriate dosing of aminophylline in meconium aspiration syndrome (MAS), this study compared effects of high-dose and low-dose aminophylline on lung function of animals with MAS. Meconium-instilled rabbits were treated by low-dose (LD, 1.0 mg/kg), or high-dose (HD, 2.0 mg/kg) aminophylline at 0.5 and 2.5 h after meconium instillation, or were left untreated. Within 5 h of oxygen ventilation, HD-aminophylline improved gas exchange, reduced pulmonary shunts and ventilatory pressures, and decreased edema formation and lung neutrophils. LD-aminophylline enhanced lung function to a lower extent than HD-aminophylline, and failed to reduce lung edema and the number of lung neutrophils. Both treatments decreased lung peroxidation, with a stronger effect of HD-aminophylline on lipid oxidation and of LD-aminophylline on protein oxidation. Tracheal reactivity to histamine decreased after HD-aminophylline, while lung tissue reactivity was more reduced after LD-aminophylline. Although LD-aminophylline showed some anti-inflammatory potential, HD-aminophylline improved most of the parameters more effectively.

  12. Advances in Stem Cell and Cell-Based Gene Therapy Approaches for Experimental Acute Lung Injury: A Review of Preclinical Studies.

    PubMed

    Mei, Shirley H J; Dos Santos, Claudia C; Stewart, Duncan J

    2016-10-01

    Given the failure of pharmacological interventions in acute respiratory distress syndrome (ARDS), researchers have been actively pursuing novel strategies to treat this devastating, life-threatening condition commonly seen in the intensive care unit. There has been considerable research on harnessing the reparative properties of stem and progenitor cells to develop more effective therapeutic approaches for respiratory diseases with limited treatment options, such as ARDS. This review discusses the preclinical literature on the use of stem and progenitor cell therapy and cell-based gene therapy for the treatment of preclinical animal models of acute lung injury (ALI). A variety of cell types that have been used in preclinical models of ALI, such as mesenchymal stem cells, endothelial progenitor cells, and induced pluripotent stem cells, were evaluated. At present, two phase I trials have been completed and one phase I/II clinical trial is well underway in order to translate the therapeutic benefit gleaned from preclinical studies in complex animal models of ALI to patients with ARDS, paving the way for what could potentially develop into transformative therapy for critically ill patients. As we await the results of these early cell therapy trials, future success of stem cell therapy for ARDS will depend on selection of the most appropriate cell type, route and timing of cell delivery, enhancing effectiveness of cells (i.e., potency), and potentially combining beneficial cells and genes (cell-based gene therapy) to maximize therapeutic efficacy. The experimental models and scientific methods exploited to date have provided researchers with invaluable knowledge that will be leveraged to engineer cells with enhanced therapeutic capabilities for use in the next generation of clinical trials.

  13. In vivo lung morphometry with hyperpolarized 3He diffusion MRI: Theoretical background

    NASA Astrophysics Data System (ADS)

    Sukstanskii, A. L.; Yablonskiy, D. A.

    2008-02-01

    MRI-based study of 3He gas diffusion in lungs may provide important information on lung microstructure. Lung acinar airways can be described in terms of cylinders covered with alveolar sleeve [Haefeli-Bleuer, Weibel, Anat. Rec. 220 (1988) 401]. For relatively short diffusion times (on the order of a few ms) this geometry allows description of the 3He diffusion attenuated MR signal in lungs in terms of two diffusion coefficients—longitudinal (D) and transverse (D) with respect to the individual acinar airway axis [Yablonskiy et al., PNAS 99 (2002) 3111]. In this paper, empirical relationships between D and D and the geometrical parameters of airways and alveoli are found by means of computer Monte Carlo simulations. The effects of non-Gaussian signal behavior (dependence of D and D on b-value) are also taken into account. The results obtained are quantitatively valid in the physiologically important range of airway parameters characteristic of healthy lungs and lungs with mild emphysema. In lungs with advanced emphysema, the results provide only "apparent" characteristics but still could potentially be used to evaluate emphysema progression. This creates a basis for in vivo lung morphometry—evaluation of the geometrical parameters of acinar airways from hyperpolarized 3He diffusion MRI, despite the airways being too small to be resolved by direct imaging. These results also predict a rather substantial dependence of 3He ADC on the experimentally-controllable diffusion time, Δ. If Δ is decreased from 3 ms to 1 ms, the ADC in normal human lungs may increase by almost 50%. This effect should be taken into account when comparing experimental data obtained with different pulse sequences.

  14. In vivo lung morphometry with hyperpolarized 3He diffusion MRI: theoretical background.

    PubMed

    Sukstanskii, A L; Yablonskiy, D A

    2008-02-01

    MRI-based study of (3)He gas diffusion in lungs may provide important information on lung microstructure. Lung acinar airways can be described in terms of cylinders covered with alveolar sleeve [Haefeli-Bleuer, Weibel, Anat. Rec. 220 (1988) 401]. For relatively short diffusion times (on the order of a few ms) this geometry allows description of the (3)He diffusion attenuated MR signal in lungs in terms of two diffusion coefficients-longitudinal (D(L)) and transverse (D(T)) with respect to the individual acinar airway axis [Yablonskiy et al., PNAS 99 (2002) 3111]. In this paper, empirical relationships between D(L) and D(T) and the geometrical parameters of airways and alveoli are found by means of computer Monte Carlo simulations. The effects of non-Gaussian signal behavior (dependence of D(L) and D(T) on b-value) are also taken into account. The results obtained are quantitatively valid in the physiologically important range of airway parameters characteristic of healthy lungs and lungs with mild emphysema. In lungs with advanced emphysema, the results provide only "apparent" characteristics but still could potentially be used to evaluate emphysema progression. This creates a basis for in vivo lung morphometry-evaluation of the geometrical parameters of acinar airways from hyperpolarized (3)He diffusion MRI, despite the airways being too small to be resolved by direct imaging. These results also predict a rather substantial dependence of (3)He ADC on the experimentally-controllable diffusion time, Delta. If Delta is decreased from 3 ms to 1 ms, the ADC in normal human lungs may increase by almost 50%. This effect should be taken into account when comparing experimental data obtained with different pulse sequences.

  15. Lung transplant

    MedlinePlus

    ... diseases that may require a lung transplant are: Cystic fibrosis Damage to the arteries of the lung because ... BC; Clinical Practice Guidelines for Pulmonary Therapies Committee; ... Therapies Committee. Cystic fibrosis pulmonary guidelines: ...

  16. Experimental bacterial pneumonia in rabbits: polymorphonuclear leukocyte margination and sequestration in rabbit lungs and quantitation and kinetics of /sup 51/Cr-labeled polymorphonuclear leukocytes in E. coli-induced lung lesions

    SciTech Connect

    Cybulsky, M.I.; Movat, H.Z.

    1982-12-01

    A relationship between the circulating and marginal polymorphonuclear leukocyte (PMN) pools was documented using /sup 51/Cr-labeled leukocytes as a marker. /sup 51/Cr-leukocytes marginating in the lungs were found to decrease following a first-order exponential decline, while /sup 51/Cr radioactivity accumulated in the liver and the spleen. Intravenously administered endotoxin caused a rapid selective disappearance of PMNs from the circulation. The percentage of infused /sup 51/Cr cells disappearing was equal to the percentage of disappearance of host cells. The PMNs were found to sequester in the lungs, with peak sequestration of labeled cells occurring 5 min after an endotoxin challenge. Over the next 25 min the /sup 51/Cr radioactivity in the lungs declined. Large numbers of PMNs, probably newly derived from the bone marrow, were observed histologically to be sequestered in the lung vasculature 90 min after an endotoxin dose, while the early sequestration of circulating leukocytes could not be assessed histologically. Pulmonary inflammatory lesions were induced selectively with Escherichia coli in the left lower lobes of rabbits, leaving the right lower lobes as intrinsic controls. PMN-accumulation into the lesions was quantitated using /sup 51/Cr-labeled blood leukocytes. With the aid of /sup 125/I-labeled E. coli, a logarithmic dose-response relationship was found between the number of E. coli and of PMNs. Over a 6-hr period circulating PMNs were found to accumulate in a lesion in the left lower lobe, whereas in the control right lower lobe, leukocyte radioactivity declined. These findings were confirmed with the aid of lavages of the right and left lungs. Two peaks of PMN-accumulation were found by studying leukocyte kinetics: a larger peak between 0 and 6 hr and a smaller peak 18-24 hr after instillation of the microorganisms. Histologic studies confirmed the accumulation of leukocytes, and by 3 weeks showed a complete resolution of the lesions.

  17. Conditionally replicating oncolytic adenoviral vector expressing arresten and tumor necrosis factor-related apoptosis-inducing ligand experimentally suppresses lung carcinoma progression.

    PubMed

    Li, Shudong; Qi, Zongli; Li, Huijin; Hu, Jun; Wang, Dongyang; Wang, Xin; Feng, Zhenzhen

    2015-08-01

    Current methods of treatment for lung carcinoma are ineffective for the majority of patients. Conditionally replicating adenoviruses (CRAds) represent a potential novel treatment for a number of neoplastic diseases, including lung carcinoma. The present study aimed to investigate the synergistic mechanisms underlying the anti-angiogenesis gene, arresten, and the apoptosis-inducing gene, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in order to evaluate their therapeutic potential in lung cancer. The two genes were expressed by CRAd, which was confirmed using reverse transcription-polymerase chain reaction and western blotting. In vitro analyses demonstrated that CRAd adenoviruses are capable of selectively inhibiting A549 lung cancer cell growth and replication but not in that of healthy cells. In vivo analyses demonstrated that the infection of A549 cell lines using CRAd armed with the two genes (CRAd-arresten-TRAIL) enhanced the tumor inhibition, compared with cells infected with CRAd-arresten, CRAd-TRAIL or CRAd, and with the control group. CRAd-arresten-TRAIL may therefore be useful in the treatment of lung cancer.

  18. Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia.

    PubMed

    Ray, Nancy B; Durairaj, Lakshmi; Chen, Bill B; McVerry, Bryan J; Ryan, Alan J; Donahoe, Michael; Waltenbaugh, Alisa K; O'Donnell, Christopher P; Henderson, Florita C; Etscheidt, Christopher A; McCoy, Diann M; Agassandian, Marianna; Hayes-Rowan, Emily C; Coon, Tiffany A; Butler, Phillip L; Gakhar, Lokesh; Mathur, Satya N; Sieren, Jessica C; Tyurina, Yulia Y; Kagan, Valerian E; McLennan, Geoffrey; Mallampalli, Rama K

    2010-10-01

    Pneumonia remains the leading cause of death from infection in the US, yet fundamentally new conceptual models underlying its pathogenesis have not emerged. We show that humans and mice with bacterial pneumonia have markedly elevated amounts of cardiolipin, a rare, mitochondrial-specific phospholipid, in lung fluid and find that it potently disrupts surfactant function. Intratracheal cardiolipin administration in mice recapitulates the clinical phenotype of pneumonia, including impaired lung mechanics, modulation of cell survival and cytokine networks and lung consolidation. We have identified and characterized the activity of a unique cardiolipin transporter, the P-type ATPase transmembrane lipid pump Atp8b1, a mutant version of which is associated with severe pneumonia in humans and mice. Atp8b1 bound and internalized cardiolipin from extracellular fluid via a basic residue-enriched motif. Administration of a peptide encompassing the cardiolipin binding motif or Atp8b1 gene transfer in mice lessened bacteria-induced lung injury and improved survival. The results unveil a new paradigm whereby Atp8b1 is a cardiolipin importer whose capacity to remove cardiolipin from lung fluid is exceeded during inflammation or when Atp8b1 is defective. This discovery opens the door for new therapeutic strategies directed at modulating the abundance or molecular interactions of cardiolipin in pneumonia.

  19. Lung Organogenesis

    PubMed Central

    Warburton, David; El-Hashash, Ahmed; Carraro, Gianni; Tiozzo, Caterina; Sala, Frederic; Rogers, Orquidea; De Langhe, Stijn; Kemp, Paul J.; Riccardi, Daniela; Torday, John; Bellusci, Saverio; Shi, Wei; Lubkin, Sharon R; Jesudason, Edwin

    2011-01-01

    Developmental lung biology is a field that has the potential for significant human impact: lung disease at the extremes of age continues to cause major morbidity and mortality worldwide. Understanding how the lung develops holds the promise that investigators can use this knowledge to aid lung repair and regeneration. In the decade since the “molecular embryology” of the lung was first comprehensively reviewed, new challenges have emerged—and it is on these that we focus the current review. Firstly, there is a critical need to understand the progenitor cell biology of the lung in order to exploit the potential of stem cells for the treatment of lung disease. Secondly, the current familiar descriptions of lung morphogenesis governed by growth and transcription factors need to be elaborated upon with the reinclusion and reconsideration of other factors, such as mechanics, in lung growth. Thirdly, efforts to parse the finer detail of lung bud signaling may need to be combined with broader consideration of overarching mechanisms that may be therapeutically easier to target: in this arena, we advance the proposal that looking at the lung in general (and branching in particular) in terms of clocks may yield unexpected benefits. PMID:20691848

  20. Knowledge Extraction from Atomically Resolved Images.

    PubMed

    Vlcek, Lukas; Maksov, Artem; Pan, Minghu; Vasudevan, Rama K; Kalinin, Sergei V

    2017-10-03

    Tremendous strides in experimental capabilities of scanning transmission electron microscopy and scanning tunneling microscopy (STM) over the past 30 years made atomically resolved imaging routine. However, consistent integration and use of atomically resolved data with generative models is unavailable, so information on local thermodynamics and other microscopic driving forces encoded in the observed atomic configurations remains hidden. Here, we present a framework based on statistical distance minimization to consistently utilize the information available from atomic configurations obtained from an atomically resolved image and extract meaningful physical interaction parameters. We illustrate the applicability of the framework on an STM image of a FeSexTe1-x superconductor, with the segregation of the chalcogen atoms investigated using a nonideal interacting solid solution model. This universal method makes full use of the microscopic degrees of freedom sampled in an atomically resolved image and can be extended via Bayesian inference toward unbiased model selection with uncertainty quantification.

  1. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices.

    PubMed

    Schilders, Kim A A; Eenjes, Evelien; van Riet, Sander; Poot, André A; Stamatialis, Dimitrios; Truckenmüller, Roman; Hiemstra, Pieter S; Rottier, Robbert J

    2016-04-23

    Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as understanding the biomechanical properties to build artificial lung devices. In addition, the continuing efforts to better define the disease origin, progression and pathology by basic scientists and clinicians contributes to insights in the basic principles of lung biology. However, the use of different model systems, experimental approaches and readout systems may generate somewhat conflicting or contradictory results. In an effort to summarize the latest developments in the lung epithelial stem cell biology, we provide an overview of the current status of the field. We first describe the different stem cells, or progenitor cells, residing in the homeostatic lung. Next, we focus on the plasticity of the different cell types upon several injury-induced activation or repair models, and highlight the regenerative capacity of lung cells. Lastly, we summarize the generation of lung mimics, such as air-liquid interface cultures, organoids and lung on a chip, that are required to test emerging hypotheses. Moreover, the increasing collaboration between distinct specializations will contribute to the eventual development of an artificial lung device capable of assisting reduced lung function and capacity in human patients.

  2. Comparison of different degrees of variability in tidal volume to prevent deterioration of respiratory system elastance in experimental acute lung inflammation.

    PubMed

    Kiss, T; Silva, P L; Huhle, R; Moraes, L; Santos, R S; Felix, N S; Santos, C L; Morales, M M; Capelozzi, V L; Kasper, M; Pelosi, P; Gama de Abreu, M; Rocco, P R M

    2016-05-01

    Variable ventilation improves respiratory function, but it is not known whether the amount of variability in tidal volume (VT) can be reduced in recruited lungs without a deterioration of respiratory system elastance. Acute lung inflammation was induced by intratracheal instillation of lipopolysaccharide in 35 Wistar rats. Twenty-eight animals were anaesthetized and ventilated in volume-controlled mode. Lungs were recruited by random variation of VT (mean 6 ml kg(-1), coefficient of variation 30%, normal distribution) for 30 min. Animals were randomly assigned to different amounts of VT variability (n=7 for 90 min per group): 30, 15, 7.5, or 0%. Lung function, diffuse alveolar damage, and gene expression of biological markers associated with cell mechanical stress, inflammation, and fibrogenesis were assessed. Seven animals were not ventilated and served as controls for post-mortem analyses. A VT variability of 30%, but not 15, 7.5, or 0%, prevented deterioration of respiratory system elastance [Mean (SD) -7.5 (8.7%), P<0.05; 21.1 (9.6%), P<0.05; 43.3 (25.9), P<0.05; and 41.2 (16.4), P<0.05, respectively]. Diffuse alveolar damage was lower with a VT variability of 30% than with 0% and without ventilation, because of reduced oedema and haemorrhage. A VT variability of 30, 15, or 7.5% reduced the gene expression of amphiregulin, cytokine-induced neutrophil chemoattractant-1, and tumour necrosis factor α compared with a VT variability of 0%. In this model of acute lung inflammation, a VT variability of 30%, compared with 15 and 7.5%, was necessary to avoid deterioration of respiratory system elastance and was not associated with lung histological damage. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Converging Stereotactic Radiotherapy Using Kilovoltage X-Rays: Experimental Irradiation of Normal Rabbit Lung and Dose-Volume Analysis With Monte Carlo Simulation

    SciTech Connect

    Kawase, Takatsugu; Kunieda, Etsuo Deloar, Hossain M.; Tsunoo, Takanori; Seki, Satoshi; Oku, Yohei; Saitoh, Hidetoshi; Saito, Kimiaki; Ogawa, Eileen N.; Ishizaka, Akitoshi; Kameyama, Kaori; Kubo, Atsushi

    2009-10-01

    Purpose: To validate the feasibility of developing a radiotherapy unit with kilovoltage X-rays through actual irradiation of live rabbit lungs, and to explore the practical issues anticipated in future clinical application to humans through Monte Carlo dose simulation. Methods and Materials: A converging stereotactic irradiation unit was developed, consisting of a modified diagnostic computed tomography (CT) scanner. A tiny cylindrical volume in 13 normal rabbit lungs was individually irradiated with single fractional absorbed doses of 15, 30, 45, and 60 Gy. Observational CT scanning of the whole lung was performed every 2 weeks for 30 weeks after irradiation. After 30 weeks, histopathologic specimens of the lungs were examined. Dose distribution was simulated using the Monte Carlo method, and dose-volume histograms were calculated according to the data. A trial estimation of the effect of respiratory movement on dose distribution was made. Results: A localized hypodense change and subsequent reticular opacity around the planning target volume (PTV) were observed in CT images of rabbit lungs. Dose-volume histograms of the PTVs and organs at risk showed a focused dose distribution to the target and sufficient dose lowering in the organs at risk. Our estimate of the dose distribution, taking respiratory movement into account, revealed dose reduction in the PTV. Conclusions: A converging stereotactic irradiation unit using kilovoltage X-rays was able to generate a focused radiobiologic reaction in rabbit lungs. Dose-volume histogram analysis and estimated sagittal dose distribution, considering respiratory movement, clarified the characteristics of the irradiation received from this type of unit.

  4. Technetium-fibrinogen lung scanning in canine lung contusion

    SciTech Connect

    Geller, E.; Khaw, B.A.; Strauss, H.W.; Carvalho, A.C.; Rajagopalan, B.; Jones, R.; Zapol, W.M.

    1984-07-01

    To detect experimentally induced acute lung contusion in anesthetized dogs, serial radionuclide images of the lung were recorded following intravenous infusion of 99mTc-labelled human fibrinogen (Tc-HF). The accumulation of Tc-HF in canine lungs was serially quantitated for up to 20 hours after lung contusion. A contusion (number1) was produced in one lung, Tc-HF was injected IV after 15 minutes, and 75 minutes later a contralateral lung contusion (number2) was produced in a series of 14 dogs. At autopsy the excised lungs were scanned, sectioned, and counted for radioactivity. Radiolabelled fibrinogen accumulated within 2-4 minutes of contusion number2 and remained stable over the next 20 hours in 14 dogs; contusion number1 was barely visible in four dogs. Lung Tc-HF activity in the central region of contusion number2 remained sixfold higher than in normal lung tissue. These data suggest that following lung contusion, fibrinogen deposition occurs rapidly and remains stable over a 20-hour interval of observation.

  5. Assessment of Peripheral Lung Mechanics

    PubMed Central

    Bates, Jason H.T.; Suki, Béla

    2008-01-01

    The mechanical properties of the lung periphery are major determinants of overall lung function, and can change dramatically in disease. In this review we examine the various experimental techniques that have provided data pertaining to the mechanical properties of the lung periphery, together with the mathematical models that have been used to interpret these data. These models seek to make a clear distinction between the central and peripheral compartments of the lung by encapsulating functional differences between the conducing airways, the terminal airways and the parenchyma. Such a distinction becomes problematic in disease, however, because of the inevitable onset of regional variations in mechanical behavior throughout the lung. Accordingly, lung models are used both in the inverse sense as vehicles for extracting physiological insight from experimental data, and in the forward sense as virtual laboratories for the testing of specific hypothesis about mechanisms such as the effects of regional heterogeneities. Pathologies such as asthma, acute lung injury and emphysema can alter the mechanical properties of the lung periphery through the direct alteration of intrinsic tissue mechanics, the development of regional heterogeneities in mechanical function, and the complete derecruitment of airspaces due to airway closure and alveolar collapse. We are now beginning to decipher the relative contributions of these various factors to pathological alterations in peripheral lung mechanics, which may eventually lead to the development and assessment of novel therapies. PMID:18463006

  6. Assessment of peripheral lung mechanics.

    PubMed

    Bates, Jason H T; Suki, Béla

    2008-11-30

    The mechanical properties of the lung periphery are major determinants of overall lung function, and can change dramatically in disease. In this review we examine the various experimental techniques that have provided data pertaining to the mechanical properties of the lung periphery, together with the mathematical models that have been used to interpret these data. These models seek to make a clear distinction between the central and peripheral compartments of the lung by encapsulating functional differences between the conducing airways, the terminal airways and the parenchyma. Such a distinction becomes problematic in disease, however, because of the inevitable onset of regional variations in mechanical behavior throughout the lung. Accordingly, lung models are used both in the inverse sense as vehicles for extracting physiological insight from experimental data, and in the forward sense as virtual laboratories for the testing of specific hypothesis about mechanisms such as the effects of regional heterogeneities. Pathologies such as asthma, acute lung injury and emphysema can alter the mechanical properties of the lung periphery through the direct alteration of intrinsic tissue mechanics, the development of regional heterogeneities in mechanical function, and the complete derecruitment of airspaces due to airway closure and alveolar collapse. We are now beginning to decipher the relative contributions of these various factors to pathological alterations in peripheral lung mechanics, which may eventually lead to the development and assessment of novel therapies.

  7. Fire-eater's lung.

    PubMed

    Załęska, Jolanta; Błaszczyk, Arkadiusz; Jakubowska, Lilia; Szopiński, Janusz; Polaczek, Mateusz; Grudny, Jacek; Zych, Jacek; Roszkowski-Śliż, Kazimierz

    2016-01-01

    Fire eater's lung (FEL) is an acute hydrocarbon pneumonitis caused by aspiration or inhalation into airways of liquid hydrocarbons. This disorder is classified into distinct form of chemical toxic pneumonitis. An amateur fire-eater is presented in this work. He accidentally aspirated into airways about 1/3 of glass of grill lighter fluid composed of mixture of liquid hydrocarbons. A few hours after this incident he had severe symptoms like weakness, high temperature, midsternal pleuritic chest pain, myalgia of the back, shortness of breath, and dry cough. Radiologic examination revealed consolidations with well-defined cavitary lesions (pneumatoceles) in lower lobes mainly in the left lower lobe. After one week of this event clinical improvement was observed. The lesions resolved nearly completly during three months. The review of the literature connected with fire-eater's lung is also presented.

  8. A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer.

    PubMed

    Shimaoka, Hideki; Takeno, Shinsuke; Maki, Kenji; Sasaki, Takahide; Hasegawa, Suguru; Yamashita, Yuichi

    2017-09-01

    Current therapy for rheumatoid arthritis (RA) relies on global suppression of the immune response or specific blockade of inflammatory cytokines. However, it is unclear how immunosuppressants affect patients with cancer. Therefore, in the present study, the effect of three biological agents, tofacitinib, anti-mouse IL-6 receptor antibody (MR16-1) and etanercept, which are used for the treatment of RA diseases, on a tumor-bearing mouse model was investigated. The effect of the three agents was examined using a mouse lung-metastasis model with the murine colon 26 cancer cell line. Lymphocyte subsets and natural killer (NK) cells in peripheral blood and spleen were analyzed using fluorescence-activated cell sorting, and the number of lung surface nodules was examined. In the continuous tofacitinib administration (15 mg/kg/day) group, the number of lung surface nodules was significantly increased compared with that of the vehicle-treated group (vehicle, 1.20±0.58; tofacitinib, 35.6±10.81; P<0.01). NK cell number in the blood and spleen of tofacitinib-treated mice was decreased 10-fold, and the percentage of cluster of differentiation (CD)11(+)CD27(-) NK cells was significantly reduced. MR16-1 [8 mg/mouse; once a week; intraperitoneal (i.p.)] or etanercept (1 mg/mouse; 3 times a week; i.p.) treatment did not affect the number of NK cells or lung metastasis. In the present study, immunosuppressants that target cytokines, including tofacitinib, were demonstrated to inhibit the proliferation and differentiation of NK cells, and exhibit the potential to promote cancer metastasis using a mouse model of lung metastasis.

  9. Evaluation of the preventive effect of dexpanthenol in radiation injury by lung perfusion scintigraphy: a preclinical experimental model of radiation injury.

    PubMed

    Koç, Zehra P; İn, Erdal; Karslioğlu, İhsan; Üçer, Özlem; Canpolat, Sinan

    2015-12-01

    The aim of this study was to show the preventative effects of dexpanthenol in radiation injuries caused by radiotherapy (RT) through the use of lung perfusion scintigraphy in the pre-RT and post-RT periods. Six male New Zealand rabbits (5-6 months of age and ∼2.5-3 kg in weight) were the used in this study. The animals were subjected to Tc-macroaggregated albumin lung perfusion scintigraphy in the pre-RT and post-RT (i.e. 2 weeks after treatment) periods. The scintigraphies were performed with the same dose by the same staff and the methodology used the same acquisition parameters. The rabbits were divided into two groups: group I (administered RT only) and group II (also administered intramuscular 500 mg dexpanthenol injections for 14 consecutive days after RT). Quantification was performed to compare the groups and the quantification variables were compared using a paired samples t-test, with P value less than 0.05 considered to be statistically significant. Histopathological analysis was also carried out. The post-RT scintigraphies indicated a decrease in the counts in both lungs, suggesting early post-RT injury. The difference between the counts obtained from both lungs in groups I and II was significantly different and favoured group II. Histopathological results confirmed the scintigraphy results. It is possible to estimate post-RT changes in the early period (in contrast to previous data) by lung perfusion scintigraphy. Dexpanthenol may also reduce the effects of RT to a degree. Although this is the first study to report the preventive effects of dexpanthenol on RT injuries, further studies are warranted in this area.

  10. Lung Epithelial Progenitor Cells

    PubMed Central

    Rawlins, Emma L.

    2008-01-01

    The current enthusiasm for stem cell research stems from the hope that damaged or diseased tissues may one day be repaired through the manipulation of endogenous or exogenous stem cells. The postnatal human respiratory system is highly accessible and provides unique opportunities for the application of such techniques. Several putative adult lung epithelial stem cells have been identified in the mouse model system. However, their in vivo capabilities to contribute to different lineages, and their control mechanisms, remain unclear. If stem cell–based therapies are to be successful in the lung, it is vitally important that we understand the normal behavior of adult lung stem cells, and how this is regulated. Lung embryonic progenitor cells are much better defined and characterized than their adult counterparts. Moreover, experiments on a variety of developing tissues are beginning to uncover general mechanisms by which embryonic progenitors influence final organ size and structure. This provides a framework for the study of lung embryonic progenitor cells, facilitating experimental design and interpretation. A similar approach to investigating adult lung stem cells could produce rapid advances in the field. PMID:18684716

  11. [The lung].

    PubMed

    Martinod, Emmanuel; Uzunhan, Yurdagül; Radu, Dana M; Seguin, Agathe; Boddaert, Guillaume; Valeyre, Dominique; Planès, Carole; Carpentier, Alain

    2011-10-01

    Lung transplantation is still the only curative treatment for end-stage pulmonary diseases. The results remain poor, however, because of the limited availability of lung donors, chronic rejection, and complications related to immunosuppressive therapy. The use of a bioartificial lung generated from autologous cells could offer a solution. We have demonstrated that in vivo epithelial and cartilage regeneration of the airways is feasible with the use of an aortic tissue matrix. Other studies show that in vitro and in vivo airway regeneration, respectively, can be obtained by using bio-engineering and heterotopic allograft implantation. A more complex challenge is the creation of an artificial lung Indeed, this would require the use of an elastic matrix that can promote regeneration of the different lung components (airways, alveoli, vessels) over a large surface area, thus allowing ventilation, blood perfusion and gas exchanges. Recent studies have demonstrated the possibility of in vitro and in vivo regeneration of lung tissue from autologous cells, and especially stem cells. This emerging research field is currently dominated by the use of decellularized lung matrices and autologous epithelial and endothelial cells. Implantation of such a recellularized matrix in animals has proved the feasibility of a functional bio-artificial lung. The first human transplantation of a bio-artificial lung should be possible within 10-20 years.

  12. The Therapeutic Potential of Differentiated Lung Cells from Embryonic Stem Cells in Lung Diseases.

    PubMed

    Mokhber Dezfouli, Mohammad Reza; Chaleshtori, Sirous Sadeghian; Dehghan, Mohammad Mehdi; Tavanaeimanesh, Hamid; Baharvand, Hossein; Tahamtani, Yaser

    2017-01-01

    Lung diseases cause great morbidity and mortality. The choice of effective medical treatment is limited and the number of lung diseases are difficult to treat with current treatments. The embryonic stem cells (ESCs) have the potential to differentiate into cell types of all three germinal layers, including lung epithelial cells. So they can be a potential source for new cell therapies for hereditary or acquired diseases of the airways and lungs. One method for treatment of lung diseases is cell therapy and the use of ESCs that can replace the damaged epithelial and endothelial cells. Progress using ESCs has developed slowly for lung regeneration because differentiation of lung cells from ESCs is more difficult as compared to differentiation of other cells. The review studies the therapeutic effects of differentiated lung cells from embryonic stem cells in lung diseases. There are few studies of differentiation of ESCs into a lineage of respiratory and then investigation of this cell in experimental model of lung diseases.

  13. Short-term effects of low-volume resuscitation with hypertonic saline and hydroxyethylstarch in an experimental model of lung contusion and haemorrhagic shock.

    PubMed

    Prunet, Bertrand; Cordier, Pierre-Yves; Prat, Nicolas; De Bourmont, Sophie; Couret, David; Lambert, Dominique; Michelet, Pierre

    2016-09-20

    This study aimed to assess the short-term respiratory tolerance and haemodynamic efficiency of low-volume resuscitation with hypertonic saline and hydroxyethylstarch (HS/HES) in a pig model of lung contusion and controlled haemorrhagic shock. We hypothesised that a low-volume of HS/HES after haemorrhagic shock did not impact contused lungs in terms of extravascular lung water 3hours after trauma. A lung contusion resulting from blunt chest trauma was induced in 28 anaesthetised female pigs with five bolt-shots to the right thoracic cage, followed by haemorrhagic shock and fluid resuscitation. Pigs were randomly allocated into two groups: fluid resuscitation by 4ml/kg of HS/HES, or fluid resuscitation by 10ml/kg of normal saline (NS). Monitoring was based on transpulmonary thermodilution and a pulmonary artery catheter. After 3h, animals were euthanized to measure extravascular lung water (EVLW) by gravimetry. Blunt chest trauma was followed by a transient collapse and hypoxaemia in both groups. Post-mortem gravimetric assessment demonstrated a significant difference between EVLW in the NS-group (8.1±0.7ml/kg) and in the HS/HES-group (6.2±0.6ml/kg, P=0.038). Based on a pathological EVLW threshold of > 7ml/kg, results indicated that only the NS-group experienced moderate pulmonary oedema, contrary to the HS/HES-group. After haemorrhagic shock, HS/HES infusion enabled the restoration of effective mean arterial pressure and cardiac index. Intrapulmonary shunting increased transiently after fluid resuscitation but there was no significant impairment of oxygenation. In this pig model of lung contusion, the short-term assessment of fluid resuscitation after haemorrhagic shock with 4ml/kg of HS/HES showed that pulmonary oedema was avoided compared to fluid resuscitation with 10ml/kg of NS. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  14. Effect of PEEP and Tidal Volume on Ventilation Distribution and End-Expiratory Lung Volume: A Prospective Experimental Animal and Pilot Clinical Study

    PubMed Central

    Becher, Tobias; Schädler, Dirk; Pulletz, Sven; Freitag-Wolf, Sandra; Weiler, Norbert; Frerichs, Inéz

    2013-01-01

    Introduction Lung-protective ventilation aims at using low tidal volumes (VT) at optimum positive end-expiratory pressures (PEEP). Optimum PEEP should recruit atelectatic lung regions and avoid tidal recruitment and end-inspiratory overinflation. We examined the effect of VT and PEEP on ventilation distribution, regional respiratory system compliance (CRS), and end-expiratory lung volume (EELV) in an animal model of acute lung injury (ALI) and patients with ARDS by using electrical impedance tomography (EIT) with the aim to assess tidal recruitment and overinflation. Methods EIT examinations were performed in 10 anaesthetized pigs with normal lungs ventilated at 5 and 10 ml/kg body weight VT and 5 cmH2O PEEP. After ALI induction, 10 ml/kg VT and 10 cmH2O PEEP were applied. Afterwards, PEEP was set according to the pressure-volume curve. Animals were randomized to either low or high VT ventilation changed after 30 minutes in a crossover design. Ventilation distribution, regional CRS and changes in EELV were analyzed. The same measures were determined in five ARDS patients examined during low and high VT ventilation (6 and 10 (8) ml/kg) at three PEEP levels. Results In healthy animals, high compared to low VT increased CRS and ventilation in dependent lung regions implying tidal recruitment. ALI reduced CRS and EELV in all regions without changing ventilation distribution. Pressure-volume curve-derived PEEP of 21±4 cmH2O (mean±SD) resulted in comparable increase in CRS in dependent and decrease in non-dependent regions at both VT. This implied that tidal recruitment was avoided but end-inspiratory overinflation was present irrespective of VT. In patients, regional CRS differences between low and high VT revealed high degree of tidal recruitment and low overinflation at 3±1 cmH2O PEEP. Tidal recruitment decreased at 10±1 cmH2O and was further reduced at 15±2 cmH2O PEEP. Conclusions Tidal recruitment and end-inspiratory overinflation can be assessed by EIT

  15. Paediatric lung recruitment: a review of the clinical evidence.

    PubMed

    Jauncey-Cooke, Jacqui; East, Chris E; Bogossian, Fiona

    2015-03-01

    Lung recruitment is used as an adjunct to lung protective ventilation strategies. Lung recruitment is a brief, deliberate elevation of transpulmonary pressures beyond what is achieved during tidal ventilation levels. The aim of lung recruitment is to maximise the number of alveoli participating in gas exchange particularly in distal and dependant regions of the lung. This may improve oxygenation and end expiratory levels. Restoration of end expiratory levels and stabilisation of the alveoli may reduce the incidence of ventilator induced lung injury (VILI). Various methods of lung recruitment have been studied in adult and experimental populations. This review aims to establish the evidence for lung recruitment in the pediatric population.

  16. Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung.

    PubMed

    Vidaña, Beatriz; Martínez, Jorge; Martínez-Orellana, Pamela; García Migura, Lourdes; Montoya, María; Martorell, Jaime; Majó, Natàlia

    2014-01-01

    The swine-origin pandemic (p) H1N1 influenza A virus causes mild upper-respiratory tract disease in most human patients. However, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. Recently, it has been suggested that different populations have different degrees of susceptibility to pH1N1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic characteristics. Here, we tested whether the pathologic patterns of influenza strains that produce different disease outcomes in humans could be reproduced in a ferret model. Our results revealed that the severities of infection did not correspond to particular viral isolate and were not associated with the clinical phenotypes of the corresponding patients. Severe pathological outcomes were associated with higher viral replication, especially in alveolar areas, and with an exacerbated innate cellular immune response that was characterised by substantial phagocytic and cytotoxic cell migration into the lungs. Moreover, detrimental innate cellular responses were linked to the up-regulation of several proinflammatory cytokines and chemokines and the down-regulation of IFNα in the lungs. Additionally, severe lung lesions were associated with greater up-regulations of pro-apoptotic markers and higher levels of apoptotic neutrophils and macrophages. In conclusion, this study confirmed that the clinicopathological outcomes of pH1N1 infection in ferrets were not only due to viral replication abilities but also depended on the hosts' capacities to mount efficient immune responses to control viral infection of the lung.

  17. Loss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12

    PubMed Central

    Tan, Jiangning; Tedrow, John R.; Nouraie, Mehdi; Dutta, Justin A.; Miller, David T.; Li, Xiaoyun; Yu, Shibing; Chu, Yanxia; Juan-Guardela, Brenda; Kaminski, Naftali; Ramani, Kritika; Biswas, Partha S.; Zhang, Yingze

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a disease characterized by the accumulation of apoptosis-resistant fibroblasts in the lung. We have previously shown that high expression of the transcription factor Twist1 may explain this prosurvival phenotype in vitro. However, this observation has never been tested in vivo. We found that loss of Twist1 in COL1A2+ cells led to increased fibrosis characterized by very significant accumulation of T cells and bone marrow–derived matrix-producing cells. We found that Twist1-null cells expressed high levels of the T cell chemoattractant CXCL12. In vitro, we found that the loss of Twist1 in IPF lung fibroblasts increased expression of CXCL12 downstream of increased expression of the noncanonical NF-κB transcription factor RelB. Finally, blockade of CXCL12 with AMD3100 attenuated the exaggerated fibrosis observed in Twist1-null mice. Transcriptomic analysis of 134 IPF patients revealed that low expression of Twist1 was characterized by enrichment of T cell pathways. In conclusion, loss of Twist1 in collagen-producing cells led to increased bleomycin-induced pulmonary fibrosis, which is mediated by increased expression of CXCL12. Twist1 expression is associated with dysregulation of T cells in IPF patients. Twist1 may shape the IPF phenotype and regulate inflammation in fibrotic lung injury. PMID:28179498

  18. Lung transplantation

    PubMed Central

    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

  19. Lung Diseases

    MedlinePlus

    When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lung disease have difficulty breathing. Millions of people in ...

  20. Lung Cancer

    MedlinePlus

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  1. Resolving writer's block.

    PubMed Central

    Huston, P.

    1998-01-01

    PROBLEM BEING ADDRESSED: Writer's block, or a distinctly uncomfortable inability to write, can interfere with professional productivity. OBJECTIVE OF PROGRAM: To identify writer's block and to outline suggestions for its early diagnosis, treatment, and prevention. MAIN COMPONENTS OF PROGRAM: Once the diagnosis has been established, a stepwise approach to care is recommended. Mild blockage can be resolved by evaluating and revising expectations, conducting a task analysis, and giving oneself positive feedback. Moderate blockage can be addressed by creative exercises, such as brainstorming and role-playing. Recalcitrant blockage can be resolved with therapy. Writer's block can be prevented by taking opportunities to write at the beginning of projects, working with a supportive group of people, and cultivating an ongoing interest in writing. CONCLUSIONS: Writer's block is a highly treatable condition. A systematic approach can help to alleviate anxiety, build confidence, and give people the information they need to work productively. PMID:9481467

  2. Operation Inherent Resolve

    DTIC Science & Technology

    2015-04-01

    model. OIR is a military mission included within a wider, complex, whole-of-government effort to counter ISIL and address the ongoing refugee crisis...DoS OIG made recom- mendations to improve the administration and monitoring of activi- ties with the Bureau of Population, Refugees and Migration (PRM...operations against ISIL in Iraq and Syria had been named Operation Inherent Resolve (OIR). OIR applied retroactively to all military airstrikes that had been

  3. What Is Lung Cancer?

    MedlinePlus

    ... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...

  4. Lung Cancer Screening

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease ...

  5. Lung Cancer Prevention

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Prevention (PDQ®)–Patient Version What is prevention? ... to keep cancer from starting. General Information About Lung Cancer Key Points Lung cancer is a disease ...

  6. Current status of lung transplantation.

    PubMed

    Lau, C L; Patterson, G A

    2003-11-01

    Two decades have passed since the first successful clinical lung transplant was performed in 1983, and, in the interim, lung transplantation has become the preferred treatment option for a variety of end-stage pulmonary diseases. Remarkable progress has been made in the field through refinement of technique and improved understanding of transplant immunology and microbiology. Unfortunately, donor shortages continue to limit the more widespread application of lung transplantation. In order to address this issue, marginal donors, living lobar and split lung donor techniques, and nonheartbeating donors have been used clinically to increase the number of donor lungs available. Chronic rejection of the lung allograft is currently the major hurdle limiting longterm survival. To date, prevention of known risk factors and treatment strategies have not lessened the devastating toll this process has on lung transplant survival. Better understanding of the cause of chronic rejection is needed in order to develop novel strategies for its treatment. Promotion of immune tolerance is a promising area that could potentially eliminate chronic rejection. The present article discusses recent advances in lung transplantation. It also details the major issues facing the field today. Only through continued clinical and experimental investigation will lung transplantation eventually reach its full potential.

  7. [An experimental study on targeting suicide gene therapy for lung cancer with HSV-TK driven by hTERT promoter].

    PubMed

    Wang, Yan-ping; Tang, Xiao-jun; Zhou, Qing-hua; Che, Guo-wei; Chen, Xiao-he; Zhu, Da-xing

    2008-09-01

    To study the approach of targeting expression of suicide gene HSV-TK driven by human telomerase catalytic subunit (hTERT) promoter in lung cancer cells, and to investigate inhibitory effect of HSV-TK/GCV driven by hTERT promoter on proliferation of lung cancer cell line A549 in vitro and in vivo. (1) Recombinant expression vectors of HSV-TK driven by hTERT promoter and SV40 promoter (pGL3-hTp-TK and pGL3-SV40-TK) were transfected into telomerase-positive human lung adenocarcinoma cell A549 and telomerase-negative human embryonic lung fibroblast cell MRC-5. The mRNA expression of TK gene was detected with RT-PCR method; (2) With the treatment of GCV, the proliferation of above transfected cells was investigated by MTT assay; Influence of GCV on apoptosis and cell cycle of these cells was evaluated with flow cytometry; (3) After the subcutaneously transplantation of A549 cells into nude mice, intra-tumor injection of plasmid-liposome as well as intra-peritoneal injection of GCV were performed to stUdy anti-tumor effects of pGL3-hTp-TK/GCV and pGL3-SV40-TK/GCV in vivo. (1) Enzyme digestion and PCR suggested that recombinant plasmids of pGL3-hTp-TK and pGL3-SV40-TK were successfully constructed; TK mRNA expression was detected in both A549 and MRC-5 cells transfected with pGL3-SV40-TK, also in A549 transfected with pGL3-hTp-TK, but not in MRC-5 transfected with pGL3-hTp-TK; (2) GCV showed significant inhibition effect on proliferation of A549 and MRC-5 transfected with pGL3-SV40-TK in vitro, also on that of A549 transfected with pGL3-hTp-TK, but not of MRC-5 transfected with pGL3-hTp-TK; With the treatment of GCV, apoptosis index (AI) of A549 cells transfected with pGL3-SV40-TK and pGL3-hTp-TK (21.58% and 23.19% respectively) increased significantly, compared with that of A549 transfected with pGL3-hTp and blank control; GCV enhanced the effects on AI in MRC-5 transfected with pGL3-SV40-TK (9.35%), but not with pGL3-hTp-TK (0.88%); (3) Inhibition ratio of pGL3-SV40-TK

  8. Resource Prospector: The RESOLVE Payload

    NASA Astrophysics Data System (ADS)

    Quinn, J.; Smith, J.; J., Captain; Paz, A.; Colaprete, A.; Elphic, R.; Zacny, K.

    2015-10-01

    NASA has been developing a lunar volatiles exploration payload named RESOLVE. Now the primary science payload on-board the Resource Prospector (RP) mission, RESOLVE, consists of several instruments that evaluate lunar volatiles.

  9. Resolve at CEBAF

    SciTech Connect

    Yunn, B C; Li, R; Simrock, S

    1995-01-01

    M. Lee's program RESOLVE has recently been in extensive use at CEBAF to help identify and correct optics problems in recirculation arcs and in linac beamlines encountered during the commissioning of the 4-GeV accelerator. The authors describe the integration of the program with their machine applications software package. A significant vertical focusing error in one of the recirculation arcs, which is attributed to edge focusing of dipole magnets, was found from the analysis of difference orbit measurement data. A corrective measure has been successfully implemented. Optics checks in the spreader and recombiner regions are discussed along with linac optics and 60Hz jitter. 7 refs., 4 figs.

  10. Resolve at CEBAF

    SciTech Connect

    Yunn, B. C.; Li, R.; Simrock, S.

    1995-12-31

    M. Lee`s program RESOLVE has recently been in extensive use at CEBAF to help identify and correct optics problems in recirculation arcs and in linac beamlines encountered during the commissioning of the 4- GeV accelerator. We describe the integration of the program with our machine applications software package. A significant vertical focusing error in one of the recirculation arcs, which is attributed to edge focusing of dipole magnets, was found from the analysis of difference orbit measurement data. A corrective measure has been successfully implemented. Optics checks in the spreader and recombiner regions are discussed along with linac optics and 60Hz jitter. 7 refs., 4 figs.

  11. Nanoparticle delivery in infant lungs

    PubMed Central

    Semmler-Behnke, Manuela; Kreyling, Wolfgang G.; Schulz, Holger; Takenaka, Shinji; Butler, James P.; Henry, Frank S.; Tsuda, Akira

    2012-01-01

    The lung surface is an ideal pathway to the bloodstream for nanoparticle-based drug delivery. Thus far, research has focused on the lungs of adults, and little is known about nanoparticle behavior in the immature lungs of infants. Here, using nonlinear dynamical systems analysis and in vivo experimentation in developing animals, we show that nanoparticle deposition in postnatally developing lungs peaks at the end of bulk alveolation. This finding suggests a unique paradigm, consistent with the emerging theory that as alveoli form through secondary septation, alveolar flow becomes chaotic and chaotic mixing kicks in, significantly enhancing particle deposition. This finding has significant implications for the application of nanoparticle-based inhalation therapeutics in young children with immature lungs from birth to ˜2 y of age. PMID:22411799

  12. Effect of naturally occurring monoterpenes carvone, limonene and perillic acid in the inhibition of experimental lung metastasis induced by B16F-10 melanoma cells.

    PubMed

    Raphael, T J; Kuttan, G

    2003-09-01

    The effects of naturally occurring monoterpenes on lung metastasis induced by B16F-10 melanoma cells were studied in C57BL/6 mice. Administration of monoterpenes such as limonene (100 micromoles/kg body wt. 10 doses i.p.) and perillic acid (50 micromoles/kg body wt 10 doses i.p.) remarkably reduced the metastatic tumour nodule formation by 65% and 67%, respectively. These results correlated with the biochemical parameters such as serum sialic acid, lung collagen hydroxyproline and uronic acid contents. Serum sialic acid level in control group was 126.8 microg/ml serum which was significantly lowered in limonene (49.3 microg/ml serum) and perillic acid treated animals (53.6 microg/ml serum). Uronic acid level was also inhibited to 56% and 39.7% in limonene and perillic acid treated animals, respectively. Histopathological studies also correlated with these above results. Administration of Carvone even at 100 micromoles/kg body wt. did not have any significant effect on the metastatic tumour growth. These results indicate that limonene and perillic acid could inhibit the metastatic progression of B16F-10 melanoma cells in mice.

  13. Dual Brushless Resolver Rate Sensor

    NASA Technical Reports Server (NTRS)

    Howard, David E. (Inventor)

    1997-01-01

    A resolver rate sensor is disclosed in which dual brushless resolvers are mechanically coupled to the same output shaft. Diverse inputs are provided to each resolver by providing the first resolver with a DC input and the second resolver with an AC sinusoidal input. A trigonometric identity in which the sum of the squares of the sin and cosine components equal one is used to advantage in providing a sensor of increased accuracy. The first resolver may have a fixed or variable DC input to permit dynamic adjustment of resolver sensitivity thus permitting a wide range of coverage. In one embodiment of the invention the outputs of the first resolver are directly inputted into two separate multipliers and the outputs of the second resolver are inputted into the two separate multipliers, after being demodulated in a pair of demodulator circuits. The multiplied signals are then added in an adder circuit to provide a directional sensitive output. In another embodiment the outputs from the first resolver is modulated in separate modulator circuits and the output from the modulator circuits are used to excite the second resolver. The outputs from the second resolver are demodulated in separate demodulator circuit and added in an adder circuit to provide a direction sensitive rate output.

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

    PubMed

    Lohser, Jens; Slinger, Peter

    2015-08-01

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

  15. Lung cancer

    MedlinePlus

    ... Sputum test to look for cancer cells Thoracentesis (sampling of fluid buildup around the lung) In most ... quitting, talk with your provider. There are many methods to help you quit, from support groups to ...

  16. Lung Transplant

    MedlinePlus

    ... will recover in the hospital’s intensive care unit (ICU) before moving to a hospital room for one to three weeks. Your doctor may recommend pulmonary rehabilitation after your lung transplant surgery to help you ...

  17. Spatially resolved and time-resolved imaging of transport of indirect excitons in high magnetic fields

    NASA Astrophysics Data System (ADS)

    Dorow, C. J.; Hasling, M. W.; Calman, E. V.; Butov, L. V.; Wilkes, J.; Campman, K. L.; Gossard, A. C.

    2017-06-01

    We present the direct measurements of magnetoexciton transport. Excitons give the opportunity to realize the high magnetic-field regime for composite bosons with magnetic fields of a few tesla. Long lifetimes of indirect excitons allow the study of kinetics of magnetoexciton transport with time-resolved optical imaging of exciton photoluminescence. We performed spatially, spectrally, and time-resolved optical imaging of transport of indirect excitons in high magnetic fields. We observed that an increasing magnetic field slows down magnetoexciton transport. The time-resolved measurements of the magnetoexciton transport distance allowed for an experimental estimation of the magnetoexciton diffusion coefficient. An enhancement of the exciton photoluminescence energy at the laser excitation spot was found to anticorrelate with the exciton transport distance. A theoretical model of indirect magnetoexciton transport is presented and is in agreement with the experimental data.

  18. Brief resolved unexplained event

    PubMed Central

    Arane, Karen; Claudius, Ilene; Goldman, Ran D.

    2017-01-01

    Abstract Question For many years, the term apparent life-threatening event (ALTE) was associated with sudden infant death syndrome, and parents who described an acute event in their infants were sent to the hospital for admission. I understand that for infants new terminology is recommended. What is the current approach to a near-death experience of an infant? Answer A recent clinical practice guideline revised the name and definition of an ALTE to a brief resolved unexplained event (BRUE). The diagnosis of BRUE in infants younger than 1 year of age is made when infants experience 1 of the following BRUE symptoms: a brief episode (ie, less than 1 minute and usually less than 20 to 30 seconds) that is entirely resolved (infant is at baseline), which remains unexplained after the history and physical examination are completed, and includes an event characterized by cyanosis or pallor; absent, decreased, or irregular breathing; hypertonia or hypotonia; or altered responsiveness. Low-risk infants should not be admitted to the hospital and overtesting is discouraged. PMID:28115439

  19. Cloud Resolving Modeling

    NASA Technical Reports Server (NTRS)

    Tao, Wei-Kuo

    2007-01-01

    One of the most promising methods to test the representation of cloud processes used in climate models is to use observations together with cloud-resolving models (CRMs). CRMs use more sophisticated and realistic representations of cloud microphysical processes, and they can reasonably well resolve the time evolution, structure, and life cycles of clouds and cloud systems (with sizes ranging from about 2-200 km). CRMs also allow for explicit interaction between clouds, outgoing longwave (cooling) and incoming solar (heating) radiation, and ocean and land surface processes. Observations are required to initialize CRMs and to validate their results. This paper provides a brief discussion and review of the main characteristics of CRMs as well as some of their major applications. These include the use of CRMs to improve our understanding of: (1) convective organization, (2) cloud temperature and water vapor budgets, and convective momentum transport, (3) diurnal variation of precipitation processes, (4) radiative-convective quasi-equilibrium states, (5) cloud-chemistry interaction, (6) aerosol-precipitation interaction, and (7) improving moist processes in large-scale models. In addition, current and future developments and applications of CRMs will be presented.

  20. RESOLVE 2010 Field Test

    NASA Technical Reports Server (NTRS)

    Captain, J.; Quinn, J.; Moss, T.; Weis, K.

    2010-01-01

    This slide presentation reviews the field tests conducted in 2010 of the Regolith Environment Science & Oxygen & Lunar Volatile Extraction (RESOLVE). The Resolve program consist of several mechanism: (1) Excavation and Bulk Regolith Characterization (EBRC) which is designed to act as a drill and crusher, (2) Regolith Volatiles Characterization (RVC) which is a reactor and does gas analysis,(3) Lunar Water Resources Demonstration (LWRD) which is a fluid system, water and hydrogen capture device and (4) the Rover. The scientific goal of this test is to demonstrate evolution of low levels of hydrogen and water as a function of temperature. The Engineering goals of this test are to demonstrate:(1) Integration onto new rover (2) Miniaturization of electronics rack (3) Operation from battery packs (elimination of generator) (4) Remote command/control and (5) Operation while roving. Views of the 2008 and the 2010 mechanisms, a overhead view of the mission path, a view of the terrain, the two drill sites, and a graphic of the Master Events Controller Graphical User Interface (MEC GUI) are shown. There are descriptions of the Gas chromatography (GC), the operational procedure, water and hydrogen doping of tephra. There is also a review of some of the results, and future direction for research and tests.

  1. Stacking-Dependent Electronic Structure of Trilayer Graphene Resolved by Nanospot Angle-Resolved Photoemission Spectroscopy.

    PubMed

    Bao, Changhua; Yao, Wei; Wang, Eryin; Chen, Chaoyu; Avila, José; Asensio, Maria C; Zhou, Shuyun

    2017-03-08

    The crystallographic stacking order in multilayer graphene plays an important role in determining its electronic structure. In trilayer graphene, rhombohedral stacking (ABC) is particularly intriguing, exhibiting a flat band with an electric-field tunable band gap. Such electronic structure is distinct from simple hexagonal stacking (AAA) or typical Bernal stacking (ABA) and is promising for nanoscale electronics and optoelectronics applications. So far clean experimental electronic spectra on the first two stackings are missing because the samples are usually too small in size (μm or nm scale) to be resolved by conventional angle-resolved photoemission spectroscopy (ARPES). Here, by using ARPES with a nanospot beam size (NanoARPES), we provide direct experimental evidence for the coexistence of three different stackings of trilayer graphene and reveal their distinctive electronic structures directly. By fitting the experimental data, we provide important experimental band parameters for describing the electronic structure of trilayer graphene with different stackings.

  2. Radionuclide injury to the lung.

    PubMed Central

    Dagle, G E; Sanders, C L

    1984-01-01

    Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequency observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed. PMID:6376095

  3. The diamond (111) surface: A dilemma resolved

    NASA Astrophysics Data System (ADS)

    Pate, B. B.; Waclawski, B. J.; Stefan, P. M.; Binns, C.; Ohta, T.; Hecht, M. H.; Jupiter, P. J.; Shek, M. L.; Pierce, D. T.; Swanson, N.; Celotta, R. J.; Lindau, I.; Spicer, W. E.; Rossi, G.

    1983-03-01

    A dilemma due to the experimental observation of a “clean” unreconstructed elemental semiconductor surface without band gap states is resolved. Results from photon stimulated ion desorption, high resolution low energy electron loss spectroscopy and photoemission spectroscopy find that the conventionally polished (in olive oil) diamond (111) 1 × 1 surface is atomically terminated and electronically stabilized by hydrogen. Thermal desorption of hydrogen upon heating (∼1000°C) results in a reconstructed 2 × {2}/{2} × 1 surface with filled electronic surface states in and near the fundamental gap. Exposure of the reconstructed surface to atomic hydrogen (or dueterium) is found to again terminate the surface and remove the near band gap surface states. Apparent inconsistencies (with respect to the experimental literature) in the understanding of the diamond:hydrogen interaction are resolved in terms of our work.

  4. Detection of a Molecular Biomarker for Zygomycetes by Quantitative PCR Assays of Plasma, Bronchoalveolar Lavage, and Lung Tissue in a Rabbit Model of Experimental Pulmonary Zygomycosis▿

    PubMed Central

    Kasai, Miki; Harrington, Susan M.; Francesconi, Andrea; Petraitis, Vidmantas; Petraitiene, Ruta; Beveridge, Mara G.; Knudsen, Tena; Milanovich, Jeffery; Cotton, Margaret P.; Hughes, Johanna; Schaufele, Robert L.; Sein, Tin; Bacher, John; Murray, Patrick R.; Kontoyiannis, Dimitrios P.; Walsh, Thomas J.

    2008-01-01

    We developed two real-time quantitative PCR (qPCR) assays, targeting the 28S rRNA gene, for the diagnosis of zygomycosis caused by the most common, clinically significant Zygomycetes. The amplicons of the first qPCR assay (qPCR-1) from Rhizopus, Mucor, and Rhizomucor species were distinguished through melt curve analysis. The second qPCR assay (qPCR-2) detected Cunninghamella species using a different primer/probe set. For both assays, the analytic sensitivity for the detection of hyphal elements from germinating sporangiospores in bronchoalveolar lavage (BAL) fluid and lung tissue homogenates from rabbits was 1 to 10 sporangiospores/ml. Four unique and clinically applicable models of invasive pulmonary zygomycosis served as surrogates of human infections, facilitating the validation of these assays for potential diagnostic utility. For qPCR-1, 5 of 98 infarcted lung specimens were positive by qPCR and negative by quantitative culture (qCx). None were qCx positive only. Among 23 BAL fluid samples, all were positive by qPCR, while 22 were positive by qCx. qPCR-1 detected Rhizopus and Mucor DNA in 20 (39%) of 51 serial plasma samples as early as day 1 postinoculation. Similar properties were observed for qPCR-2, which showed greater sensitivity than qCx for BAL fluid (100% versus 67%; P = 0.04; n = 15). The assay detected Cunninghamella DNA in 18 (58%) of 31 serial plasma samples as early as day 1 postinoculation. These qPCR assays are sensitive and specific for the detection of Rhizopus, Mucor, Rhizomucor, and Cunninghamella species and can be used for the study and detection of infections caused by these life-threatening pathogens. PMID:18845827

  5. Time-resolved optical spectroscopy of wood.

    PubMed

    D'Andrea, C; Farina, A; Comelli, D; Pifferi, A; Taroni, P; Valentini, G; Cubeddu, R; Zoia, L; Orlandi, M; Kienle, A

    2008-05-01

    We have proposed and experimentally demonstrated that picosecond time-resolved optical spectroscopy in the visible/near-infrared (NIR) region (700-1040 nm) is a useful technique for noninvasive characterization of wood. This technique has been demonstrated on both softwood and hardwood samples treated in different ways simulating the aging process suffered by waterlogged woods. In all the cases, alterations of absorption and scattering spectra were observed, revealing changes of chemical and structural composition.

  6. Time-resolved inverse Raman spectroscopy.

    PubMed

    Rahn, L A

    1982-02-01

    A technique for obtaining sensitive, highly reproducible, time-resolved inverse Raman measurements is reported. Experimental results are presented for the nitrogen vibrational Q branch at a pressure of 10 atm. For these measurements the signal, normalized to the pump-laser energy, exhibits fluctuations of 1.4% (rms) about the average of 500 measurements; these deviations are within a factor of 2 of the quantum noise limit.

  7. Spatially resolved multicomponent gels

    NASA Astrophysics Data System (ADS)

    Draper, Emily R.; Eden, Edward G. B.; McDonald, Tom O.; Adams, Dave J.

    2015-10-01

    Multicomponent supramolecular systems could be used to prepare exciting new functional materials, but it is often challenging to control the assembly across multiple length scales. Here we report a simple approach to forming patterned, spatially resolved multicomponent supramolecular hydrogels. A multicomponent gel is first formed from two low-molecular-weight gelators and consists of two types of fibre, each formed by only one gelator. One type of fibre in this ‘self-sorted network’ is then removed selectively by a light-triggered gel-to-sol transition. We show that the remaining network has the same mechanical properties as it would have done if it initially formed alone. The selective irradiation of sections of the gel through a mask leads to the formation of patterned multicomponent networks, in which either one or two networks can be present at a particular position with a high degree of spatial control.

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

    PubMed

    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.

  9. Immunohistochemical localization of transforming growth factor-beta 1 in rats with experimental silicosis, alveolar type II hyperplasia, and lung cancer.

    PubMed Central

    Williams, A. O.; Flanders, K. C.; Saffiotti, U.

    1993-01-01

    Immunohistochemical localization of transforming growth factor-beta 1 (TGF-beta 1) was studied in the lungs of rats given crystalline silica or ferric oxide by single intratracheal instillation. Ferric oxide elicited no progressive granulomatous reaction, no epithelial hyperplasia, and no lung tumors; no demonstrable reactivity to TGF-beta 1 was observed. Silica induced a granulomatous reaction with progressive fibrosis, adjacent alveolar type II hyperplasia, and alveolar carcinomas. Rabbit polyclonal antibodies to synthetic peptides corresponding to the first 30 amino acids of mature TGF-beta 1, anti-LC (1-30), and anti-CC (1-30) were used for the localization of intracellular and extracellular TGF-beta 1. An antibody to a peptide corresponding to amino acids 266-278 of the TGF-beta 1 precursor sequence, anti-Pre (266-278), was used to detect the TGF-beta precursor and the latency-associated peptide. Intracellular mature TGF-beta (anti-LC) was demonstrated in fibroblasts and macrophages located at the periphery of silicotic granulomas and in fibroblasts adjacent to hyperplastic type II cells. Extracellular mature TGF-beta 1 was localized in the connective tissue matrix of the granulomas and in the stroma of both hyperplastic type II cells and well-differentiated adenocarcinomas. Immunoreactivity to anti-Pre was localized, intracellularly, in hyperplastic alveolar type II cells and their proliferative lesions adjacent to granulomas, in adenomas, but not in adenocarcinomas. The hyperplastic type II cells appear to be the sites of production and secretion of TGF-beta 1, which may regulate their own growth and differentiation and mediate the production of extracellular TGF-beta 1-associated matrix. The lack of reactivity to TGF-beta 1 precursor in the adenocarcinomas is consistent with the loss of normal cellular differentiation and function. TGF-beta 1 appears to have a pathogenetic role in silica-induced mesenchymal and epithelial lesions. The role of TGF-beta 1 and

  10. Rheumatoid lung disease

    MedlinePlus

    Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The cause of lung disease associated with rheumatoid arthritis is unknown. Sometimes, the medicines used to ...

  11. Nutrition for Lung Cancer

    MedlinePlus

    ... by zip code or Select your state State Lung Cancer www.lung.org > Lung Health and Diseases > ... I Stay Healthy Share this page: Nutrition for Lung Cancer Key Points There is no prescribed diet ...

  12. Lung Nodules: Overview

    MedlinePlus

    ... Research & Science Education & Training Home Conditions Lung Nodules Lung Nodules Make an Appointment Find a Doctor Ask ... Kern, MD (June 01, 2016) What is a lung nodule? A lung nodule is also called a ...

  13. Eosinophilic Lung Disorders

    MedlinePlus

    ... Education & Training Home Conditions Eosinophilic Lung Disorders Eosinophilic Lung Disorders Make an Appointment Find a Doctor Ask ... Rafeul Alam, MD, PhD (July 01, 2012) Eosinophilic lung disorders are a category of lung problems characterized ...

  14. Lung Nodules: Overview

    MedlinePlus

    ... Research & Science Education & Training Home Conditions Lung Nodules Lung Nodules Make an Appointment Find a Doctor Ask ... Kern, MD (June 01, 2016) What is a lung nodule? A lung nodule is also called a ...

  15. Lung Cancer Screening

    MedlinePlus

    Lung cancer screening Overview By Mayo Clinic Staff Lung cancer screening is a process that's used to detect the presence ... with a high risk of lung cancer. Lung cancer screening is recommended for older adults who are longtime ...

  16. Lung cancer - small cell

    MedlinePlus

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  17. [Cryptogenic organizing non-resolving pneumonia. Report of one case].

    PubMed

    Olivares A, Felipe; Fica C, Alberto; Charpentier V, Paulo; Hernández M, Antonio; Manríquez A, María Eugenia; Castro S, Marcelo

    2014-02-01

    Non-resolving pneumonia is a common clinical problem that prolongs morbidity and increases hospitalization costs. We report an 82 year-old non-smoking female who was admitted with chronic diarrhea and later developed nosocomial pneumonia. Lung infiltrates did not resolve despite sequential antibiotic treatments. Infectious causes such as resistant nosocomial pathogens, respiratory viruses, tuberculosis, Legionellosis, cytomegalovirus or agents associated with HIV infection were discarded. Non-infectious causes such as thromboembolic lung disease, neoplasms and rheumatic disorders were also ruled out. An exudative pleural effusion was detected, but the study was unremarkable. Fiberoptic bronchoscopy and a transbronchial biopsy, revealed nonspecific findings. The patient persisted febrile, required non-invasive mechanical ventilation and displayed a migratory pattern of lung infiltrates that motivated a second biopsy, this time by open thoracotomy, showing a cryptogenic organizing pneumonia. The patient's conditions improved after treatment with adrenal steroids. In patients with non-resolving pneumonia, a dedicated and comprehensive study should be done using invasive procedures and considering both infectious and non-infectious causes. Cryptogenic organizing pneumonia is one of the alternatives that is potentially treatable, but often underdiagnosed.

  18. Tsunami lung.

    PubMed

    Inoue, Yoshihiro; Fujino, Yasuhisa; Onodera, Makoto; Kikuchi, Satoshi; Shozushima, Tatsuyori; Ogino, Nobuyoshi; Mori, Kiyoshi; Oikawa, Hirotaka; Koeda, Yorihiko; Ueda, Hironobu; Takahashi, Tomohiro; Terui, Katsutoshi; Nakadate, Toshihide; Aoki, Hidehiko; Endo, Shigeatsu

    2012-04-01

    We encountered three cases of lung disorders caused by drowning in the recent large tsunami that struck following the Great East Japan Earthquake. All three were females, and two of them were old elderly. All segments of both lungs were involved in all the three patients, necessitating ICU admission and endotracheal intubation and mechanical ventilation. All three died within 3 weeks. In at least two cases, misswallowing of oil was suspected from the features noted at the time of the detection. Sputum culture for bacteria yielded isolation of Stenotrophomonas maltophilia, Legionella pneumophila, Burkholderia cepacia, and Pseudomonas aeruginosa. The cause of tsunami lung may be a combination of chemical induced pneumonia and bacterial pneumonia.

  19. Stereology of the lung.

    PubMed

    Schneider, Jan Philipp; Ochs, Matthias

    2013-01-01

    Many scientific projects require a quantitative assessment of organ, tissue and cell (ultra)structure. Such quantitative (morphometric) data are essential to make statistically valid comparisons between experimental groups. The structures of interest are measured at different microscopic levels. However, measurements in microscopy pose two problems: 1) Only a small fraction of the whole biological system can be analyzed (sampling problem). 2) The analysis is performed on nearly two-dimensional (physical, optical or virtual) sections through the object although the aim is to obtain biologically meaningful three-dimensional data (3D vs 2D problem). These problems are solved by the application of unbiased sampling and measurement tools known as stereology. This chapter gives a brief introduction to the theory and practical application of stereology, using the lung as an example. Stereological tools needed to quantify volume, number and surface area are introduced and examples are given how to estimate total lung volume, volume of lung parenchyma, alveolar surface area and number of alveolar epithelial type II cells per lung.

  20. Lung imaging.

    PubMed

    Ley, Sebastian

    2015-06-01

    Imaging of the lung is a mainstay of respiratory medicine. It provides local information about morphology and function of the lung parenchyma that is unchallenged by other noninvasive techniques. During the 2014 European Respiratory Society International Congress in Munich, Germany, a Clinical Year in Review session was held focusing on the latest developments in pulmonary imaging. This review summarises some of the main findings of peer-reviewed articles that were published in the 12-month period prior to the 2014 International Congress. Copyright ©ERS 2015.

  1. Angle-resolved optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Desjardins, Adrien Emmanuel

    Optical coherence tomography (OCT) has emerged as a powerful tool for probing the microstructure of biological tissue non-invasively at high-speed. OCT measures depth-resolved reflectance of infrared light, generating cross-sectional images non-invasively with micron-scale resolution. As with other imaging modalities that employ coherent detection, OCT images are confounded by speckle noise. Speckle imposes a grainy texture on images that reduces the signal-to-noise ratio to near unity values. As a result, it conceals subtle differences in scattering properties known to be crucial for differentiating normal from diseased tissue states. In this thesis, we developed a novel OCT modality called "Angle-Resolved OCT" in which depth scans (A-lines) are obtained simultaneously from a broad range of backscattering angles. We demonstrated that high levels of speckle reduction can be achieved by averaging the magnitudes of A-lines corresponding to the same transverse locations. With both experimental and analytic approaches, we demonstrated that this averaging method does not lead to a substantial loss in spatial resolution. We developed two different imaging systems for performing Angle-Resolved OCT. With the first system, angular data was acquired simultaneously; with the second, it was acquired sequentially. The first system had superior speckle-reduction capabilities but image quality degraded significantly with small sample movements. The second system allowed for in vivo imaging, as demonstrated with Resolved OCT systems, the speckle-reduced images showed hitherto unprecedented delineation of tissue microstructure.

  2. Dual Brushless Resolver Rate Sensor

    NASA Technical Reports Server (NTRS)

    Howard, David E. (Inventor)

    1996-01-01

    This invention relates to dual analog angular rate sensors which are implemented without the use of mechanical brushes. A resolver rate sensor which includes two brushless resolvers which are mechanically coupled to the same output shaft is provided with inputs which are provided to each resolver by providing the first resolver with a DC input and the second resolver with an AC sinusoidal input. A trigonometric identity in which the sum of the squares of the sin and cosine components equal one is used to advantage in providing a sensor of increased accuracy. The first resolver may have a fixed or variable DC input to permit dynamic adjustment of resolver sensitivity thus permitting a wide range of coverage. Novelty and advantages of the invention reside in the excitation of a resolver with a DC signal and in the utilization of two resolvers and the trigonometric identity of cos(exp 2)(theta) + sin(exp 2)(theta) = 1 to provide an accurate rate sensor which is sensitive to direction and accurate through zero rate.

  3. [Humidifier lung].

    PubMed

    Gerber, P; de Haller, R; Pyrozynski, W J; Sturzenegger, E R; Brändli, O

    1981-02-07

    Breathing air from a humidifier or an air conditioning unit contaminated by various microorganisms can cause an acute lung disease involving fever, cough and dyspnea, termed "humidifier fever". This type of hypersensitivity pneumonitis was first described in 1959 by PESTALOZZI in the Swiss literature and subsequently by BANASZAK et al. in the Anglo-American. Here a chronic form of this disease which led to pulmonary fibrosis is described: A 37-year-old woman who works in a cheese shop presented with dyspnea which had been progressive over two years, weight loss, a diffuse reticular pattern radiographically and a severe restrictive defect in lung function tests. Open lung biopsy revealed chronic interstitial and alveolar inflammation with non-caseating granulomas and fibrotic changes. Circulating immune complexes and precipitins against the contaminated humidifier water and cheese mites were found, but no antibodies suggesting legionnaires' disease. Two out of five otherwise healthy employees of this cheese shop, where a new humidifying system had been installed 7 years earlier, also had precipitins against the contaminated water from the humidifier and the cheese mites. Despite ending of exposure and longterm steroid and immunosuppressive therapy, the signs and symptoms of pulmonary fibrosis persisted. Contrary to the acute disease, this chronic form is termed "humidifier lung". The importance is stressed of investigating the possibility of exposure to contaminated humidifiers or air conditioning units in all cases of newly detected pulmonary fibrosis.

  4. Pharmacokinetic correlation between experimental and clinical effects on human non-small cell lung cancers of cis-diammineglycolatoplatinum (254-S) and cis-diamminedichloroplatinum.

    PubMed

    Koenuma, M; Kasai, H; Uchida, N; Wada, T; Hattori, M; Oguma, T; Totani, T; Inaba, M

    1995-01-01

    We attempted to correlate the in vitro and in vivo antitumor activities of cis-diammineglycolatoplatinum (254-S), a novel platinum complex, and cis-diamminedichloro-platinum (CDDP) against the established culture cell lines and xenografts of human non-small cell lung cancer (NSCLC) with their clinical effects, based on the previous finding that the cytotoxicity of CDDP depends on the area under the curve (AUC). The concentration of 254-S and CDDP inhibiting the in vitro growth of 4 cultured NSCLC lines by 50% (IC50) was 0.82-7.8 and 0.53-4.2 micrograms/ml, respectively, showing a similar level. Of the 4 cell lines, only the most sensitive line, RERF-LC-AI, showed an IC50 close to a specific concentration (0.50 for 254-S and 0.32 micrograms/ml for CDDP) that reproduces in vitro the clinical AUCfree (24.8 and 5.34 micrograms-hr/ml) of the respective drugs. We treated 6 lines of human NSCLC xenografts implanted in nude mice with 254-S and CDDP at a particular dose (13.2 and 3.7 mg/kg) that is equivalent to the clinical doses with respect to the plasma AUCfree. 254-S and CDDP exhibited significant antitumor effects on 2 and 1 of the 6 lines, respectively. These in vitro and in vivo findings were considered to be relatively well correlated with the reported clinical response rates of 15-19% for 254-S and 14-15% for CDDP.

  5. What Are Lung Carcinoid Tumors?

    MedlinePlus

    ... Carcinoid Tumor About Lung Carcinoid Tumors What Are Lung Carcinoid Tumors? Lung carcinoid tumors (also known as ... lungs, as well as the neuroendocrine system. The lungs The lungs are 2 sponge-like organs in ...

  6. What Is the Best Method to Fit Time-Resolved Data? A Comparison of the Residual Minimization and the Maximum Likelihood Techniques As Applied to Experimental Time-Correlated, Single-Photon Counting Data.

    PubMed

    Santra, Kalyan; Zhan, Jinchun; Song, Xueyu; Smith, Emily A; Vaswani, Namrata; Petrich, Jacob W

    2016-03-10

    The need for measuring fluorescence lifetimes of species in subdiffraction-limited volumes in, for example, stimulated emission depletion (STED) microscopy, entails the dual challenge of probing a small number of fluorophores and fitting the concomitant sparse data set to the appropriate excited-state decay function. This need has stimulated a further investigation into the relative merits of two fitting techniques commonly referred to as "residual minimization" (RM) and "maximum likelihood" (ML). Fluorescence decays of the well-characterized standard, rose bengal in methanol at room temperature (530 ± 10 ps), were acquired in a set of five experiments in which the total number of "photon counts" was approximately 20, 200, 1000, 3000, and 6000 and there were about 2-200 counts at the maxima of the respective decays. Each set of experiments was repeated 50 times to generate the appropriate statistics. Each of the 250 data sets was analyzed by ML and two different RM methods (differing in the weighting of residuals) using in-house routines and compared with a frequently used commercial RM routine. Convolution with a real instrument response function was always included in the fitting. While RM using Pearson's weighting of residuals can recover the correct mean result with a total number of counts of 1000 or more, ML distinguishes itself by yielding, in all cases, the same mean lifetime within 2% of the accepted value. For 200 total counts and greater, ML always provides a standard deviation of <10% of the mean lifetime, and even at 20 total counts there is only 20% error in the mean lifetime. The robustness of ML advocates its use for sparse data sets such as those acquired in some subdiffraction-limited microscopies, such as STED, and, more importantly, provides greater motivation for exploiting the time-resolved capacities of this technique to acquire and analyze fluorescence lifetime data.

  7. What is the best method to fit time-resolved data? A comparison of the residual minimization and the maximum likelihood techniques as applied to experimental time-correlated, single-photon counting data

    SciTech Connect

    Santra, Kalyan; Zhan, Jinchun; Song, Xueyu; Smith, Emily A.; Vaswani, Namrata; Petrich, Jacob W.

    2016-02-10

    The need for measuring fluorescence lifetimes of species in subdiffraction-limited volumes in, for example, stimulated emission depletion (STED) microscopy, entails the dual challenge of probing a small number of fluorophores and fitting the concomitant sparse data set to the appropriate excited-state decay function. This need has stimulated a further investigation into the relative merits of two fitting techniques commonly referred to as “residual minimization” (RM) and “maximum likelihood” (ML). Fluorescence decays of the well-characterized standard, rose bengal in methanol at room temperature (530 ± 10 ps), were acquired in a set of five experiments in which the total number of “photon counts” was approximately 20, 200, 1000, 3000, and 6000 and there were about 2–200 counts at the maxima of the respective decays. Each set of experiments was repeated 50 times to generate the appropriate statistics. Each of the 250 data sets was analyzed by ML and two different RM methods (differing in the weighting of residuals) using in-house routines and compared with a frequently used commercial RM routine. Convolution with a real instrument response function was always included in the fitting. While RM using Pearson’s weighting of residuals can recover the correct mean result with a total number of counts of 1000 or more, ML distinguishes itself by yielding, in all cases, the same mean lifetime within 2% of the accepted value. For 200 total counts and greater, ML always provides a standard deviation of <10% of the mean lifetime, and even at 20 total counts there is only 20% error in the mean lifetime. Here, the robustness of ML advocates its use for sparse data sets such as those acquired in some subdiffraction-limited microscopies, such as STED, and, more importantly, provides greater motivation for exploiting the time-resolved capacities of this technique to acquire and analyze fluorescence lifetime data.

  8. What is the best method to fit time-resolved data? A comparison of the residual minimization and the maximum likelihood techniques as applied to experimental time-correlated, single-photon counting data

    DOE PAGES

    Santra, Kalyan; Zhan, Jinchun; Song, Xueyu; ...

    2016-02-10

    The need for measuring fluorescence lifetimes of species in subdiffraction-limited volumes in, for example, stimulated emission depletion (STED) microscopy, entails the dual challenge of probing a small number of fluorophores and fitting the concomitant sparse data set to the appropriate excited-state decay function. This need has stimulated a further investigation into the relative merits of two fitting techniques commonly referred to as “residual minimization” (RM) and “maximum likelihood” (ML). Fluorescence decays of the well-characterized standard, rose bengal in methanol at room temperature (530 ± 10 ps), were acquired in a set of five experiments in which the total number ofmore » “photon counts” was approximately 20, 200, 1000, 3000, and 6000 and there were about 2–200 counts at the maxima of the respective decays. Each set of experiments was repeated 50 times to generate the appropriate statistics. Each of the 250 data sets was analyzed by ML and two different RM methods (differing in the weighting of residuals) using in-house routines and compared with a frequently used commercial RM routine. Convolution with a real instrument response function was always included in the fitting. While RM using Pearson’s weighting of residuals can recover the correct mean result with a total number of counts of 1000 or more, ML distinguishes itself by yielding, in all cases, the same mean lifetime within 2% of the accepted value. For 200 total counts and greater, ML always provides a standard deviation of <10% of the mean lifetime, and even at 20 total counts there is only 20% error in the mean lifetime. Here, the robustness of ML advocates its use for sparse data sets such as those acquired in some subdiffraction-limited microscopies, such as STED, and, more importantly, provides greater motivation for exploiting the time-resolved capacities of this technique to acquire and analyze fluorescence lifetime data.« less

  9. Time-resolved photoemission using attosecond streaking

    NASA Astrophysics Data System (ADS)

    Nagele, S.; Pazourek, R.; Wais, M.; Wachter, G.; Burgdörfer, J.

    2014-04-01

    We theoretically study time-resolved photoemission in atoms as probed by attosecond streaking. We review recent advances in the study of the photoelectric efect in the time domain and show that the experimentally accessible time shifts can be decomposed into distinct contributions that stem from the feld-free photoionization process itself and from probe-field induced corrections. We perform accurate quantum-mechanical as well as classical simulations of attosecond streaking for efective one-electron systems and determine all relevant contributions to the time delay with attosecond precision. In particular, we investigate the properties and limitations of attosecond streaking for the transition from short-ranged potentials (photodetachment) to long-ranged Coulomb potentials (photoionization). As an example for a more complex system, we study time-resolved photoionization for endohedral fullerenes A@C60 and discuss how streaking time shifts are modifed due to the interaction of the C60 cage with the probing infrared streaking field.

  10. Lung cancer stem cells—characteristics, phenotype

    PubMed Central

    George, Rachel; Sethi, Tariq

    2016-01-01

    Lung cancer remains a major cause of cancer-related deaths worldwide with unfavourable prognosis mainly due to the late stage of disease at presentation. High incidence and disease recurrence rates are a fact despite advances in treatment. Ongoing experimental and clinical observations suggest that the malignant phenotype in lung cancer is sustained by lung cancer stem cells (CSCs) which are putative stem cells situated throughout the airways that have the potential of initiating lung cancer formation. These cells share the common characteristic of increased proliferation and differentiation, long life span and resistance to chemotherapy and radiation therapy. This review summarises the current knowledge on their characteristics and phenotype. PMID:27413709

  11. Comparison of the protoscolocidal effectiveness of hypertonic saline, povidone-iodine and albendazole solutions in an experimental lung hydatid cyst model.

    PubMed

    Durgun Yetim, T; Basoglu, A; Taslak Sengul, A; Yetim, I; Serdar Bekdemir, O; Hokelek, M

    2011-01-01

    Secondary hydatidosis is an important problem encountered during the surgical treatment of hydatid cysts. This study describes an experimental model of secondary hydatidosis by cyst inoculation, used to explore whether simultaneous inoculation of protoscolocidal agents could prevent secondary hydatidosis. Fertile cyst fluid was injected into the pleural space of rabbits alone (group 1, n = 8), and in combination with 2% albendazole solution (group 2, n = 8), 20% hypertonic saline (group 3, n = 8) or 10% povidone-iodine (group 4, n = 8). Computed tomography imaging of the thorax, indirect haemagglutination (IHA) titres and eosinophil counts were used to determine cyst development. After 16 months, three control rabbits had pneumothorax, seven had cysts and four had parenchymal nodules. Histopathological investigation of nodules revealed 87.5% cyst formation. Pleural thickening was observed in rabbits from all groups. Cyst formation rates, IHA titres and eosinophilia counts were higher in group 1 than in groups 2-4. This study demonstrated the experimental formation of secondary hydatidosis and found that topical protoscolocidal agents were beneficial in preventing cyst recurrence.

  12. Can the preterm lung recover from perinatal stress?

    PubMed

    Hütten, Matthias C; Wolfs, Tim G A M; Kramer, Boris W

    2016-12-01

    After birth, adequate lung function is necessary for the successful adaptation of a preterm baby. Both prenatal and postnatal insults and therapeutic interventions have an immediate effect on lung function and gas exchange but also interfere with fetal and neonatal lung development. Prenatal insults like chorioamnionitis and prenatal interventions like maternal glucocorticosteroids interact but might also determine the preterm baby's lung response to postnatal interventions ("second hit") like supplementation of oxygen and drug therapy. We review current experimental and clinical findings on the influence of different perinatal factors on preterm lung development and discuss how well-established interventions in neonatal care might be adapted to attenuate postnatal lung injury.

  13. Resolution of Acute Inflammation In The Lung

    PubMed Central

    Levy, Bruce D.; Serhan, Charles N.

    2015-01-01

    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 pro-resolving 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

  14. Automated Lung Segmentation from HRCT Scans with Diffuse Parenchymal Lung Diseases.

    PubMed

    Pulagam, Ammi Reddy; Kande, Giri Babu; Ede, Venkata Krishna Rao; Inampudi, Ramesh Babu

    2016-08-01

    Performing accurate and fully automated lung segmentation of high-resolution computed tomography (HRCT) images affected by dense abnormalities is a challenging problem. This paper presents a novel algorithm for automated segmentation of lungs based on modified convex hull algorithm and mathematical morphology techniques. Sixty randomly selected lung HRCT scans with different abnormalities are used to test the proposed algorithm, and experimental results show that the proposed approach can accurately segment the lungs even in the presence of disease patterns, with some limitations in the apices and bases of lungs. The algorithm demonstrates a high segmentation accuracy (dice similarity coefficient = 98.62 and shape differentiation metrics dmean = 1.39 mm, and drms = 2.76 mm). Therefore, the developed automated lung segmentation algorithm is a good candidate for the first stage of a computer-aided diagnosis system for diffuse lung diseases.

  15. Cellular senescence in normal and premature lung aging.

    PubMed

    Bartling, B

    2013-10-01

    The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.

  16. Lung Oxidative Damage by Hypoxia

    PubMed Central

    Araneda, O. F.; Tuesta, M.

    2012-01-01

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

  17. Lung oxidative damage by hypoxia.

    PubMed

    Araneda, O F; Tuesta, M

    2012-01-01

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

  18. Importance of mast cell Prss31/transmembrane tryptase/tryptase-γ in lung function and experimental chronic obstructive pulmonary disease and colitis.

    PubMed

    Hansbro, Philip M; Hamilton, Matthew J; Fricker, Michael; Gellatly, Shaan L; Jarnicki, Andrew G; Zheng, Dominick; Frei, Sandra M; Wong, G William; Hamadi, Sahar; Zhou, Saijun; Foster, Paul S; Krilis, Steven A; Stevens, Richard L

    2014-06-27

    Protease serine member S31 (Prss31)/transmembrane tryptase/tryptase-γ is a mast cell (MC)-restricted protease of unknown function that is retained on the outer leaflet of the plasma membrane when MCs are activated. We determined the nucleotide sequences of the Prss31 gene in different mouse strains and then used a Cre/loxP homologous recombination approach to create a novel Prss31(-/-) C57BL/6 mouse line. The resulting animals exhibited no obvious developmental abnormality, contained normal numbers of granulated MCs in their tissues, and did not compensate for their loss of the membrane tryptase by increasing their expression of other granule proteases. When Prss31-null MCs were activated with a calcium ionophore or by their high affinity IgE receptors, they degranulated in a pattern similar to that of WT MCs. Prss31-null mice had increased baseline airway reactivity to methacholine but markedly reduced experimental chronic obstructive pulmonary disease and colitis, thereby indicating both beneficial and adverse functional roles for the tryptase. In a cigarette smoke-induced model of chronic obstructive pulmonary disease, WT mice had more pulmonary macrophages, higher histopathology scores, and more fibrosis in their small airways than similarly treated Prss31-null mice. In a dextran sodium sulfate-induced acute colitis model, WT mice lost more weight, had higher histopathology scores, and contained more Cxcl-2 and IL-6 mRNA in their colons than similarly treated Prss31-null mice. The accumulated data raise the possibility that inhibitors of this membrane tryptase may provide additional therapeutic benefit in the treatment of humans with these MC-dependent inflammatory diseases.

  19. Reflux and Lung Disease

    MedlinePlus

    ... Healthy Eating Reflux and Lung Disease Reflux and Lung Disease Make an Appointment Ask a Question Find a Doctor Many people with chronic lung disease also suffer from gastroesophageal reflux (GERD). In this ...

  20. Interstitial Lung Disease

    MedlinePlus

    ... Conditions Interstitial Lung Disease (ILD)/Pulmonary Fibrosis Interstitial Lung Disease (ILD)/Pulmonary Fibrosis Make an Appointment Refer ... ILD clinical trials and most effective therapies. Interstitial Lung Disease Care at National Jewish Health At National ...

  1. Lung transplantation from donation after cardiac death (non-heart-beating) donors.

    PubMed

    Oto, Takahiro

    2008-11-01

    Although lung transplantation is a well-accepted treatment for advanced lung diseases, donor shortage remains a significant limiting factor resulting in an increasing number of deaths of people on waiting lists. Recently, some transplant centers have begun to use lungs retrieved from donors after circulatory arrest. This review outlines the relevant published experimental data and clinical experiences with lung transplantation from donation after cardiac-death donors (DCDs) or non-heart-beating donors (NHBDs). Techniques for lung preservation and ex vivo lung assessment of DCD (NHBD) lungs are reviewed, and aspects of primary graft dysfunction after DCD (NHBD) lung transplantation are discussed.

  2. Experimental evaluations of the accuracy of 3D and 4D planning in robotic tracking stereotactic body radiotherapy for lung cancers.

    PubMed

    Chan, Mark K H; Kwong, Dora L W; Ng, Sherry C Y; Tong, Anthony S M; Tam, Eric K W

    2013-04-01

    Due to the complexity of 4D target tracking radiotherapy, the accuracy of this treatment strategy should be experimentally validated against established standard 3D technique. This work compared the accuracy of 3D and 4D dose calculations in respiration tracking stereotactic body radiotherapy (SBRT). Using the 4D planning module of the CyberKnife treatment planning system, treatment plans for a moving target and a static off-target cord structure were created on different four-dimensional computed tomography (4D-CT) datasets of a thorax phantom moving in different ranges. The 4D planning system used B-splines deformable image registrations (DIR) to accumulate dose distributions calculated on different breathing geometries, each corresponding to a static 3D-CT image of the 4D-CT dataset, onto a reference image to compose a 4D dose distribution. For each motion, 4D optimization was performed to generate a 4D treatment plan of the moving target. For comparison with standard 3D planning, each 4D plan was copied to the reference end-exhale images and a standard 3D dose calculation was followed. Treatment plans of the off-target structure were first obtained by standard 3D optimization on the end-exhale images. Subsequently, they were applied to recalculate the 4D dose distributions using DIRs. All dose distributions that were initially obtained using the ray-tracing algorithm with equivalent path-length heterogeneity correction (3D EPL and 4D EPL) were recalculated by a Monte Carlo algorithm (3D MC and 4D MC) to further investigate the effects of dose calculation algorithms. The calculated 3D EPL, 3D MC, 4D EPL, and 4D MC dose distributions were compared to measurements by Gafchromic EBT2 films in the axial and coronal planes of the moving target object, and the coronal plane for the static off-target object based on the γ metric at 5%/3mm criteria (γ5%/3mm). Treatment plans were considered acceptable if the percentage of pixels passing γ5%/3mm (Pγ<1) ≥ 90%. The

  3. Two-color ghost imaging with enhanced angular resolving power

    SciTech Connect

    Karmakar, Sanjit; Shih, Yanhua

    2010-03-15

    This article reports an experimental demonstration on nondegenerate, two-color, biphoton ghost imaging which reproduced a ghost image with enhanced angular resolving power by means of a greater field of view compared with that of classical imaging. With the same imaging magnification, the enhanced angular resolving power and field of view compared with those of classical imaging are 1.25:1 and 1.16:1, respectively. The enhancement of angular resolving power depends on the ratio between the idler and the signal photon frequencies, and the enhancement of the field of view depends mainly on the same ratio and also on the distances of the object plane and the imaging lens from the two-photon source. This article also reports the possibility of reproducing a ghost image with the enhancement of the angular resolving power by means of a greater imaging amplification compared with that of classical imaging.

  4. Experimental evaluations of the accuracy of 3D and 4D planning in robotic tracking stereotactic body radiotherapy for lung cancers

    SciTech Connect

    Chan, Mark K. H.; Kwong, Dora L. W.; Ng, Sherry C. Y.; Tong, Anthony S. M.; Tam, Eric K. W.

    2013-04-15

    Purpose: Due to the complexity of 4D target tracking radiotherapy, the accuracy of this treatment strategy should be experimentally validated against established standard 3D technique. This work compared the accuracy of 3D and 4D dose calculations in respiration tracking stereotactic body radiotherapy (SBRT). Methods: Using the 4D planning module of the CyberKnife treatment planning system, treatment plans for a moving target and a static off-target cord structure were created on different four-dimensional computed tomography (4D-CT) datasets of a thorax phantom moving in different ranges. The 4D planning system used B-splines deformable image registrations (DIR) to accumulate dose distributions calculated on different breathing geometries, each corresponding to a static 3D-CT image of the 4D-CT dataset, onto a reference image to compose a 4D dose distribution. For each motion, 4D optimization was performed to generate a 4D treatment plan of the moving target. For comparison with standard 3D planning, each 4D plan was copied to the reference end-exhale images and a standard 3D dose calculation was followed. Treatment plans of the off-target structure were first obtained by standard 3D optimization on the end-exhale images. Subsequently, they were applied to recalculate the 4D dose distributions using DIRs. All dose distributions that were initially obtained using the ray-tracing algorithm with equivalent path-length heterogeneity correction (3D{sub EPL} and 4D{sub EPL}) were recalculated by a Monte Carlo algorithm (3D{sub MC} and 4D{sub MC}) to further investigate the effects of dose calculation algorithms. The calculated 3D{sub EPL}, 3D{sub MC}, 4D{sub EPL}, and 4D{sub MC} dose distributions were compared to measurements by Gafchromic EBT2 films in the axial and coronal planes of the moving target object, and the coronal plane for the static off-target object based on the {gamma} metric at 5%/3mm criteria ({gamma}{sub 5%/3mm}). Treatment plans were considered

  5. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... are available to help. HELPFUL WEB SITES ON LUNG CANCER American Lung Association www.lung.org Lungcancer.org www.lungcancer.org Lung Cancer Alliance www.lungcanceralliance.org Lung Cancer Online www. ...

  6. Risks of Lung Cancer Screening

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease ...

  7. PEEP decreases atelectasis and extravascular lung water but not lung tissue volume in surfactant-washout lung injury.

    PubMed

    Luecke, Thomas; Roth, Harry; Herrmann, Peter; Joachim, Alf; Weisser, Gerald; Pelosi, Paolo; Quintel, Michael

    2003-11-01

    To examine the effects of positive end-expiratory pressure (PEEP) on extravascular lung water (EVLW), lung tissue, and lung volume. Experimental animal study at a university research facility. Fifteen adult sheep. All animals were studied before and after saline washout-induced lung injury while ventilated with sequentially increasing PEEP (0, 7, 14, or 21 cmH(2)O). Lung volume was determined by computed tomography and EVLW by the thermal dye dilution technique. Saline washout significantly increased lung tissue volume (21+/-3 to 37+/-5 ml/kg) and EVLW (9+/-2 to 36+/-9 ml/kg). While increasing levels of PEEP reduced EVLW (30+/-7, 24+/-8, and 18+/-4 ml/kg), lung tissue volume remained constant. Total lung volume significantly increased (50+/-8 ml/kg at PEEP 0 to 77+/-12 ml/kg at PEEP 21). Nonaerated lung volume significantly decreased and was closely correlated with the changes in EVLW ( r=0.67). In addition, a highly significant correlation was found between PEEP-induced decrease in nonaerated lung volume and decrease in transpulmonary shunt ( r=0.83). The main findings are as follows: (a) PEEP effectively decreases EVLW. (b) The decrease in EVLW is closely correlated with the PEEP-induced decrease in nonaerated lung volume, making EVLW a valuable bedside parameter indicating alveolar recruitment, similar to measurements of transpulmonary shunt. (c) As excess tissue volume remained constant, however, EVLW may not be suitable to reflect overall severity of lung disease

  8. [Lung transplantation. State of the art].

    PubMed

    García-Covarrubias, Lisardo; Salerno, Tomas A; Panos, Anthony L; Pham, Si M

    2007-01-01

    Lung transplantation is currently considered an established treatment for some advanced lung diseases. The beginning of experimental lung transplantation dates back to the 1940's when the Soviet Vladimir P. Demikhov performed the first lung transplants in animals. Two decades later, James Hardy performed the first lung transplant in humans. Unfortunately, the beginning of clinical lung transplantation was hampered by technical complications and the excessive toxicity of immunosuppressive drugs. Improvement in the surgical technique along with the development of more effective and less toxic immunosuppressive drugs has led to a better outcome in lunt transplant recipients. Donor selection and management before organ procurement play a key role in the receptor's outcome. Due to the shortage of donors, some institutions are using more liberal selection criteria, reporting satisfactory outcomes. The approach of the lung and heart-lung transplant patient is multidisciplinary and includes the cardiothoracic transplant surgeon, pulmonologist, anesthesiologist, and intensivist, among others. Herein, we review some relevant historical aspects and recent advances in the management of lung transplant recipients, including indications and contraindications, evaluation of donors and recipients, surgical techniques and peripost-operative care.

  9. Lung Macrophage Diversity and Asthma

    PubMed Central

    2016-01-01

    Macrophages (MPs) are one of the most prominent leukocyte populations in the lung and, in many ways, a forgotten player in asthma pathogenesis. Diverse functions in asthma initiation and maintenance in chronic disease have been demonstrated, which has led to confusion as to if pulmonary MPs are agents of good or evil in asthma. Much of this is due to the wide diversity of MP populations in the lung, many of which are inaccessible experimentally in most clinical studies. This review frames lung MP biology in the context of location, phenotype, function, and response phase in asthma pathogenesis. It also assesses new findings regarding MP diversity that have challenged old dogmas and generates new ways to understand how MPs function. PMID:27027949

  10. Vitamin C as an antioxidant: evaluation of its role on pulmonary contusion experimental model.

    PubMed

    Sirmali, Rana; Giniş, Zeynep; Sirmali, Mehmet; Solak, Okan; Şeliman, Bengü; Ağaçkiran, Yetkin; Delibaş, Namık

    2014-01-01

    To analyze the protective activity of vitamin C on the lungs by assessing biochemical and histopathological analysi after performing an experimental isolated lung contusion model. Fifty-four male Sprague-Dawley male rats were used. The rats were randomly separated into 4 groups Vitamin C (200 mg/kg) was injected intraperitoneally 30 min after trauma. Blood samples were obtained for myeloperoxidase (MPO) glutirthione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities and malondialdehyde (MDA) levels Blood gas analysis and bronchoalveolar lavage was performed. The lung tissue was also extracted for histopathological examination. The lung contusion enhanced MDA, SOD, CAT, and MPO and diminished GSH-Px. Vitamin C administration after th pulmonary contusion was found to diminish the level of MDA and the activities of SOD, CAT, and MPO and to enhance the level of GSH-Px (P < 0.05). Contusion-induced disrupted gas analysis and leukocyte infiltration were both resolved by the vitamin C. The present results indicate that vitamin C administration attenuated the oxidative damage and morphological change induced by pulmonary contusion in an experimental rat study.

  11. Resolving boosted jets with XCone

    NASA Astrophysics Data System (ADS)

    Thaler, Jesse; Wilkason, Thomas F.

    2015-12-01

    We show how the recently proposed XCone jet algorithm [1] smoothly interpolates between resolved and boosted kinematics. When using standard jet algorithms to reconstruct the decays of hadronic resonances like top quarks and Higgs bosons, one typically needs separate analysis strategies to handle the resolved regime of well-separated jets and the boosted regime of fat jets with substructure. XCone, by contrast, is an exclusive cone jet algorithm that always returns a fixed number of jets, so jet regions remain resolved even when (sub)jets are overlapping in the boosted regime. In this paper, we perform three LHC case studies — dijet resonances, Higgs decays to bottom quarks, and all-hadronic top pairs — that demonstrate the physics applications of XCone over a wide kinematic range.

  12. Lung surfactant.

    PubMed Central

    Rooney, S A

    1984-01-01

    Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, beta-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed. PMID:6145585

  13. Mechanisms of ventilator-induced lung injury in healthy lungs.

    PubMed

    Silva, Pedro Leme; Negrini, Daniela; Rocco, Patricia Rieken Macêdo

    2015-09-01

    Mechanical ventilation is an essential method of patient support, but it may induce lung damage, leading to ventilator-induced lung injury (VILI). VILI is the result of a complex interplay among various mechanical forces that act on lung structures, such as type I and II epithelial cells, endothelial cells, macrophages, peripheral airways, and the extracellular matrix (ECM), during mechanical ventilation. This article discusses ongoing research focusing on mechanisms of VILI in previously healthy lungs, such as in the perioperative period, and the development of new ventilator strategies for surgical patients. Several experimental and clinical studies have been conducted to evaluate the mechanisms of mechanotransduction in each cell type and in the ECM, as well as the role of different ventilator parameters in inducing or preventing VILI. VILI may be attenuated by reducing the tidal volume; however, the use of higher or lower levels of positive end-expiratory pressure (PEEP) and recruitment maneuvers during the perioperative period is a matter of debate. Many questions concerning the mechanisms of VILI in surgical patients remain unanswered. The optimal threshold value of each ventilator parameter to reduce VILI is also unclear. Further experimental and clinical studies are necessary to better evaluate ventilator settings during the perioperative period in different types of surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Targeted delivery of magnetic aerosol droplets to the lung.

    PubMed

    Dames, Petra; Gleich, Bernhard; Flemmer, Andreas; Hajek, Kerstin; Seidl, Nicole; Wiekhorst, Frank; Eberbeck, Dietmar; Bittmann, Iris; Bergemann, Christian; Weyh, Thomas; Trahms, Lutz; Rosenecker, Joseph; Rudolph, Carsten

    2007-08-01

    The inhalation of medical aerosols is widely used for the treatment of lung disorders such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, respiratory infection and, more recently, lung cancer. Targeted aerosol delivery to the affected lung tissue may improve therapeutic efficiency and minimize unwanted side effects. Despite enormous progress in optimizing aerosol delivery to the lung, targeted aerosol delivery to specific lung regions other than the airways or the lung periphery has not been adequately achieved to date. Here, we show theoretically by computer-aided simulation, and for the first time experimentally in mice, that targeted aerosol delivery to the lung can be achieved with aerosol droplets comprising superparamagnetic iron oxide nanoparticles--so-called nanomagnetosols--in combination with a target-directed magnetic gradient field. We suggest that nanomagnetosols may be useful for treating localized lung disease, by targeting foci of bacterial infection or tumour nodules.

  15. Ventilator-induced Lung Injury

    PubMed Central

    Kneyber, Martin C. J.; Zhang, Haibo; Slutsky, Arthur S.

    2016-01-01

    It is well established that mechanical ventilation can injure the lung, producing an entity known as ventilator-induced lung injury (VILI). There are various forms of VILI, including volutrauma (i.e., injury caused by overdistending the lung), atelectrauma (injury due to repeated opening/closing of lung units), and biotrauma (release of mediators that can induce lung injury or aggravate pre-existing injury, potentially leading to multiple organ failure). Experimental data in the pediatric context are in accord with the importance of VILI, and appear to show age-related susceptibility to VILI, although a conclusive link between use of large Vts and mortality has not been demonstrated in this population. The relevance of VILI in the pediatric intensive care unit population is thus unclear. Given the physiological and biological differences in the respiratory systems of infants, children, and adults, it is difficult to directly extrapolate clinical practice from adults to children. This Critical Care Perspective analyzes the relevance of VILI to the pediatric population, and addresses why pediatric patients might be less susceptible than adults to VILI. PMID:25003705

  16. Interstitial Lung Diseases

    MedlinePlus

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to ... air is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among ...

  17. Children's Use of Gesture to Resolve Lexical Ambiguity

    ERIC Educational Resources Information Center

    Kidd, Evan; Holler, Judith

    2009-01-01

    We report on a study investigating 3-5-year-old children's use of gesture to resolve lexical ambiguity. Children were told three short stories that contained two homonym senses; for example, "bat" (flying mammal) and "bat" (sports equipment). They were then asked to re-tell these stories to a second experimenter. The data were coded for the means…

  18. Children's Use of Gesture to Resolve Lexical Ambiguity

    ERIC Educational Resources Information Center

    Kidd, Evan; Holler, Judith

    2009-01-01

    We report on a study investigating 3-5-year-old children's use of gesture to resolve lexical ambiguity. Children were told three short stories that contained two homonym senses; for example, "bat" (flying mammal) and "bat" (sports equipment). They were then asked to re-tell these stories to a second experimenter. The data were coded for the means…

  19. Resolving Ethical Issues at School

    ERIC Educational Resources Information Center

    Benninga, Jacques S.

    2013-01-01

    Although ethical dilemmas are a constant in teachers' lives, the profession has offered little in the way of training to help teachers address such issues. This paper presents a framework, based on developmental theory, for resolving professional ethical dilemmas. The Four-Component Model of Moral Maturity, when used in conjunction with a…

  20. Resolving Ethical Issues at School

    ERIC Educational Resources Information Center

    Benninga, Jacques S.

    2013-01-01

    Although ethical dilemmas are a constant in teachers' lives, the profession has offered little in the way of training to help teachers address such issues. This paper presents a framework, based on developmental theory, for resolving professional ethical dilemmas. The Four-Component Model of Moral Maturity, when used in conjunction with a…

  1. Virginia Resolves, 1993-1994.

    ERIC Educational Resources Information Center

    Morrow, S. Rex, Ed.

    1994-01-01

    These two issues of "Virginia Resolves" provide articles of interest to the social studies reader and provides ideas for social studies instruction and curriculum. The fall issue features seven articles: (1) "Death and the Young Child" (Rosanne J. Marek); (2) "Simulations: Bibliography for the Middle and Elementary…

  2. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

  3. Lung cancer screening and management.

    PubMed

    Jones, G S; Baldwin, D R

    2015-12-01

    Deaths from lung cancer are greater than for any other type of malignancy. Many people present with advanced stage cancer at diagnosis and survival is limited. Low radiation dose CT (LDCT) screening appears to offer part of the solution to this. The US National Lung Screening Trial (NLST) showed a 20% reduction in cancer related mortality and a 6.7% reduction in all cause mortality in patients who had LDCT compared to chest X-ray. Lung Cancer screening is now being implemented in the US using the NLST screening criteria but many questions remain about the details of the methodology of screening and its cost effectiveness. Many of these questions are being answered by ongoing European trials that are reporting their findings. In this review we objectively analyse current research evidence and explore the issues that need to be resolved before implementation, including technical considerations, selection criteria and effective nodule management protocols. We discuss the potential barriers that will be faced when beginning a national screening programme and possible solutions to them.

  4. Peri-emphysematous lung infection.

    PubMed

    Mahler, D A; D'Esopo, N D

    1981-01-01

    The difficulty in classifying pulmonary infection within areas of bullous emphysema may have contributed to the lack of appreciation of this entity. This process is important to recognize because: (1) the clinical picture is usually benign:; (2) it may be confused with tuberculosis, fungal disease, and carcinoma of the lung; and (3) radiographic resolution may be slow. For these reasons, pneumonitis which occurs within emphysematous lung may have been previously considered as slowly resolving pneumonias. The development of air-fluid levels within bullae has been called "infected emphysematous bullae." We believe that this phrase is misleading since there are no bacteriologic data to support the presence of infection within the bullae containing fluid. In fact, direct sampling of intrabullous fluid has been rarely reported and, if obtained, has been generally negative for bacteria. Furthermore, the clinical course in our patients is alos not consistent with infection within a space. Once fiberoptic bronchoscopy has excluded an obstructing endobronchial lesion, the physician may patiently follow the anticipated gradual resolution. We suggest that the phrase, "periemphysematous lung infection" best describes these related clinical-radiological conditions.

  5. Successful use of bronchoscopic lung insufflation to treat left lung atelectasis.

    PubMed

    Abu-Hasan, Mutasim N; Chesrown, Sarah E; Jantz, Michael A

    2013-03-01

    We report first use of bronchoscopic lung insufflation in a child to treat acute left lung collapse. The patient is a 6-year old male asthmatic who was hospitalized with a 2-day history of cough, chest pain, and abdominal pain. He was tachypneic and hypoxemic on room air. Chest exam revealed diminished breath sounds on the left side. Chest X-ray and Chest CT showed complete left lung collapse. He underwent bronchoscopic lung insufflation procedure by injecting total of 200 ml air via flexible bronchoscope in the left upper lobe using 50cc syringe aliquots followed by similar injection of 200 ml of air in left lower lobe. After air insufflations, 6 ml of bovine surfactant (calfactant) were instilled in each lobe. Chest fluoroscopy was done immediately after procedure and showed expansion of entire left lung with no pneumothorax. The procedure was well tolerated. The patient's symptoms and hypoxemia resolved soon after procedure. However, left lower lobe atelectasis recurred next day and persisted for 6 days despite treatments with chest physical therapy, systemic steroids, oral azithromycin, nebulized dornase alpha, and endoscopic removal of secretions from left lower lobe. Bronchoscopic insufflation of left lower lobe was repeated resulting in immediate expansion of that lobe as demonstrated by intraoperative fluoroscopy. The patient was discharged home next day. This case suggests that brochoscopic lung insufflation can be safe and effective in treating acute lung collapse and in treating atelectasis which is refractory to conventional therapy. Copyright © 2012 Wiley Periodicals, Inc.

  6. Experimental validation of 2-D generalized geometric super resolved approach

    NASA Astrophysics Data System (ADS)

    Borkowski, Amikam; Zalevsky, Zeev; Cohen, Nadav; Hadas, Zadok; Marom, Emanuel; Javidi, Bahram

    2014-01-01

    In this paper, we generalize the method of using a 2-D moving binary random mask to overcome the geometrical resolution limitation of an imaging sensor. The spatial blurring is caused by the size of the imaging sensor pixels which yield insufficient spatial sampling. The mask is placed in an intermediate image plane and can be shifted in any direction while keeping the sensor as well as all other optical components fixed. Out of the set of images that are captured and registered, a high resolution image can be composed. In addition, this proposed approach reduces the amount of required computations and it has an improved robustness to spatial noise.

  7. Seventh international conference on time-resolved vibrational spectroscopy

    SciTech Connect

    Dyer, R.B.; Martinez, M.A.D.; Shreve, A.; Woodruff, W.H.

    1997-04-01

    The International Conference on Time-Resolved Vibrational Spectroscopy (TRVS) is widely recognized as the major international forum for the discussion of advances in this rapidly growing field. The 1995 conference was the seventh in a series that began at Lake Placid, New York, 1982. Santa Fe, New Mexico, was the site of the Seventh International Conference on Time-Resolved Vibrational Spectroscopy, held from June 11 to 16, 1995. TRVS-7 was attended by 157 participants from 16 countries and 85 institutions, and research ranging across the full breadth of the field of time-resolved vibrational spectroscopy was presented. Advances in both experimental capabilities for time-resolved vibrational measurements and in theoretical descriptions of time-resolved vibrational methods continue to occur, and several sessions of the conference were devoted to discussion of these advances and the associated new directions in TRVS. Continuing the interdisciplinary tradition of the TRVS meetings, applications of time-resolved vibrational methods to problems in physics, biology, materials science, and chemistry comprised a large portion of the papers presented at the conference.

  8. Pulmonary mass and multiple lung nodules mimicking a lung neoplasm as amiodarone-induced pulmonary toxicity.

    PubMed

    Rodríguez-García, J L.; García-Nieto, J C.; Ballesta, F; Prieto, E; Villanueva, M A.; Gallardo, J

    2001-07-01

    Amiodarone is an effective anti-arrhythmic agent. However, during long-term therapy, patients can develop severe adverse pulmonary reactions that are potentially life-threatening. A case of amiodarone-induced pulmonary toxicity is presented in a 78-year-old woman. She developed dyspnea and a pulmonary mass with associated multiple lung nodules mimicking a lung cancer following 5 years of treatment with amiodarone for atrial fibrillation. After drug withdrawal, and without any additional treatment, clinical and radiological improvement was observed, and radiological findings resolved completely within 6 months.

  9. Epidemiology of Lung Cancer

    PubMed Central

    Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

    2013-01-01

    Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

  10. Approaches to resolving trade disputes.

    PubMed

    Wilson, D W; Thiermann, A B

    2003-08-01

    The authors discuss the various approaches to resolving trade disputes available to Member Countries of the OIE (World organisation for animal health). The paper first describes the rights and obligations of Member Countries in setting health measures for the importation of animals and animal products, according to the provisions of the World Trade Organization (WTO) Agreement on the Application of Sanitary and Phytosanitary Measures (the SPS Agreement). The authors indicate how OIE standards may be used to set import measures and introduce issues such as equivalence and the use of provisional measures, which are both areas of potential conflict. The authors then describe the options available for resolving disputes--bilateral discussions, mediation through the OIE, the use of the WTO SPS Committee and the formal WTO dispute settlement process, discussing the advantages and disadvantages of each.

  11. Rotationally resolved electronic spectroscopy of 5-methoxyindole.

    PubMed

    Brand, Christian; Oeltermann, Olivia; Pratt, David; Weinkauf, Rainer; Meerts, W Leo; van der Zande, Wim; Kleinermanns, Karl; Schmitt, Michael

    2010-07-14

    Rotationally resolved electronic spectra of the vibrationless origin and of eight vibronic bands of 5-methoxyindole (5MOI) have been measured and analyzed using an evolutionary strategy approach. The experimental results are compared to the results of ab initio calculations. All vibronic bands can be explained by absorption of a single conformer, which unambiguously has been shown to be the anti-conformer from its rotational constants and excitation energy. For both anti- and syn-conformers, a (1)L(a)/(1)L(b) gap larger than 4000 cm(-1) is calculated, making the vibronic coupling between both states very small, thereby explaining why the spectrum of 5MOI is very different from that of the parent molecule, indole.

  12. Angle-resolved photoemission extended fine structure

    SciTech Connect

    Barton, J.J.

    1985-03-01

    Measurements of the Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) from the S(1s) core level of a c(2 x 2)S/Ni(001) are analyzed to determine the spacing between the S overlayer and the first and second Ni layers. ARPEFS is a type of photoelectron diffraction measurement in which the photoelectron kinetic energy is swept typically from 100 to 600 eV. By using this wide range of intermediate energies we add high precision and theoretical simplification to the advantages of the photoelectron diffraction technique for determining surface structures. We report developments in the theory of photoelectron scattering in the intermediate energy range, measurement of the experimental photoemission spectra, their reduction to ARPEFS, and the surface structure determination from the ARPEFS by combined Fourier and multiple-scattering analyses. 202 refs., 67 figs., 2 tabs.

  13. Resolving Phase Ambiguities In OQPSK

    NASA Technical Reports Server (NTRS)

    Nguyen, Tien M.

    1991-01-01

    Improved design for modulator and demodulator in offset-quaternary-phase-key-shifting (OQPSK) communication system enables receiver to resolve ambiguity in estimated phase of received signal. Features include unique-code-word modulation and detection and digital implementation of Costas loop in carrier-recovery subsystem. Enchances performance of carrier-recovery subsystem, reduces complexity of receiver by removing redundant circuits from previous design, and eliminates dependence of timing in receiver upon parallel-to-serial-conversion clock.

  14. Extended Deterrence and Communicating Resolve

    DTIC Science & Technology

    2009-01-01

    being interpreted as bluffs indicating a lack of U.S. resolve. The U.S. President should, therefore, eschew the use of TLAM/N for signaling. The...example, Earl C. Ravenal , "Counterforce and Alliance: The Ultimate Connection," International Security 6, No. 4 (Spring 1982): 26-43. 2. William J...policy/dod/npr.htm. 13. Ravenal , "Counterforce and Alliance: The Ultimate Connection." 14. Moreover, damage limitation capabilities are not cost

  15. Resolved conifolds in supergravity solutions

    SciTech Connect

    Ghezelbash, A. M.

    2008-01-15

    We construct generalized 11D supergravity solutions of fully localized intersecting D2/D4 brane systems. These solutions are obtained by embedding six-dimensional resolved Eguchi-Hanson conifolds lifted to M-theory. We reduce these solutions to ten dimensions, obtaining new D-brane systems in type IIA supergravity. We discuss the limits in which the dynamics of the D2 brane decouples from the bulk for these solutions.

  16. Time-resolved photon emission from layered turbid media

    NASA Astrophysics Data System (ADS)

    Hielscher, Andreas H.; Liu, Hanli; Chance, Britton; Tittel, Frank K.; Jacques, Steven L.

    1996-02-01

    We present numerical and experimental results of time-resolved emission profiles from various layered turbid media. Numerical solutions determined by time-resolved Monte Carlo simulations are compared with measurements on layered-tissue phantoms made from gelatin. In particular, we show that in certain cases the effects of the upper layers can be eliminated. As a practical example, these results are used to analyze in vivo measurements on the human head. This demonstrates the influence of skin, skull, and meninges on the determination of the blood oxygenation in the brain.

  17. Time-resolved photon emission from layered turbid media

    SciTech Connect

    Hielscher, A.H.; Liu, H.; Chance, B.; Tittel, F.K.; Jacques, S.L.

    1996-02-01

    We present numerical and experimental results of time-resolved emission profiles from various layered turbid media. Numerical solutions determined by time-resolved Monte Carlo simulations are compared with measurements on layered-tissue phantoms made from gelatin. In particular, we show that in certain cases the effects of the upper layers can be eliminated. As a practical example, these results are used to analyze {ital in} {ital vivo} measurements on the human head. This demonstrates the influence of skin, skull, and meninges on the determination of the blood oxygenation in the brain. {copyright} {ital 1996 Optical Society of America.}

  18. Functional vascularized lung grafts for lung bioengineering

    PubMed Central

    Dorrello, N. Valerio; Guenthart, Brandon A.; O’Neill, John D.; Kim, Jinho; Cunningham, Katherine; Chen, Ya-Wen; Biscotti, Mauer; Swayne, Theresa; Wobma, Holly M.; Huang, Sarah X. L.; Snoeck, Hans-Willem; Bacchetta, Matthew; Vunjak-Novakovic, Gordana

    2017-01-01

    End-stage lung disease is the third leading cause of death worldwide, accounting for 400,000 deaths per year in the United States alone. To reduce the morbidity and mortality associated with lung disease, new therapeutic strategies aimed at promoting lung repair and increasing the number of donor lungs available for transplantation are being explored. Because of the extreme complexity of this organ, previous attempts at bioengineering functional lungs from fully decellularized or synthetic scaffolds lacking functional vasculature have been largely unsuccessful. An intact vascular network is critical not only for maintaining the blood-gas barrier and allowing for proper graft function but also for supporting the regenerative cells. We therefore developed an airway-specific approach to removing the pulmonary epithelium, while maintaining the viability and function of the vascular endothelium, using a rat model. The resulting vascularized lung grafts supported the attachment and growth of human adult pulmonary cells and stem cell–derived lung-specified epithelial cells. We propose that de-epithelialization of the lung with preservation of intact vasculature could facilitate cell therapy of pulmonary epithelium and enable bioengineering of functional lungs for transplantation. PMID:28875163

  19. Multiphoton microscopy as a diagnostic imaging modality for lung cancer

    NASA Astrophysics Data System (ADS)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Peters, Rachel M.; Weiss, Robert S.; Webb, Watt W.

    2010-02-01

    Lung cancer is the leading killer among all cancers for both men and women in the US, and is associated with one of the lowest 5-year survival rates. Current diagnostic techniques, such as histopathological assessment of tissue obtained by computed tomography guided biopsies, have limited accuracy, especially for small lesions. Early diagnosis of lung cancer can be improved by introducing a real-time, optical guidance method based on the in vivo application of multiphoton microscopy (MPM). In particular, we hypothesize that MPM imaging of living lung tissue based on twophoton excited intrinsic fluorescence and second harmonic generation can provide sufficient morphologic and spectroscopic information to distinguish between normal and diseased lung tissue. Here, we used an experimental approach based on MPM with multichannel fluorescence detection for initial discovery that MPM spectral imaging could differentiate between normal and neoplastic lung in ex vivo samples from a murine model of lung cancer. Current results indicate that MPM imaging can directly distinguish normal and neoplastic lung tissues based on their distinct morphologies and fluorescence emission properties in non-processed lung tissue. Moreover, we found initial indication that MPM imaging differentiates between normal alveolar tissue, inflammatory foci, and lung neoplasms. Our long-term goal is to apply results from ex vivo lung specimens to aid in the development of multiphoton endoscopy for in vivo imaging of lung abnormalities in various animal models, and ultimately for the diagnosis of human lung cancer.

  20. Warning Signs of Lung Disease

    MedlinePlus

    ... Warning Signs of Lung Disease Warning Signs of Lung Disease A nagging cough or slight wheeze may ... prepare for you next office visit. Questions about Lung Health? Call our Lung HelpLine. Get free counseling ...

  1. Lung needle biopsy

    MedlinePlus

    ... if you have certain lung diseases such as emphysema. Usually, a collapsed lung after a biopsy does ... any type Bullae (enlarged alveoli that occur with emphysema) Cor pulmonale (condition that causes the right side ...

  2. Lungs and Respiratory System

    MedlinePlus

    ... Your 1- to 2-Year-Old Lungs and Respiratory System KidsHealth > For Parents > Lungs and Respiratory System A ... ll have taken at least 600 million breaths. Respiratory System Basics All of this breathing couldn't happen ...

  3. Ex vivo lung perfusion

    PubMed Central

    Machuca, Tiago N.

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972

  4. Lung cancer screening update

    PubMed Central

    Dhillon, Samjot Singh; Loewen, Gregory; Jayaprakash, Vijayvel; Reid, Mary E.

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality globally and the American cancer society estimates approximately 226,160 new cases and 160,340 deaths from lung cancer in the USA in the year 2012. The majority of lung cancers are diagnosed in the later stages which impacts the overall survival. The 5-year survival rate for pathological st age IA lung cancer is 73% but drops to only 13% for stage IV. Thus, early detection through screening and prevention are the keys to reduce the global burden of lung cancer. This article discusses the current state of lung cancer screening, including the results of the National Lung Cancer Screening Trial, the consideration of implementing computed tomography screening, and a brief overview of the role of bronchoscopy in early detection and potential biomarkers that may aid in the early diagnosis of lung cancer. PMID:23599684

  5. Interstitial Lung Disease

    MedlinePlus

    ... Critical Care & Sleep Medicine Interstitial Lung Disease Program Sarcoidosis Program Autoimmune Lung Center Rebecca C. Keith, MD, ... Syndromes Hypersensitivity Pneumonitis LAM Lupus Rheumatoid Arthritis (RA) Sarcoidosis Overview Scleroderma (SSC) Systemic Vasculitis Reasons to Visit ...

  6. Lung gallium scan

    MedlinePlus

    ... the lungs. This is most often due to sarcoidosis or a certain type of pneumonia. Normal Results ... it may mean any of the following problems: Sarcoidosis (disease in which inflammation occurs in the lungs ...

  7. Concept of proton radiography using energy resolved dose measurement.

    PubMed

    Bentefour, El H; Schnuerer, Roland; Lu, Hsiao-Ming

    2016-08-21

    Energy resolved dosimetry offers a potential path to single detector based proton imaging using scanned proton beams. This is because energy resolved dose functions encrypt the radiological depth at which the measurements are made. When a set of predetermined proton beams 'proton imaging field' are used to deliver a well determined dose distribution in a specific volume, then, at any given depth x of this volume, the behavior of the dose against the energies of the proton imaging field is unique and characterizes the depth x. This concept applies directly to proton therapy scanning delivery methods (pencil beam scanning and uniform scanning) and it can be extended to the proton therapy passive delivery methods (single and double scattering) if the delivery of the irradiation is time-controlled with a known time-energy relationship. To derive the water equivalent path length (WEPL) from the energy resolved dose measurement, one may proceed in two different ways. A first method is by matching the measured energy resolved dose function to a pre-established calibration database of the behavior of the energy resolved dose in water, measured over the entire range of radiological depths with at least 1 mm spatial resolution. This calibration database can also be made specific to the patient if computed using the patient x-CT data. A second method to determine the WEPL is by using the empirical relationships between the WEPL and the integral dose or the depth at 80% of the proximal fall off of the energy resolved dose functions in water. In this note, we establish the evidence of the fundamental relationship between the energy resolved dose and the WEPL at the depth of the measurement. Then, we illustrate this relationship with experimental data and discuss its imaging dynamic range for 230 MeV protons.

  8. Concept of proton radiography using energy resolved dose measurement

    NASA Astrophysics Data System (ADS)

    Bentefour, El H.; Schnuerer, Roland; Lu, Hsiao-Ming

    2016-08-01

    Energy resolved dosimetry offers a potential path to single detector based proton imaging using scanned proton beams. This is because energy resolved dose functions encrypt the radiological depth at which the measurements are made. When a set of predetermined proton beams ‘proton imaging field’ are used to deliver a well determined dose distribution in a specific volume, then, at any given depth x of this volume, the behavior of the dose against the energies of the proton imaging field is unique and characterizes the depth x. This concept applies directly to proton therapy scanning delivery methods (pencil beam scanning and uniform scanning) and it can be extended to the proton therapy passive delivery methods (single and double scattering) if the delivery of the irradiation is time-controlled with a known time-energy relationship. To derive the water equivalent path length (WEPL) from the energy resolved dose measurement, one may proceed in two different ways. A first method is by matching the measured energy resolved dose function to a pre-established calibration database of the behavior of the energy resolved dose in water, measured over the entire range of radiological depths with at least 1 mm spatial resolution. This calibration database can also be made specific to the patient if computed using the patient x-CT data. A second method to determine the WEPL is by using the empirical relationships between the WEPL and the integral dose or the depth at 80% of the proximal fall off of the energy resolved dose functions in water. In this note, we establish the evidence of the fundamental relationship between the energy resolved dose and the WEPL at the depth of the measurement. Then, we illustrate this relationship with experimental data and discuss its imaging dynamic range for 230 MeV protons.

  9. Lung cancer prevention.

    PubMed

    Slatore, Christopher; Sockrider, Marianna

    2014-11-15

    Lung cancer is a common form of cancer.There are things you can do to lower your risk of lung cancer. Stop smoking tobacco. Ask your health care provider for help in quitting, including use of medicines to help with nicotine dependence. discuss with your healthcare provider,what you are taking or doing to decrease your risk for lung cancer

  10. Lungs and Respiratory System

    MedlinePlus

    ... A Week of Healthy Breakfasts Shyness Lungs and Respiratory System KidsHealth > For Teens > Lungs and Respiratory System A ... didn't breathe, you couldn't live. Lungs & Respiratory System Basics Each day we breathe about 20,000 ...

  11. Resolving the formation of modern Chladni figures

    NASA Astrophysics Data System (ADS)

    Tuan, P. H.; Tung, J. C.; Liang, H. C.; Chiang, P. Y.; Huang, K. F.; Chen, Y. F.

    2015-09-01

    The resonant spectrum of a thin plate driven with a mechanical oscillator is precisely measured to distinguish modern Chladni figures (CFs) observed at the resonant frequencies from classical CFs observed at the non-resonant frequencies. Experimental results reveal that modern CFs generally display an important characteristic of avoided crossings of nodal lines, whereas the nodal lines of classical CFs form a regular grid. The formation of modern CFs and the resonant frequency spectrum are resolved with a theoretical model that characterizes the interaction between the plate and the driving source into the inhomogeneous Kirchhoff-Love equation. The derived formula for determining resonant frequencies is shown to be exactly identical to the meromorphic function given in singular billiards that deals with the coupling strength on the transition between integrable and chaotic features. The good agreement between experimental results and theoretical predictions verifies the significant role of the strong-coupling effect in the formation of modern CFs. More importantly, it is confirmed that the apparatus for generating modern CFs can be developed to serve as an expedient system for exploring the nodal domains of chaotic wave functions as well as the physics of the strong coupling with a point scatterer.

  12. Inconsistencies in findings from the early lung cancer action project studies of lung cancer screening.

    PubMed

    Bach, Peter B

    2011-07-06

    Long-standing guidelines against screening high-risk individuals for lung cancer may change following the publication of the randomized National Lung Screening Trial (NLST), which shows a benefit of computed tomography compared with chest x-ray screening. Guideline panels will likely also seek additional information from nonrandomized studies of computed tomography screening, such as the Early Lung Cancer Action Project (ELCAP). However, for the ELCAP findings to be incorporated into new guidelines, some inconsistencies in the published data should first be resolved. Specifically, some of the reports from ELCAP appear to contradict others in terms of important endpoints, and several findings from ELCAP appear to be statistically improbable or outliers when compared with analyses and studies by other research groups. Clarification of both internal and external inconsistencies is a prerequisite for evaluation of the body of work published by ELCAP investigators.

  13. The lung in space

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim

    2005-01-01

    The lung is exquisitely sensitive to gravity, which induces gradients in ventilation, blood flow, and gas exchange. Studies of lungs in microgravity provide a means of elucidating the effects of gravity. They suggest a mechanism by which gravity serves to match ventilation to perfusion, making for a more efficient lung than anticipated. Despite predictions, lungs do not become edematous, and there is no disruption to, gas exchange in microgravity. Sleep disturbances in microgravity are not a result of respiratory-related events; obstructive sleep apnea is caused principally by the gravitational effects on the upper airways. In microgravity, lungs may be at greater risk to the effects of inhaled aerosols.

  14. The lung in space

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim

    2005-01-01

    The lung is exquisitely sensitive to gravity, which induces gradients in ventilation, blood flow, and gas exchange. Studies of lungs in microgravity provide a means of elucidating the effects of gravity. They suggest a mechanism by which gravity serves to match ventilation to perfusion, making for a more efficient lung than anticipated. Despite predictions, lungs do not become edematous, and there is no disruption to, gas exchange in microgravity. Sleep disturbances in microgravity are not a result of respiratory-related events; obstructive sleep apnea is caused principally by the gravitational effects on the upper airways. In microgravity, lungs may be at greater risk to the effects of inhaled aerosols.

  15. Perioperative Lung Protection Provided by High-Dose Ambroxol in Patients with Lung Cancer.

    PubMed

    Wang, Xin; Wang, Lei; Wang, Huayong; Zhang, Hao

    2015-11-01

    The purpose is to observe the clinical effect of large doses of ambroxol hydrochloride in lung protection during the perioperative period of lung cancer operation. Fifty-six lung cancer patients who have undergone open-thoracic pulmonary lobectomy were divided randomly into two groups, and were given normal and large doses of ambroxol hydrochloride, respectively, during their perioperative period. Statistics based on post-operation clinical observations were analyzed in terms of ease of expectoration and expectoration properties, duration of antibiotics dependence, occurrence of lung complications, and adverse reactions related to ambroxol hydrochloride. On the third and the seventh day, the experimental group showed signs of improvement in terms of ease of expectoration and expectoration properties, compared with the controlled group. In terms of occurrence of post-operation lung complications and duration of antibiotics dependence, the experimental group also performed better. Using large doses of ambroxol hydrochloride would result in better clinical effects than using normal doses in preventing post-operation complications, and its clinical value in lung protection during lung cancer perioperative period calls for further research and promotion.

  16. ATM protein is deficient in over 40% of lung adenocarcinomas.

    PubMed

    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

    2016-09-06

    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  17. Bilateral lavage with diluted surfactant improves lung function after unilateral lung contusion in pigs.

    PubMed

    Strohmaier, Wolfgang; Trupka, Arnold; Pfeiler, Claudia; Thurnher, Martin; Khakpour, Zafar; Gippner-Steppert, Cornelia; Jochum, Marianne; Redl, Heinz

    2005-10-01

    This study evaluates the effects of bronchoalveolar lavage with diluted surfactant on unilateral lung contusion-induced lung dysfunction. Randomized prospective animal study. An animal laboratory. Twenty adult pigs, weighing 25-35 kg. Animals were randomly assigned to controls and surfactant treatment. Bilateral lavage with surfactant treatment began 30 mins after unilateral lung contusion. Then 25 mg/kg of body weight diluted Curosurf (5 mg/mL) was applied in a volume of 5 mL/kg of body weight. Observation time was 8 hrs postinjury. The Pao2/Fio2 ratio fell from 500 to 250 and then recovered gradually in controls and surfactant-treated pigs. After another 4 hrs, the Pao2/Fio2 ratio deteriorated again in controls, but not in surfactant-treated animals. Total compliance fell by 50% after injury but was completely restored by surfactant treatment. Lung contusion increased the median number of neutrophils in bronchoalveolar lavage fluid from 2% to 30% of total cells and peaked >60% at 480 mins in the contused lungs of control pigs. Surfactant-treated pigs had 40% neutrophils at 480 mins without reaching significant difference to controls. The leukocyte neutral proteinase inhibitor increased to 500 ng/mL at 30 mins postinjury in the contused lungs and increased to 2000 ng/mL after surfactant treatment. Bilateral bronchoalveolar lavage with diluted surfactant can effectively improve lung function after experimental unilateral lung contusion in pigs.

  18. Advances in artificial lungs.

    PubMed

    Ota, Kei

    2010-04-01

    Artificial lungs have already been developed as complete artificial organs, and results of many investigations based on innovative concepts have been reported continuously. In open-heart surgery, artificial lungs are used for extracorporeal circulation to maintain gas exchange, and the commercial products currently available perform adequately, including providing for antithrombogenicity. However, patients after cardiopulmonary arrest or severe respiratory/circulatory failure have required long-term assist with extracorporeal membrane oxygenation (ECMO). The number of artificial lungs used for ECMO in those cases has shown significant growth in recent years. Therefore, it is expected that durability and antithrombogenicity will ensure the prolonged use of an artificial lung for several weeks or months. Furthermore, interests in research are shifting to use of oxygenators as a bridge to lung transplantation and an implantable artificial lung. This paper discusses recent advances in artificial lungs, focusing on the current state and on trends in research and development.

  19. [Lung cancer screening].

    PubMed

    Sánchez González, M

    2014-01-01

    Lung cancer is a very important disease, curable in early stages. There have been trials trying to show the utility of chest x-ray or computed tomography in Lung Cancer Screening for decades. In 2011, National Lung Screening Trial results were published, showing a 20% reduction in lung cancer mortality in patients with low dose computed tomography screened for three years. These results are very promising and several scientific societies have included lung cancer screening in their guidelines. Nevertheless we have to be aware of lung cancer screening risks, such as: overdiagnosis, radiation and false positive results. Moreover, there are many issues to be solved, including choosing the appropriate group to be screened, the duration of the screening program, intervals between screening and its cost-effectiveness. Ongoing trials will probably answer some of these questions. This article reviews the current evidence on lung cancer screening.

  20. Resolving the Shock Wave Profile in Viscous Fluids

    NASA Astrophysics Data System (ADS)

    Jordan, Kenneth; Borg, John

    2011-06-01

    Capturing and modeling shock wave profiles has a long history in computational analysis. Often artificial irreversibilities and/or smearing schemes are implemented in order to stabilize and resolve the shock. This work presents a direct numeric simulation of the full Navier-Stokes equations where the shock profile is completely resolved without the use of artificial viscosity or shock smearing techniques. Several viscosity models are employed to study the role of viscosity on this second order accurate finite difference scheme. The results are compared to an analytic solutions and experimental results. The results indicated that the shock front thickness and entropy production are in good agreement with simple analytic solutions and experimental results. The extension of this technique to solid and granular materials will be discussed.

  1. Microsecond-resolved SDR-based cavity ring down ellipsometry.

    PubMed

    Sofikitis, D; Spiliotis, A K; Stamataki, K; Katsoprinakis, G E; Bougas, L; Samartzis, P C; Loppinet, B; Rakitzis, T P; Surligas, M; Papadakis, S

    2015-06-20

    We present an experimental apparatus that allows microsecond-resolved ellipsometric and absorption measurements. The apparatus is based on an optical cavity containing a Dove prism, in which light undergoes total internal reflection (TIR), while the data acquisition is based on software defined radio technology and custom-built drivers. We demonstrate the ability to sense rapid variations in the refractive index above the TIR interface for arbitrarily long times with a temporal resolution of at least 2 μs.

  2. Resolving conflicts: principles and practice.

    PubMed

    Gill, S L

    1995-04-01

    Physicians and other medical professionals undergo extensive professional training for the privilege of obtaining their professional licenses. For most physicians, clinical training is conducted in extremely competitive circumstances. Many physicians endorse competition as an appropriate method for producing greater individual and collective competence within the profession. Competition, however, is a very limited way to resolve conflicts. And, in the current environment of greater resource restrictions and reform, the competitive model, at best, seems short-sighted. Many of the current relationships involving physicians and others are transitional, involving various partners in numerous practice and professional relationships. For example, medical practices are merging; hospitals are engaging physicians in numerous business structures, even employment. However, longer term relationships are enhanced by mutual respect and collaboration, rather than chronic competition to "win" one's rights over another. Thus, the need among physicians to enhance their conflict resolution skills is expanded in today's environment.

  3. Resolving thermoelectric "paradox" in superconductors.

    PubMed

    Shelly, Connor D; Matrozova, Ekaterina A; Petrashov, Victor T

    2016-02-01

    For almost a century, thermoelectricity in superconductors has been one of the most intriguing topics in physics. During its early stages in the 1920s, the mere existence of thermoelectric effects in superconductors was questioned. In 1944, it was demonstrated that the effects may occur in inhomogeneous superconductors. Theoretical breakthrough followed in the 1970s, when the generation of a measurable thermoelectric magnetic flux in superconducting loops was predicted; however, a major crisis developed when experiments showed puzzling discrepancies with the theory. Moreover, different experiments were inconsistent with each other. This led to a stalemate in bringing theory and experiment into agreement. With this work, we resolve this stalemate, thus solving this long-standing "paradox," and open prospects for exploration of novel thermoelectric phenomena predicted recently.

  4. Plasma proteomics of lung cancer by a linkage of multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis.

    PubMed

    Okano, Tetsuya; Kondo, Tadashi; Kakisaka, Tatsuhiko; Fujii, Kiyonaga; Yamada, Masayo; Kato, Harubumi; Nishimura, Toshihide; Gemma, Akihiko; Kudoh, Shoji; Hirohashi, Setsuo

    2006-07-01

    To investigate aberrant plasma proteins in lung cancer, we compared the proteomic profiles of serum from five lung cancer patients and from four healthy volunteers. Immuno-affinity chromatography was used to deplete highly abundant plasma proteins, and the resulting plasma samples were separated into eight fractions by anion-exchange chromatography. Quantitative protein profiles of the fractionated samples were generated by two-dimensional difference gel electrophoresis, in which the experimental samples and the internal control samples were labeled with different dyes and co-separated by two-dimensional polyacrylamide gel electrophoresis. This approach succeeded in resolving 3890 protein spots. For 364 of the protein spots, the expression level in lung cancer was more than twofold different from that in the healthy volunteers. These differences were statistically significant (Student's t-test, p-value less than 0.05). Mass spectrometric protein identification revealed that the 364 protein spots corresponded to 58 gene products, including the classical plasma proteins and the tissue-leakage proteins catalase, clusterin, ficolin, gelsolin, lumican, tetranectin, triosephosphate isomerase and vitronectin. The combination of multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis provides a valuable tool for serum proteomics in lung cancer.

  5. 75 FR 66771 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-29

    ... HUMAN SERVICES National Institutes of Health National Heart, Lung, and Blood Institute; Notice of Closed.... ] Name of Committee: National Heart, Lung, and Blood Institute Special Emphasis Panel; Centers for Advanced Diagnostics and Experimental Therapeutics in Lung Diseases (CADET I). Date: November 18-19, 2010...

  6. The effect of inhalation of Citrus sinensis flowers and Mentha spicata leave essential oils on lung function and exercise performance: a quasi-experimental uncontrolled before-and-after study.

    PubMed

    Jaradat, Nidal Amin; Al Zabadi, Hamzeh; Rahhal, Belal; Hussein, Azmi Mahmoud Ali; Mahmoud, Jamal Shaker; Mansour, Basel; Khasati, Ahmad Ibrahim; Issa, Abdelkhaleq

    Recently, there has been an increased interest in the effects of essential oils on athletic performances and other physiological effects. This study aimed to assess the effects of Citrus sinensis flower and Mentha spicata leaves essential oils inhalation in two different groups of athlete male students on their exercise performance and lung function. Twenty physical education students volunteered to participate in the study. The subjects were randomly assigned into two groups: Mentha spicata and Citrus sinensis (ten participants each). One group was nebulized by Citrus sinensis flower oil and the other by Mentha spicata leaves oil in a concentration of (0.02 ml/kg of body mass) which was mixed with 2 ml of normal saline for 5 min before a 1500 m running tests. Lung function tests were measured using a spirometer for each student pre and post nebulization giving the same running distance pre and post oils inhalation. A lung function tests showed an improvement on the lung status for the students after inhaling of the oils. Interestingly, there was a significant increase in Forced Expiratory Volume in the first second and Forced Vital Capacity after inhalation for the both oils. Moreover significant reductions in the means of the running time were observed among these two groups. The normal spirometry results were 50 %, while after inhalation with M. spicata oil the ratio were 60 %. Our findings support the effectiveness of M. spicata and C. sinensis essential oils on the exercise performance and respiratory function parameters. However, our conclusion and generalisability of our results should be interpreted with caution due to small sample size and lack of control groups, randomization or masking. We recommend further investigations to explain the mechanism of actions for these two essential oils on exercise performance and respiratory parameters. ISRCTN10133422, Registered: May 3, 2016.

  7. Metabolism and Skeletal Muscle Homeostasis in Lung Disease.

    PubMed

    Ceco, Ermelinda; Weinberg, Samuel E; Chandel, Navdeep S; Sznajder, Jacob I

    2017-07-01

    There is increased awareness that patients with lung diseases develop muscle dysfunction. Muscle dysfunction is a major contributor to a decreased quality of life in patients with chronic pulmonary diseases. Furthermore, muscle dysfunction exacerbates lung disease outcome, as a decrease in muscle mass and function are associated with increased morbidity, often long after critical illness or lung disease has been resolved. As we are learning more about the role of metabolism in health and disease, we are appreciating more the direct role of metabolism in skeletal muscle homeostasis. Altered metabolism is associated with numerous skeletal muscle pathologies and, conversely, skeletal muscle diseases are associated with significant changes in metabolic pathways. In this review, we highlight the role of metabolism in the regulation of skeletal muscle homeostasis. Understanding the metabolic pathways that underlie skeletal muscle wasting is of significant clinical interest for critically ill patients as well as patients with chronic lung disease, in which proper skeletal muscle function is essential to disease outcome.

  8. Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume.

    PubMed

    Vande Velde, Greetje; Poelmans, Jennifer; De Langhe, Ellen; Hillen, Amy; Vanoirbeek, Jeroen; Himmelreich, Uwe; Lories, Rik J

    2016-01-01

    In vivo lung micro-computed tomography (micro-CT) is being increasingly embraced in pulmonary research because it provides longitudinal information on dynamic disease processes in a field in which ex vivo assessment of experimental disease models is still the gold standard. To optimize the quantitative monitoring of progression and therapy of lung diseases, we evaluated longitudinal changes in four different micro-CT-derived biomarkers [aerated lung volume, lung tissue (including lesions) volume, total lung volume and mean lung density], describing normal development, lung infections, inflammation, fibrosis and therapy. Free-breathing mice underwent micro-CT before and repeatedly after induction of lung disease (bleomycin-induced fibrosis, invasive pulmonary aspergillosis, pulmonary cryptococcosis) and therapy (imatinib). The four lung biomarkers were quantified. After the last time point, we performed pulmonary function tests and isolated the lungs for histology. None of the biomarkers remained stable during longitudinal follow-up of adult healthy mouse lungs, implying that biomarkers should be compared with age-matched controls upon intervention. Early inflammation and progressive fibrosis led to a substantial increase in total lung volume, which affects the interpretation of aerated lung volume, tissue volume and mean lung density measures. Upon treatment of fibrotic lung disease, the improvement in aerated lung volume and function was not accompanied by a normalization of the increased total lung volume. Significantly enlarged lungs were also present in models of rapidly and slowly progressing lung infections. The data suggest that total lung volume changes could partly reflect a compensatory mechanism that occurs during disease progression in mice. Our findings underscore the importance of quantifying total lung volume in addition to aerated lung or lesion volumes to accurately document growth and potential compensatory mechanisms in mouse models of lung

  9. Efficient, physiologically realistic lung airflow simulations.

    PubMed

    Walters, D Keith; Burgreen, Greg W; Lavallee, David M; Thompson, David S; Hester, Robert L

    2011-10-01

    One of the key challenges for computational fluid dynamics (CFD) simulations of human lung airflow is the sheer size and complexity of the complete, multiscale geometry of the bronchopulmonary tree. Since 3-D CFD simulations of the full airway tree are currently intractable, researchers have proposed reduced geometry models in which multiple airway paths are truncated downstream of the first few generations. This paper investigates a recently proposed method for closing the CFD model by application of physiologically correct boundary conditions at truncated outlets. A realistic, reduced geometry model of the lung airway based on CT data has been constructed up to generation 18, including extrathoracic, bronchi, and bronchiole regions. Results indicate that the new method yields reasonable results for pressure drop through the airway, at a small fraction of the cost of fully resolved simulations.

  10. Micro-imaging of the Mouse Lung via MRI

    NASA Astrophysics Data System (ADS)

    Wang, Wei

    Quantitative measurement of lung microstructure is of great significance in assessment of pulmonary disease, particularly in the earliest stages. Conventional stereological assessment of ex-vivo fixed tissue specimens under the microscope has a long and successful tradition and is regarded as a gold standard, but the invasive nature limits its applications and the practicality of use in longitudinal studies. The technique for diffusion MRI-based 3He lung morphometry was previously developed and validated for human lungs, and was recently extended to ex-vivo mouse lungs. The technique yields accurate, quantitative information about the microstructure and geometry of acinar airways. In this dissertation, the 3He lung morphometry technique is for the first time successfully implemented for in-vivo studies of mice. It can generate spatially-resolved maps of parameters that reveal the microstructure of mouse lung. Results in healthy mice indicate excellent agreement between in-vivo morphometry via 3He MRI and microscopic morphometry after sacrifice. The implementation and validation of 3He morphometry in healthy mice open up new avenues for application of the technique as a precise, noninvasive, in-vivo biomarker of changes in lung microstructure, within various mouse models of lung disease. We have applied 3He morphometry to the Sendai mouse model of lung disease. Specifically, the Sendai-virus model of chronic obstructive lung disease has demonstrated an innate immune response in mouse airways that exhibits similarities to the chronic airway inflammation in human COPD and asthma, but the effect on distal lung parenchyma had not been investigated. We imaged the time course and regional distribution of mouse lung microstructural changes in vivo after Sendai virus (SeV) infection with 1H and 3He diffusion MRI. 1H MR images detected the SeV-induced pulmonary inflammation in vivo and 3He lung morphometry showed modest increase in alveolar duct radius distal to airway

  11. miR-34a Inhibits Lung Fibrosis by Inducing Lung Fibroblast Senescence.

    PubMed

    Cui, Huachun; Ge, Jing; Xie, Na; Banerjee, Sami; Zhou, Yong; Antony, Veena B; Thannickal, Victor J; Liu, Gang

    2017-02-01

    Cellular senescence has been implicated in diverse pathologies. However, there is conflicting evidence regarding the role of this process in tissue fibrosis. Although dysregulation of microRNAs is a key mechanism in the pathogenesis of lung fibrosis, it is unclear whether microRNAs function by regulating cellular senescence in the disease. In this study, we found that miR-34a demonstrated greater expression in the lungs of patients with idiopathic pulmonary fibrosis and in mice with experimental pulmonary fibrosis, with its primary localization in lung fibroblasts. More importantly, miR-34a was up-regulated significantly in both human and mouse lung myofibroblasts. We found that mice with miR-34a ablation developed more severe pulmonary fibrosis than did wild-type animals after fibrotic lung injury. Mechanistically, we found that miR-34a induced a senescent phenotype in lung fibroblasts because this microRNA increased senescence-associated β-galactosidase activity, enhanced expression of senescence markers, and decreased cell proliferative capacities. Consistently, we found that primary lung fibroblasts from fibrotic lungs of miR-34a-deficient mice had a diminished senescent phenotype and enhanced resistance to apoptosis as compared with those from wild-type animals. We also identified multiple miR-34a targets that likely mediated its activities in inducing senescence in lung fibroblasts. In conclusion, our data suggest that miR-34a functions through a negative feedback mechanism to restrain fibrotic response in the lungs by promoting senescence of pulmonary fibroblasts.

  12. ICAM-1-dependent and ICAM-1-independent neutrophil lung infiltration by porcine reproductive and respiratory syndrome virus infection.

    PubMed

    Liu, Jie; Hou, Make; Yan, Meiping; Lü, Xinhui; Gu, Wei; Zhang, Songlin; Gao, Jianfeng; Liu, Bang; Wu, Xiaoxiong; Liu, Guoquan

    2015-08-01

    Neutrophils are innate immune cells that play a crucial role in the first line of host defense. It is also known that neutrophil lung recruitment and infiltration may cause lung injury. The roles of neutrophils in virus infection-induced lung injury are not clear. We explore the mechanisms of neutrophil lung infiltration and the potential biomarkers for lung injury in a swine model of lung injury caused by natural or experimental porcine reproductive and respiratory syndrome virus (PRRSV) infection. Neutrophil lung infiltration was determined by measurement of myeloperoxidase expression and enzyme activity of lung tissues. Myeloperoxidase expression and enzyme activity were dramatically increased in the naturally and experimentally infected lung tissues. Chemokine analysis by quantitative PCR and ELISA showed that IL-8 expression was increased in both infections, while monocyte chemoattractant protein-1 expression was increased only in experimentally infected lung tissues. Expression of the cell adhesion molecules VCAM-1 and ICAM-1 was measured by quantitative PCR and Western blotting. VCAM-1 expression was increased in experimentally and naturally infected lungs, whereas ICAM-1 expression was increased only in the naturally infected lung samples. Our results suggest that neutrophil lung infiltrations in the infected animals are both ICAM-1- and -independent and that combined expression of VCAM-1 and IL-8 may serve as the biomarker for lung injury induced by virus infection. Copyright © 2015 the American Physiological Society.

  13. Resolving Seamounts in Satellite Altimetry

    NASA Astrophysics Data System (ADS)

    Marks, K. M.; Smith, W. H.

    2006-12-01

    We have examined three factors influencing the use of satellite altimeter data to map seamounts and guyots in the deep ocean: (1) the resolution of seamount and guyot gravity anomalies by altimetry; (2) the non-linearity of the relationship between gravity and bathymetry; and (3) the homogeneity of the mass density within the seamount or guyot. When altimeter data are used to model the marine gravity anomaly field the result may have limited resolution due to noise levels in the altimeter data, track spacing of the satellite profiles, inclination angles of the orbits, and filters used to combine and interpolate the data (Sandwell and Smith, JGR, 1997). We compared the peak-to-trough amplitude of gravity anomalies in Sandwell and Smith`'s version 15.1 field to peak-to-trough amplitudes measured by gravimeters on board ships. The satellite gravity field amplitudes match ship measurements well over seamounts and guyots having volumes exceeding ~2000 km3. Over smaller volume seamounts, where the anomalies have most of their power at quite short wavelengths, the satellite field under-estimates the anomaly amplitude. If less filtering could be done, or a new mission with a lower noise level were flown, more of the anomalies associated with small seamounts might be resolved. Smith and Sandwell (Science, 1997) predicted seafloor topography from altimetric gravity assuming that the density of seafloor topography is nearly constant over ~100 km distances, and that the relationship between gravity and topography may be approximated by a liner filter over those distances. In fact, the true theoretical relationship is non-linear (Parker, Geophys. J. R. astr. Soc, 1972); it can be expressed as an N-th order expansion, with the N=1 term representing a linear filter and the N>1 terms accounting for higher-order corrections. We find that N=2 is a sufficient approximation at both seamounts and guyots. Constant density models of large volume guyots do not fit the observed gravity

  14. Lung cancer in women

    PubMed Central

    Barrera-Rodriguez, Raúl; Morales-Fuentes, Jorge

    2012-01-01

    Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer. PMID:28210127

  15. Alveolar edema fluid clearance and acute lung injury.

    PubMed

    Berthiaume, Yves; Matthay, Michael A

    2007-12-15

    Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na(+) and Cl(-) transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na(+) and Cl(-) transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of beta-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury.

  16. Linear dimensions and volumes of human lungs

    SciTech Connect

    Hickman, David P.

    2012-03-30

    TOTAL LUNG Capacity is defined as “the inspiratory capacity plus the functional residual capacity; the volume of air contained in the lungs at the end of a maximal inspiration; also equals vital capacity plus residual volume” (from MediLexicon.com). Within the Results and Discussion section of their April 2012 Health Physics paper, Kramer et al. briefly noted that the lungs of their experimental subjects were “not fully inflated.” By definition and failure to obtain maximal inspiration, Kramer et. al. did not measure Total Lung Capacity (TLC). The TLC equation generated from this work will tend to underestimate TLC and does not improve or update total lung capacity data provided by ICRP and others. Likewise, the five linear measurements performed by Kramer et. al. are only representative of the conditions of the measurement (i.e., not at-rest volume, but not fully inflated either). While there was significant work performed and the data are interesting, the data does not represent a maximal situation, a minimal situation, or an at-rest situation. Moreover, while interesting, the linear data generated by this study is limited by the conditions of the experiment and may not be fully comparative with other lung or inspiratory parameters, measures, or physical dimensions.

  17. Linear dimensions and volumes of human lungs

    DOE PAGES

    Hickman, David P.

    2012-03-30

    TOTAL LUNG Capacity is defined as “the inspiratory capacity plus the functional residual capacity; the volume of air contained in the lungs at the end of a maximal inspiration; also equals vital capacity plus residual volume” (from MediLexicon.com). Within the Results and Discussion section of their April 2012 Health Physics paper, Kramer et al. briefly noted that the lungs of their experimental subjects were “not fully inflated.” By definition and failure to obtain maximal inspiration, Kramer et. al. did not measure Total Lung Capacity (TLC). The TLC equation generated from this work will tend to underestimate TLC and does notmore » improve or update total lung capacity data provided by ICRP and others. Likewise, the five linear measurements performed by Kramer et. al. are only representative of the conditions of the measurement (i.e., not at-rest volume, but not fully inflated either). While there was significant work performed and the data are interesting, the data does not represent a maximal situation, a minimal situation, or an at-rest situation. Moreover, while interesting, the linear data generated by this study is limited by the conditions of the experiment and may not be fully comparative with other lung or inspiratory parameters, measures, or physical dimensions.« less

  18. Resolving controversy of unusually high refractive index of a tubulin

    NASA Astrophysics Data System (ADS)

    Krivosudský, O.; Dráber, P.; Cifra, M.

    2017-02-01

    The refractive index of a tubulin is an important parameter underlying fundamental electromagnetic and biophysical properties of microtubules – protein fibers essential for several cell functions including cell division. Yet, the only experimental data available in the current literature show values of the tubulin refractive index (n=2.36\\text{--}2.90) which are much higher than what the established theories predict based on the weighted contribution of the polarizability of individual amino acids constituting the protein. To resolve this controversy, we report here modeling and rigorous experimental analysis of the refractive index of a purified tubulin dimer. Our experimental data revealed that the refractive index of the tubulin is n=1.64 at wavelength 589 nm and 25 °C, that is much closer to the values predicted by the established theories than what the earlier experimental data provide.

  19. Spatially resolved electronic structure of twisted graphene

    NASA Astrophysics Data System (ADS)

    Yao, Qirong; van Bremen, Rik; Slotman, Guus J.; Zhang, Lijie; Haartsen, Sebastiaan; Sotthewes, Kai; Bampoulis, Pantelis; de Boeij, Paul L.; van Houselt, Arie; Yuan, Shengjun; Zandvliet, Harold J. W.

    2017-06-01

    We have used scanning tunneling microscopy and spectroscopy to resolve the spatial variation of the density of states of twisted graphene layers on top of a highly oriented pyrolytic graphite substrate. Owing to the twist a moiré pattern develops with a periodicity that is substantially larger than the periodicity of a single layer graphene. The twisted graphene layer has electronic properties that are distinctly different from that of a single layer graphene due to the nonzero interlayer coupling. For small twist angles (˜1∘-3 .5∘) the integrated differential conductivity spectrum exhibits two well-defined Van Hove singularities. Spatial maps of the differential conductivity that are recorded at energies near the Fermi level exhibit a honeycomb structure that is comprised of two inequivalent hexagonal sublattices. For energies | E -EF |>0.3 eV the hexagonal structure in the differential conductivity maps vanishes. We have performed tight-binding calculations of the twisted graphene system using the propagation method, in which a third graphene layer is added to mimic the substrate. This third layer lowers the symmetry and explains the development of the two hexagonal sublattices in the moiré pattern. Our experimental results are in excellent agreement with the tight-binding calculations.

  20. Angle resolved photoemission spectroscopy and surface states

    NASA Astrophysics Data System (ADS)

    Kar, Nikhiles

    2016-10-01

    Angle Resolved Photo Emission Spectroscopy (ARPES) has been a very effective tool to study the electronic states of solids, from simple metals to complex systems like cuprate superconductors. For photon energy in the range of 10 - 100 eV, it is a surface sensitive process as the free path of the photo emitted electrons is of the order of a few lattice parameters. However to interpret the experimental data one needs to have a theoretical foundation for the photoemission process. From the theory of photoemission it may be seen that one can get information about the state from which the electron has been excited. As the translational periodicity is broken normal to the surface, a new type of electron state in the forbidden energy gap can exist localized in the surface region. ARPES can reveal the existence and the property of such surface states. We shall also discuss briefly how the electromagnetic field of the photons are influenced by the presence of the surface and how one can try to take that into account in photoemission theory.

  1. Radiation-enhanced lung cancer progression in a transgenic mouse model of lung cancer is predictive of outcomes in human lung and breast cancer.

    PubMed

    Delgado, Oliver; Batten, Kimberly G; Richardson, James A; Xie, Xian-Jin; Gazdar, Adi F; Kaisani, Aadil A; Girard, Luc; Behrens, Carmen; Suraokar, Milind; Fasciani, Gail; Wright, Woodring E; Story, Michael D; Wistuba, Ignacio I; Minna, John D; Shay, Jerry W

    2014-03-15

    Carcinogenesis is an adaptive process between nascent tumor cells and their microenvironment, including the modification of inflammatory responses from antitumorigenic to protumorigenic. Radiation exposure can stimulate inflammatory responses that inhibit or promote carcinogenesis. The purpose of this study is to determine the impact of radiation exposure on lung cancer progression in vivo and assess the relevance of this knowledge to human carcinogenesis. K-ras(LA1) mice were irradiated with various doses and dose regimens and then monitored until death. Microarray analyses were performed using Illumina BeadChips on whole lung tissue 70 days after irradiation with a fractionated or acute dose of radiation and compared with age-matched unirradiated controls. Unique group classifiers were derived by comparative genomic analysis of three experimental cohorts. Survival analyses were performed using principal component analysis and k-means clustering on three lung adenocarcinoma, three breast adenocarcinoma, and two lung squamous carcinoma annotated microarray datasets. Radiation exposure accelerates lung cancer progression in the K-ras(LA1) lung cancer mouse model with dose fractionation being more permissive for cancer progression. A nonrandom inflammatory signature associated with this progression was elicited from whole lung tissue containing only benign lesions and predicts human lung and breast cancer patient survival across multiple datasets. Immunohistochemical analyses suggest that tumor cells drive predictive signature. These results demonstrate that radiation exposure can cooperate with benign lesions in a transgenic model of cancer by affecting inflammatory pathways, and that clinically relevant similarities exist between human lung and breast carcinogenesis. ©2014 AACR.

  2. Antioxidant vitamins and prevention of lung disease

    SciTech Connect

    Menzel, D.B. )

    1992-09-30

    Although the evidence for oxidative stress for air pollution in the human lung is fragmentary, the hypothesis that oxidative stress is an important, if not the sole, mechanism of toxicity of oxidizing air pollutants and tobacco smoke is compelling and growing. First, biochemical mechanisms have been worked out for oxidation of lung lipids by the gas phase of cigarette smoke, NO[sub 2] and O[sub 3]. The oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is more effective in preventing oxidation by NO[sub 2], and vitamin E is more effective against O[sub 3]. Second, multiple species of experimental animals develop lung disease similar to human bronchitis and emphysema from exposure to NO[sub 2] and O[sub 3], respectively. The development of these diseases occurs over a near lifetime exposure when the levels of NO[sub 2] or O[sub 3] are at near ambient air pollution values. Third, isolated human cells are protected against oxidative damage from NO[sub 2] and O[sub 3] by both vitamins C and E. Fourth, the vitamin C level in the lung either declines on exposure to NO[sub 2] for short-term exposures or increases on chronic cigarette smoke exposure. The effects of cigarette smoking on serum vitamin C is apparently complex and may be related to the daily intake of vitamin C as well as smoking. Serum vitamin C levels may be poor indicators of lung demands when daily vitamin C intakes are above 100 mg/day. Fifth, vitamin C supplementation protects against the effects of ambient levels of air pollution in adults as measured by histamine challenge. An augmented response to histamine challenge may represent increased lung permeability brought about by air pollution. In experimental animal and human experiments, the amount of vitamin C or E that afforded protection was in excess of the current recommended dietary allowance.

  3. Pediatric Lung Transplantation.

    PubMed

    Sweet, Stuart C

    2017-06-01

    Pediatric lung transplant is a viable option for treatment of end-stage lung disease in children, with > 100 pediatric lung transplants reported to the Registry of the International Society of Heart and Lung Transplantation each year. Long-term success is limited by availability of donor organs, debilitation as a result of chronic disease, impaired mucus clearance resulting from both surgical and pharmacologic interventions, increased risk for infection resulting from immunosuppression, and most importantly late complications, such as chronic lung allograft dysfunction. Opportunities for investigation and innovation remain in all of these domains: (1) Ex vivo lung perfusion is a promising technology with the potential for increasing the lung donor pool, (2) evolving extracorporeal support strategies coupled with effective rehabilitation will effectively bridge critically ill patients to transplant, and most importantly, (3) research efforts intended to increase our understanding of the underlying mechanisms of chronic lung allograft dysfunction will ultimately lead to the development of effective therapies to prevent or treat the variety of chronic lung allograft dysfunction presentations. Copyright © 2017 by Daedalus Enterprises.

  4. Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

    PubMed

    Mokra, D; Kosutova, P; Balentova, S; Adamkov, M; Mikolka, P; Mokry, J; Antosova, M; Calkovska, A

    2016-12-01

    Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and

  5. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation

    PubMed Central

    Basil, Maria C.; Levy, Bruce D.

    2017-01-01

    Specialized pro-resolving mediators (SPMs) are enzymatically derived from essential fatty acids and have important roles in orchestrating the resolution of tissue inflammation — that is, catabasis. Host responses to tissue infection elicit acute inflammation in an attempt to control invading pathogens. SPMs are lipid mediators that are part of a larger family of pro-resolving molecules, which includes proteins and gases, that together restrain inflammation and resolve the infection. These immunoresolvents are distinct from immunosuppressive molecules as they not only dampen inflammation but also promote host defence. Here, we focus primarily on SPMs and their roles in lung infection and inflammation to illustrate the potent actions these mediators play in restoring tissue homeostasis after an infection. PMID:26688348

  6. Your Lungs and Respiratory System

    MedlinePlus

    ... Lifesaver Kids Talk About: Coaches Your Lungs & Respiratory System KidsHealth > For Kids > Your Lungs & Respiratory System Print ... its regular size. You've just felt the power of your lungs! continue A Look Inside the ...

  7. 6 Common Cancers - Lung Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents ... for Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the ...

  8. Genetics Home Reference: lung cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions lung cancer lung cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Lung cancer is a disease in which certain cells ...

  9. Interstitial lung disease - adults - discharge

    MedlinePlus

    ... lung disease Pulmonary alveolar proteinosis Rheumatoid lung disease Sarcoidosis Patient Instructions Eating extra calories when sick - adults ... team. Related MedlinePlus Health Topics Interstitial Lung Diseases Sarcoidosis Browse the Encyclopedia A.D.A.M., Inc. ...

  10. Experimental studies on the effect of (Lambda-Cyhalothrin) insecticide on lungs and the ameliorating effect of plant extracts (Ginseng (Panax Ginseng) and garlic (Allium sativum L.) on asthma development in albino rats.

    PubMed

    Mohi El-Din, Mouchira M; Mostafa, Amna M; Abd-Elkader, Aml

    2014-04-16

    Lambda-cyhalothrin (LTC) is a synthetic pyrethroid insecticide for agricultural and public health applications. This study was to determine the pathological alterations of LTC in lungs, which has not previously been studied, and the ameliorating effects of plant extracts (ginseng and garlic) on the development of asthma in albino rats. Four groups (gps) of albino rats, (n = 20, average body weight = 200 gm with an age of 4 months), were formed. Gp 1 was kept as control. Gp 2 was injected intraperitoneally (i.p.) with LTC at a dose of 1/6 LD50 that is 9.34 mg/kg body weight (w.t.) daily for 21 days (d). Gp 3 & 4 were injected (i.p.) with ginseng at the dose of 200 mg/kg b.wt and garlic (Allium sativum L.) at the dose of 100 mg/kg b.wt., respectively, one hour before being given LTC at a dose of 1/6 LD50 (9.34 mg/kg b.wt.) daily. Each groups were divided into two sacrificed, at 15 and 21 d p.i. Blood and lung samples we