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Sample records for alveolar epithelial permeability

  1. Alveolar epithelial permeability in bronchial asthma in children

    International Nuclear Information System (INIS)

    Oishi, Takuji

    1993-01-01

    To evaluate alveolar epithelial permeability (k ep ) in children with bronchial asthma, 99m Tc-DTPA (diethylene triamine penta acetate) aerosol lung inhalation scintigraphies were performed. There was no correlation between the k ep value and the severity of asthma. On the other hand, out of 10 cases which had no aerosol deposition defect in the lung field, 4 showed high k ep values on the whole lung field and 7 had high k ep value areas, particularly apparent in the upper lung field. These results suggest that even when the central airway lesions are mild, severe damage exists in the alveolar region of the peripheral airway. (author)

  2. Clinical value of the alveolar epithelial permeability in various pulmonary diseases

    International Nuclear Information System (INIS)

    Todisco, T.; Dottorini, M.; Rossi, F.; Polidori, A.; Bruni, B.; Iannacci, L.; Palumbo, R.; Fedeli, L.

    1984-01-01

    The authors have measured the pulmonary epithelial permeability in normals, smokers, ex-smokers and in various pulmonary diseases, using the sup(99m)Tc-DTPA monodisperse radioaerosol delivered by a newly designed nebulizer. Reference values for alveolar epithelial permeability were those of their own laboratory. Accelerated clearance of small idrophylic solutes from the lungs to the blood was found in smokers and in all the patients with idiopathic diffuse pulmonary fibrosis, chronic obstructive lung disease, congestive heart failure, acute viral pneumonia and adult respiratory distress syndrome. The greatest increase of alveolar epithelial clearance was found in the lung zone affected by the viral infection. The normal upper-lover lobe gradient of epithelial clearance was lost only in some patients. The increased permeability of the alveolar wall, although not specific, is characteristic and early feature of many acute and chronic pulmonary disease. For practical purposes, this parameter, rather than diagnostic, should be considered as a sensitive index of alveolar damage and repair, especially suitable for the follow-up of patients with spontaneous or therapeutic reversibility of parenchimal lung diseases. (orig.)

  3. The influence of volatile anesthetics on alveolar epithelial permeability measured by noninvasive radionuclide lung scan

    International Nuclear Information System (INIS)

    Hung, Chih-Jen; Wu, Rick Sai-Chuen; Lin, Cheng-Chieh; Kao, Albert; Tsai, Jeffrey J.P.

    2003-01-01

    Many volatile anesthetics have long been thought to affect pulmonary functions including lung ventilation (LV) and alveolar epithelial permeability (AEP). The purpose of this study is to examine the influence of volatile anesthetics on LV and AEP by noninvasive radionuclide lung imaging of technetium-99m labeled diethylene triamine pentaacetic acid radioaerosol inhalation lung scan (DTPA lung scan). Twenty patients undergoing surgery and receiving volatile anesthesia with 1% halothane were enrolled as the study group 1. The other 20 patients undergoing surgery and receiving volatile anesthesia with 1.5% isoflurane were enrolled as the study group 2. At the same time, 20 patients undergoing surgery with intravenous anesthesia drugs were included as a control group. Before surgery, 1 hour after surgery, and 1 week after surgery, we investigated the 3 groups of patients with DTPA lung scan to evaluate LV and AEP by 99m Tc DTPA clearance halftime (T1/2). No significant change or abnormality of LV before surgery, 1 hour after surgery, or 1 week after surgery was found among the 3 groups of patients. In the control group, the 99m Tc DTPA clearance T1/2 was 63.5±16.4, 63.1±18.4, and 62.8±17.0 minutes, before surgery, 1 hour after surgery, and 1 week after surgery, respectively. In group 1, it was 65.9±9.3, 62.5±9.1, and 65.8±10.3 minutes, respectively. No significant change in AEP before surgery, 1 hour after surgery, or 1 week after surgery was found. However, in group 2, the 99m Tc DTPA clearance T1/2 was 65.5±13.2, 44.9±10.5, and 66.1±14.0 minutes, respectively. A significant transient change in AEP was found 1 hour after surgery, but it recovered 1 week after surgery. We conclude that volatile anesthesia is safe for LV and AEP, and only isoflurane can induce transient change of AEP. (author)

  4. Influence of hilar deposition in the evaluation of the alveolar epithelial permeability on 99mTc-DTPA aerosol inhaled scintigraphy

    International Nuclear Information System (INIS)

    Ogi, Shigeyuki; Uchiyama, Mayuki; Fukuda, Kunihiko; Urashima, Mitsuyoshi; Gotoh, Eisuke; Fukumitsu, Nobuyoshi

    2009-01-01

    We investigated whether hilar radioaerosol deposition affects the clearance rate of technetium-99m-labeled diethylenetriaminepentaacetic acid ( 99m Tc-DTPA) from peripheral alveolar regions. A total of 38 patients underwent 99m Tc-DTPA inhalation lung scintigraphy. Six region of interest (ROI) patterns were adopted: ROI 1 was outlined around the entire hemithorax, and ROIs 2-6 were outlined around the hemithorax but excluded square ROIs of different size in the hilar region. Half-times (T 1/2 ) were calculated with time-activity curves using one-compartment and two-compartment analyses. The T 1/2 of ROIs 1-5 were plotted against the T 1/2 of ROI 6, and regression lines were obtained with the least-squares method. The absolute values of the differences between surveyed values and regression line were calculated. The Wilcoxon test for trend and a single linear regression model were used to determine statistical significance. There were significant reductions in the absolute values of the differences between surveyed values and regression line from ROIs 1-5 by one-component analysis and the fast component of two-compartment analysis (P 99m Tc-DTPA from the alveoli in damaged lungs. The hilar region should be excluded from ROIs when alveolar epithelial permeability is evaluated. (author)

  5. Acute cigarette smoke exposure increases alveolar permeability in rabbits

    International Nuclear Information System (INIS)

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Roseberry, H.; Stevenson, J.L.; Clayton, J.

    1985-01-01

    The authors measured lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA) as an index of alveolar epithelial permeability in rabbits exposed to cigarette smoke. Eighteen rabbits were randomly assigned to 3 equal-size groups: control, all smoke exposure (ASE), and limited smoke exposure (LSE). Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 20-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biologic half-life (T 1 / 2 ). Mean T 1 / 2 minimum was significantly lower for ASE and LSE rabbits than by control rabbits. They observed a significant difference at 20 and 30 breath exposures between the control and ASE group mean values for T 1 / 2 , arterial blood pressure, and peak airway pressure. A combination of light and electron microscopy showed focal alveolar edema and hemorrhage in the ASE and LSE groups but no alveolar-capillary membrane damage. In summary, acute cigarette smoke exposure increases alveolar permeability as measured by /sup 99m/TcDTPA clearance, but there was no detectable ultrastructural alteration of the alveolar-capillary membrane

  6. Measurement of Regional and Global Pulmonary Clearance of 99mTc-DTPA (Demethylamitriptylene-Acetate): An Index of Alveolar Epithelial Permeability

    International Nuclear Information System (INIS)

    Vaskova, Olivija

    1996-01-01

    The main purpose of this study has been introduction of a new method for alveoli-capillary permeability evaluation. Many reports pointed out to the altered transit of soluble particles through this barrier. From pathophysiological aspect the main interest is the elucidation of permeability's alteration in different pulmonary pathology. We decided to use for lung epithelial permeability measurements 99m Tc-DTPA inhaled aerosols and sequential assessment of its lung clearance. The aerosols were obtained using oxygen flow nebulizers with aerosols' generators Ultra Vent (Malinkrodt) and Venticis II (CIS bio international) that enabled as to get submicron particles. Oxygen flow between 9 and 11 liters per minute was used. Optimum images were obtained with 1480 MBq of inhaled aerosols at least 2 to 3 minutes. DTPA that was used for aerosols labeling had been produced in our Department and the results were compared with DTPA provided by CIS bio international. High correlation between both agents was proven. During the whole study ex tamper prepared radiopharmaceuticals were used and quality control was done using paper chromatography method. Acquisition was done in sitting position with gamma camera interfaced to a ADAC and Scintiview. The measurements lasted for 20 minutes. Data were stored on 64x64 matrices. Regions of interest over both lungs were drown and each one was divided in three segments: apical, medial, and basal. Using computer program curves of 99m Tc-DTPA lung clearance were derived. From the obtained time activity curves half-time of the global and the regional lung clearance was assessed. In the control group comprised of 32 healthy volunteers (non-smokers) we had got values, used after works as reference range. Our normal values for global clearance are: 68±5,5 min. for left whole lung, 68,1±6,5 min for right whole lung, and 49±7,7 min for apical, 66,9±8 min for middle, and 75,9±6,4 min basal regional lung clearance, and they are in keeping with the

  7. Modulation of epithelial sodium channel in human alveolar epithelial ...

    African Journals Online (AJOL)

    Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway. Bi-Huan Cheng1,2, Li-Wei Pan2, Sheng-Rong Zhang3, Bin-Yu Ying2, Ben-Ji. Wang2, Guo-Liang Lin2 and Shi-Fang Ding1*. 1Department of Critical Care Medicine, Qilu Hospital of Shandong ...

  8. Inflammasome Inhibition Suppresses Alveolar Cell Permeability Through Retention of Neuregulin-1 (NRG-1

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    Rajanbabu Venugopal

    2015-07-01

    Full Text Available Background: Neuregulin (NRG-1-human epidermal receptor (HER-2 signaling pathway is a key regulator of IL-1β-mediated pulmonary inflammation and epithelial permeability. The inflammasome is a newly discovered molecular platform required for caspase-1 activation and maturation of IL-1β. However, the role of the inflammasome in NRG-1-HER2 signaling-mediated alveolar cell permeability is unknown. Methods: The inflammasome was activated or inhibited in THP-1 cells; supernatants from these cells were added to A549 cells and human small airway epithelial cells (HSAEC. The protein expression of NRG-1 and phospho-HER2 (pHER2 were measured by Western blot analysis and epithelial permeability was measured using Lucifer yellow dye. Results: Results reveal that alveolar permeability in A549 cells and HSAEC is increased when treated with supernatants of inflammasome-activated THP-1 cells. Alveolar permeability is significantly suppressed when treated with supernatant of inflammasome-inhibited THP-1 cells. Inflammasome-mediated permeability is decreased when A549 cells and HSAEC are pretreated with IL-1β receptor antagonist (IL-1βRA. In addition, HER2 kinase inhibitor AG825 or NRG-1 inhibitor TAPI inhibits inflammasome-mediated permeability in A549 cells and HSAEC demonstrating critical roles of IL-1β, NRG-1, and HER2 in inflammasome-mediated alveolar permeability. Conclusion: These findings suggest that inflammasome-induced alveolar cell permeability is mediated by NRG-1/HER2 signaling through IL-1β regulation.

  9. Haemophilia, AIDS and lung epithelial permeability

    Energy Technology Data Exchange (ETDEWEB)

    O' Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G. (Haemophilia Centre and Coagulation Research Unit, Department of Nuclear Medicine, Rayne Institute, St. Thomas' Hospital, London (United Kingdom))

    1990-01-01

    Lung {sup 99m}Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung {sup 99m}Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of {sup 99m}Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au).

  10. Haemophilia, AIDS and lung epithelial permeability

    International Nuclear Information System (INIS)

    O'Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G.

    1990-01-01

    Lung 99m Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung 99m Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of 99m Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au)

  11. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

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    Jacob Barbara A

    2009-02-01

    Full Text Available Abstract Background HIV-infected individuals are at increased risk for acute and chronic airway disease even though there is no evidence that the virus can infect the lung epithelium. Although HIV-related proteins including gp120 and Tat can directly cause oxidant stress and cellular dysfunction, their effects in the lung are unknown. The goal of this study was to determine the effects of HIV-1 transgene expression in rats on alveolar epithelial barrier function. Alveolar epithelial barrier function was assessed by determining lung liquid clearance in vivo and alveolar epithelial monolayer permeability in vitro. Oxidant stress in the alveolar space was determined by measuring the glutathione redox couple by high performance liquid chromatography, and the expression and membrane localization of key tight junction proteins were assessed. Finally, the direct effects of the HIV-related proteins gp120 and Tat on alveolar epithelial barrier formation and tight junction protein expression were determined. Results HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization. Conclusion Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.

  12. NO2 decreases paracellular resistance to ion and solute flow in alveolar epithelial monolayers

    International Nuclear Information System (INIS)

    Cheek, J.M.; Kim, K.J.; Crandall, E.D.

    1990-01-01

    Primary cultured monolayers of rat alveolar epithelial cells grown on tissue culture-treated Nuclepore filters were exposed to 2.5 ppm nitrogen dioxide NO 2 for 2-20 min. Changes in monolayer bioelectric properties and solute permeabilities were subsequently measured. Exposure to NO 2 produced a dose-dependent decrease in monolayer transepithelial electrical resistance (Rt), whereas monolayer short-circuit current was unaffected. Post-exposure monolayer permeability to 14 C-sucrose (which primarily crosses alveolar epithelium via the paracellular pathway) increased markedly. That for 3 H-glycerol (which permeates through both paracellular and transcellular pathways) increased to a lesser extent. Partial recovery of Rt and solute permeabilities was noted by 48-h post-exposure. The time courses of the decrease in Rt and increase in solute permeabilities were similar. These results suggest that NO 2 primarily impairs passive alveolar epithelial barrier functions in vitro, probably by altering intercellular junctions, and does not appear to directly affect cell membrane active ion transport processes. When correlated with results obtained from experimental approaches, studies of in vitro alveolar epithelial monolayers may facilitate investigations of dosimetry, sites, and mechanisms of oxidant injury in the lung

  13. Cultured alveolar epithelial cells from septic rats mimic in vivo septic lung.

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    Taylor S Cohen

    2010-06-01

    Full Text Available Sepsis results in the formation of pulmonary edema by increasing in epithelial permeability. Therefore we hypothesized that alveolar epithelial cells isolated from septic animals develop tight junctions with different protein composition and reduced barrier function relative to alveolar epithelial cells from healthy animals. Male rats (200-300 g were sacrificed 24 hours after cecal ligation and double puncture (2CLP or sham surgery. Alveolar epithelial cells were isolated and plated on fibronectin-coated flexible membranes or permeable, non-flexible transwell substrates. After a 5 day culture period, cells were either lysed for western analysis of tight junction protein expressin (claudin 3, 4, 5, 7, 8, and 18, occludin, ZO-1, and JAM-A and MAPk (JNK, ERK, an p38 signaling activation, or barrier function was examined by measuring transepithelial resistance (TER or the flux of two molecular tracers (5 and 20 A. Inhibitors of JNK (SP600125, 20 microM and ERK (U0126, 10 microM were used to determine the role of these pathways in sepsis induced epithelial barrier dysfunction. Expression of claudin 4, claudin 18, and occludin was significantly lower, and activation of JNK and ERK signaling pathways was significantly increased in 2CLP monolayers, relative to sham monolayers. Transepithelial resistance of the 2CLP monolayers was reduced significantly compared to sham (769 and 1234 ohm-cm(2, respectively, however no significant difference in the flux of either tracer was observed. Inhibition of ERK, not JNK, significantly increased TER and expression of claudin 4 in 2CLP monolayers, and prevented significant differences in claudin 18 expression between 2CLP and sham monolayers. We conclude that alveolar epithelial cells isolated from septic animals form confluent monolayers with impaired barrier function compared to healthy monolayers, and inhibition of ERK signaling partially reverses differences between these monolayers. This model provides a unique

  14. Modeling Alveolar Epithelial Cell Behavior In Spatially Designed Hydrogel Microenvironments

    Science.gov (United States)

    Lewis, Katherine Jean Reeder

    The alveolar epithelium consists of two cell phenotypes, elongated alveolar type I cells (AT1) and rounded alveolar type II cells (ATII), and exists in a complex three-dimensional environment as a polarized cell layer attached to a thin basement membrane and enclosing a roughly spherical lumen. Closely surrounding the alveolar cysts are capillary endothelial cells as well as interstitial pulmonary fibroblasts. Many factors are thought to influence alveolar epithelial cell differentiation during lung development and wound repair, including physical and biochemical signals from the extracellular matrix (ECM), and paracrine signals from the surrounding mesenchyme. In particular, disrupted signaling between the alveolar epithelium and local fibroblasts has been implicated in the progression of several pulmonary diseases. However, given the complexity of alveolar tissue architecture and the multitude of signaling pathways involved, designing appropriate experimental platforms for this biological system has been difficult. In order to isolate key factors regulating cellular behavior, the researcher ideally should have control over biophysical properties of the ECM, as well as the ability to organize multiple cell types within the scaffold. This thesis aimed to develop a 3D synthetic hydrogel platform to control alveolar epithelial cyst formation, which could then be used to explore how extracellular cues influence cell behavior in a tissue-relevant cellular arrangement. To accomplish this, a poly(ethylene glycol) (PEG) hydrogel network containing enzymatically-degradable crosslinks and bioadhesive pendant peptides was employed as a base material for encapsulating primary alveolar epithelial cells. First, an array of microwells of various cross-sectional shapes was photopatterned into a PEG gel containing photo-labile crosslinks, and primary ATII cells were seeded into the wells to examine the role of geometric confinement on differentiation and multicellular arrangement

  15. Imaging alveolar-capillary permeability in experimental respiratory distress syndrome

    International Nuclear Information System (INIS)

    Suzuki, T.; Watanabe, S.; Wagner, H.N.; Swift, D.L.; Proctor, D.F.

    1982-01-01

    Pulmonary edema can be induced in dogs by low doses of oleic acid (20 μl/kg) given intravenously, simulating the adult respiratory distress syndrome (ARDS). Alveolar-capillary permeability was measured in dogs, using sup(99m)Tc-DTPA and sup(99m)Tc-albumin fine aerosols produced by a newly designed separator. This separator eliminates the effect of mucociliary movement on aerosol clearance. The small molecular-laden aerosol particles were cleared in the order: sup(99m)-TcO 4 - , sup(99m)Tc-DTPA, and sup(99m)Tc-disofenin; the Tsub(1/2) of lung clearance correlated with molecular sizes. Experimental ARDS increased the lung clearance of sup(99m)Tc-DTPA. Lung clearance of large molecule (sup(99m)Tc-albumin) laden aerosol particles was not accelerated in the ARDS model. Inhalation with fine aerosols revealed increased alveolar permeability in the ARDS model without any change of cardiac output

  16. Dynamic /sup 99m/Tc-DTPA radioaerosol lung scanning for the evaluation of alveolar-capillary barrier permeability

    Energy Technology Data Exchange (ETDEWEB)

    Maini, C L; Marchetti, L; Bonetti, M G; Giordano, A; Pistelli, R; Antonelli Incalzi, R

    1987-01-01

    Pulmonary clearance of small droplet /sup 99m/Tc-DTPA radioaerosol was studied in 100 patients (12 normal subjects, N; 10 asymptomatic healthy smoker, FA; 31 patients with interstitial lung diseases, IP; 47 patients with chronic obstructive lung disease, BPCO). The first seven minutes of clearance were described with the function At=Ao*exp(-K*t) and the time constant K was considered representative of the /sup 99m/Tc-DTPA clearance rate and hence of the alveolar-capillary barrier permeability. Groups FA, IP and BPCO showed a significant (p<0.05) or a highly significant (p<0.01) increase in permeability when compared to group N. No correlation was found between permeability and bronchial obstraction tests. The following conclusions were drawn: 1) /sup 99m/Tc-DTPA dynamic lung scanning is an easy, non-invasive method to assess derangements of alveolar-capillary barrier permeability secondary to epithelial damage; 2) permeability increase is a very early effect of cigarette smoke damafe to the epithelium; 3) other mechanisms of epithelial injury are present in diffuse lung disease; 4) while the clinical role of this new pathophysiological test is not yet clear, it is likely that it may become a very early marker of pulmonary epithelial damage in diffuse lung disease. 35 refs.

  17. Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

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    Araki Hiromasa

    2007-04-01

    Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

  18. Ontogeny of pulmonary alveolar epithelial markers of differentiation.

    Science.gov (United States)

    Joyce-Brady, M F; Brody, J S

    1990-02-01

    We studied differentiation of the pulmonary epithelium in the periphery of fetal rat lung in vivo and in vitro by comparing the ontogeny of cell-surface glycoconjugates with that of surfactant phospholipids. Apical surface binding of the lectin Maclura pomifera agglutinin (MPA) and expression of a 200-kDa MPA-binding glycoprotein (MPA-gp200) was evident at 20 days gestation in type 2 cells, but did not correlate with ultrastructural features of type 2 cell differentiation. Epithelial cells isolated from peripheral lung of 18-day gestation fetal rats displayed hormone-sensitive surfactant synthesis prior to the hormone-insensitive expression of MPA-gp200. Expression of MPA-gp200 occurred in association with the appearance of many new apical surface proteins suggesting a hormone-independent process of polar membrane differentiation. Thus membrane and secretory differentiation are discordant and can be dissociated. In vivo binding of Ricinus communis 1 agglutinin (RCA1), an apical marker of the differentiated alveolar type 1 cell occurred in undifferentiated peripheral lung epithelial cells as early as 18 days gestation, disappeared from differentiating type 2 cells and appeared in differentiated type 1 cells. Both undifferentiated fetal epithelial cells at 18 days gestation and fully differentiated type 1 cells express multiple glycoproteins with terminal beta-linked galactose residues which bind RCA1. Some of these RCA1-binding glycoproteins appear to be similar. These observations suggest that alveolar epithelial type 1 cells may derive directly from undifferentiated peripheral lung epithelial cells as well as from fully differentiated type 2 cells. In addition, terminal differentiation of fetal lung peripheral epithelium into type 1 and type 2 cells may involve repression as well as induction of differentiation-related genes.

  19. Dynamic 99mTc-DTPA radioaerosol lung scanning for the evaluation of alveolar-capillary barrier permeability

    International Nuclear Information System (INIS)

    Maini, C.L.; Marchetti, L.; Bonetti, M.G.; Giordano, A.; Pistelli, R.; Antonelli Incalzi, R.

    1987-01-01

    Pulmonary clearance of small droplet 99m Tc-DTPA radioaerosol was studied in 100 patients (12 normal subjects, N; 10 asymptomatic healthy smoker, FA; 31 patients with interstitial lung diseases, IP; 47 patients with chronic obstructive lung disease, BPCO). The first seven minutes of clearance were described with the function At=Ao*exp(-K*t) and the time constant K was considered representative of the 99m Tc-DTPA clearance rate and hence of the alveolar-capillary barrier permeability. Groups FA, IP and BPCO showed a significant (p 99m Tc-DTPA dynamic lung scanning is an easy, non-invasive method to assess derangements of alveolar-capillary barrier permeability secondary to epithelial damage; 2) permeability increase is a very early effect of cigarette smoke damafe to the epithelium; 3) other mechanisms of epithelial injury are present in diffuse lung disease; 4) while the clinical role of this new pathophysiological test is not yet clear, it is likely that it may become a very early marker of pulmonary epithelial damage in diffuse lung disease

  20. Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS.

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    Wenli Yang

    Full Text Available The hepatopulmonary syndrome (HPS develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2 play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL. We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064 induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.

  1. Simulation of lung alveolar epithelial wound healing in vitro.

    Science.gov (United States)

    Kim, Sean H J; Matthay, Michael A; Mostov, Keith; Hunt, C Anthony

    2010-08-06

    The mechanisms that enable and regulate alveolar type II (AT II) epithelial cell wound healing in vitro and in vivo remain largely unknown and need further elucidation. We used an in silico AT II cell-mimetic analogue to explore and better understand plausible wound healing mechanisms for two conditions: cyst repair in three-dimensional cultures and monolayer wound healing. Starting with the analogue that validated for key features of AT II cystogenesis in vitro, we devised an additional cell rearrangement action enabling cyst repair. Monolayer repair was enabled by providing 'cells' a control mechanism to switch automatically to a repair mode in the presence of a distress signal. In cyst wound simulations, the revised analogue closed wounds by adhering to essentially the same axioms available for alveolar-like cystogenesis. In silico cell proliferation was not needed. The analogue recovered within a few simulation cycles but required a longer recovery time for larger or multiple wounds. In simulated monolayer wound repair, diffusive factor-mediated 'cell' migration led to repair patterns comparable to those of in vitro cultures exposed to different growth factors. Simulations predicted directional cell locomotion to be critical for successful in vitro wound repair. We anticipate that with further use and refinement, the methods used will develop as a rigorous, extensible means of unravelling mechanisms of lung alveolar repair and regeneration.

  2. Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis.

    OpenAIRE

    Eklund, A; Blaschke, E

    1986-01-01

    The effect of altered alveolar-capillary permeability on angiotensin converting enzyme (ACE) activity in serum (SACE) was studied in 45 patients with sarcoidosis and 21 healthy controls. In sarcoidosis increased albumin concentrations in the bronchoalveolar lavage fluid (L albumin) and increased ratios of L albumin to albumin in serum (S albumin) indicated an increased permeability of the alveolar-capillary membrane. ACE activity in the lavage fluid (LACE) was correlated with the number of al...

  3. Detection of alveolar epithelial injury by 99mTc-DTPA radioaerosol inhalation lung scan following blunt chest trauma

    International Nuclear Information System (INIS)

    Okudan, B.; Han, S.; Baldemir, M.; Yildiz, M.

    2004-01-01

    DTPA clearance rate is a reliable index of alveolar epithelial permeability, and is a highly sensitive marker of pulmonary epithelial damage, even of mild degree. In this study, 99m Tc-DTPA aerosol inhalation scintigraphy was used to assess the pulmonary epithelial membrane permeability and to investigate the possible application of this permeability value as an indicator of early alveolar or interstitial changes in patients with blunt chest trauma. A total of 26 patients was chest trauma (4 female, 22 male, 31-80 yrs, mean age; 53±13 yrs) who were referred to the emergency department in our hospital participated in this study. Technetium-99m diethylene triamine pentaacetic acid (DTPA) aerosol inhalation scintigraphy was performed on the first and thirtieth days after trauma. Clearance half times (T 1/2 ) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. On the first day, mean T 1/2 value of the whole lung was 63±19 minutes (min), and thirtieth day mean T 1/2 value was 67±21 min. On the first day, mean PI values of the lung and 30th day mean PI value were 0.60±0.05, and 0.63 ±0.05, respectively. Significant changes were observed in radioaerosol clearance and penetration indices. Following chest trauma, clearance of 99m Tc-DTPA increased owing to breakdown of the alveolar-capillary barrier. This increase in the epithelial permeability of the lung appears to be an early manifestation of lung disease that may lead to efficient therapy in the early phase. (author)

  4. Clinical studies of alveolar-capillary permeability using technetium-99m DTPA aerosol

    International Nuclear Information System (INIS)

    Sundram, F.X.

    1995-01-01

    Soluble radioaerosols such as technetium-99m diethylene triamine pentacetate (DTPA) permit simple quantitative studies of alveolar-capillary permeability to be performed, since the submicronic aerosols are deposited mainly at the lung periphery and are cleared across the alveolar-capillary membrane. Regional alterations in permeability can also be noted using this radionuclide technique. We have measured the pulmonary epithelial permeability in normal subjects and the alteration in smokers, glue-sniffers, patients with inhalation burns, chronic obstructive pulmonary disease (COPD) and patients with lung metastases from thyroid cancer treated with radioiodine 131 I. In the normal volunteers, the time taken for 50% of inhaled 99m Tc DTPA to be cleared from the lungs (T1/2) was 66 minutes±1 sd of 12 mins. The smokers had a mean T1/2 of 20 mins±1 sd 4 min. In the hard-core glue-sniffing group, the majority were smokers who had stopped smoking and glue-sniffing for periods varying from 1 day to 42 days, and it was possible to note the changes in clearance times against period of abstinence. In the patients with inhalation burns, there was change in lung clearance arising from pulmonary epithelial damage; these patients showed increased rate of clearance (short T1/2) with mean T1/2 of 36 min±1 sd of 11 mins, while the retention images revealed regional lung damage in moderately severe inhalation burns. Twenty-four patients with COPD had inhalation scans done with Tc-99m tin colloid radioaerosol, and these images were compared with the perfusion lung scans done with 99m Tc macroaggregated albumin (MAA); in general the perfusion images matched the defects noted in the inhalation scans. The 99m Tc DTPA clearance rate in these patients was normal i.e. T1/2=78±14 mins. In the thyroid cancer patients with lung metastases, who had high doses of radioiodine treatment, the T1/2 values were normal or prolonged slightly, mean T1/2=76 min±23. (author)

  5. Alveolocapillary model system to study alveolar re-epithelialization

    Energy Technology Data Exchange (ETDEWEB)

    Willems, Coen H.M.P.; Zimmermann, Luc J.I.; Sanders, Patricia J.L.T.; Wagendorp, Margot; Kloosterboer, Nico [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands); Cohen Tervaert, Jan Willem [Division of Clinical and Experimental Immunology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht (Netherlands); Duimel, Hans J.Q.; Verheyen, Fons K.C.P. [Electron Microscopy Unit, Department of Molecular Cell Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Iwaarden, J. Freek van, E-mail: f.vaniwaarden@maastrichtuniversity.nl [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands)

    2013-01-01

    In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively. These fluorescent proteins allowed the real time assessment of the integrity of the monolayers and the automated analysis of the wound healing process after a scratch injury. The HPMECs significantly attenuated the speed of re-epithelialization, which was associated with the proximity to the A549 layer. Examination of cross-sectional transmission electron micrographs of the model system revealed protrusions through the membrane pores and close contact between the A549 cells and the HPMECs. Immunohistochemical analysis showed that these close contacts consisted of heterocellular gap-, tight- and adherens-junctions. Additional analysis, using a fluorescent probe to assess gap-junctional communication, revealed that the HPMECs and A549 cells were able to exchange the fluorophore, which could be abrogated by disrupting the gap junctions using connexin mimetic peptides. These data suggest that the pulmonary microvascular endothelium may impact the re-epithelialization process. -- Highlights: ► Model system for vital imaging and high throughput screening. ► Microvascular endothelium influences re-epithelialization. ► A549 cells form protrusions through membrane to contact HPMEC. ► A549 cells and HPMECs form heterocellular tight-, gap- and adherens-junctions.

  6. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation.

    Science.gov (United States)

    Ware, L B; Golden, J A; Finkbeiner, W E; Matthay, M A

    1999-03-01

    Reperfusion lung injury is an important cause of morbidity and mortality after orthotopic lung transplantation. The purpose of this study was to investigate the function of the alveolar epithelium in the setting of reperfusion lung injury. Simultaneous samples of pulmonary edema fluid and plasma were collected from eight patients with severe post-transplantation reperfusion edema. The edema fluid to plasma protein ratio was measured, an indicator of alveolar-capillary barrier permeability. The initial edema fluid to plasma protein ratio was > 0.75 in six of eight patients, confirming the presence of increased permeability of the alveolar-capillary barrier. Graft ischemic time was positively correlated with the degree of permeability (r = 0.77, p mean +/- SD). Alveolar fluid clearance was calculated from serial samples in six patients. Intact alveolar fluid clearance correlated with less histologic injury, rapid resolution of hypoxemia, and more rapid resolution of radiographic infiltrates. The two patients with no net alveolar fluid clearance had persistent hypoxemia and more severe histologic injury. This study provides the first direct evidence that increased permeability to protein is the usual cause of reperfusion edema after lung transplantation, with longer ischemic times associated with greater permeability to protein in the transplanted lung. The high rates of alveolar fluid clearance indicate that the fluid transport capacity of the alveolar epithelium may be well preserved in the allograft despite reperfusion lung injury. The ability to reabsorb fluid from the alveolar space was a marker of less severe reperfusion injury, whereas the degree of alveolar-capillary barrier permeability to protein was not. Measurement of alveolar fluid clearance may be useful to assess the severity of reperfusion lung injury and to predict outcome when pulmonary edema develops after lung transplantation.

  7. Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

    International Nuclear Information System (INIS)

    Gao, Rundi; Chen, Ruilin; Cao, Yu; Wang, Yuan; Song, Kang; Zhang, Ya; Yang, Junchao

    2017-01-01

    Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

  8. Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Rundi; Chen, Ruilin; Cao, Yu [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Wang, Yuan [Department of Pulmonary Function, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Song, Kang [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Zhang, Ya [Zhejiang Chinese Medicine University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang Province 310006 (China); Yang, Junchao, E-mail: yangjunchaozj@zcmu.edu.cn [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China)

    2017-03-01

    Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

  9. Lung epithelial permeability and inhaled furosemide. Added dimensions in asthmatics

    International Nuclear Information System (INIS)

    Bhure, U.N.; Bhure, S.U.; Bhatt, B.M.; Mistry, S.; Pednekar, S.J.; Chari, V.V.; Desai, S.A.; Joshi, J.M.; Paidhungat, A.J.

    2009-01-01

    Lung clearance rates of inhaled 99m Tc-diethylene-triamine-pentaacetic acid (DTPA) aerosols constitute a sensitive index to evaluate the permeability changes characteristic of airway epithelial damage. It was thought that edema of the airway wall which is reported in asthma could be relieved with a diuretic like furosemide, helping to relieve the symptoms. We intended to study the effect of inhaled furosemide on lung epithelial permeability in asthmatics and smokers with the help of 99m Tc-DTPA lung clearance test (LCT). The study included three groups (n=15), viz. normal healthy controls, asymptomatic chronic smokers, and chronic persistent asthmatics. Each subject underwent the LCT twice, baseline and post-furosemide (Lasix) study, within a week's interval. The post-furosemide study was carried out 15 min after inhalation of 10 mg of lasix. Lung epithelial permeability was determined in terms of clearance half-life (T 1/2 ). The baseline mean T 1/2 values for controls, smokers, and asthmatics were 50.95±16.58, 20.81±5.47, 24.06±6.19 min, respectively. Post-lasix T 1/2 values were 50.83±15.84, 20.70±5.65, 41.27±15.07 min, respectively. There was a significant difference (P<0.001) in baseline and post-lasix clearance values in asthmatics only. Baseline lung epithelial permeability was altered in smokers and asthmatics compared to the controls. Furosemide was effective only in asthmatics in reverting the permeability almost back to the normal range. Inhaled furosemide was effective even in moderate and severe asthmatics. Furosemide has multiple mechanisms of action. It possibly acts at bronchial level in view of the pathology in asthmatics lying in the airways. (author)

  10. The Milieu of Damaged Alveolar Epithelial Type 2 Cells Stimulates Alveolar Wound Repair by Endogenous and Exogenous Progenitors

    Science.gov (United States)

    Buckley, Susan; Shi, Wei; Carraro, Gianni; Sedrakyan, Sargis; Da Sacco, Stefano; Driscoll, Barbara A.; Perin, Laura; De Filippo, Roger E.

    2011-01-01

    Alveolar epithelial integrity is dependent upon the alveolar milieu, yet the milieu of the damaged alveolar epithelial cell type 2 (AEC2) has been little studied. Characterization of its components may offer the potential for ex vivo manipulation of stem cells to optimize their therapeutic potential. We examined the cytokine profile of AEC2 damage milieu, hypothesizing that it would promote endogenous epithelial repair while recruiting cells from other locations and instructing their engraftment and differentiation. Bronchoalveolar lavage and lung extract from hyperoxic rats represented AEC2 in vivo damage milieu, and medium from a scratch-damaged AEC2 monolayer represented in vitro damage. CINC-2 and ICAM, the major cytokines detected by proteomic cytokine array in AEC2 damage milieu, were chemoattractive to normoxic AECs and expedited in vitro wound healing, which was blocked by their respective neutralizing antibodies. The AEC2 damage milieu was also chemotactic for exogenous uncommitted human amniotic fluid stem cells (hAFSCs), increasing migration greater than 20-fold. hAFSCs attached within an in vitro AEC2 wound and expedited wound repair by contributing cytokines migration inhibitory factor and plasminogen activator inhibitor 1 to the AEC2 damage milieu, which promoted wound healing. The AEC2 damage milieu also promoted differentiation of a subpopulation of hAFSCs to express SPC, TTF-1, and ABCA3, phenotypic markers of distal alveolar epithelium. Thus, the microenvironment created by AEC2 damage not only promotes autocrine repair but also can attract uncommitted stem cells, which further augment healing through cytokine secretion and differentiation. PMID:21700959

  11. Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Marco Checa

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive and lethal disease of unknown etiology. A growing body of evidence indicates that it may result from an aberrant activation of alveolar epithelium, which induces the expansion of the fibroblast population, their differentiation to myofibroblasts and the excessive accumulation of extracellular matrix. The mechanisms that activate the alveolar epithelium are unknown, but several studies indicate that smoking is the main environmental risk factor for the development of IPF. In this study we explored the effect of cigarette smoke on the gene expression profile and signaling pathways in alveolar epithelial cells. Lung epithelial cell line from human (A549, was exposed to cigarette smoke extract (CSE for 1, 3, and 5 weeks at 1, 5 and 10% and gene expression was evaluated by complete transcriptome microarrays. Signaling networks were analyzed with the Ingenuity Pathway Analysis software. At 5 weeks of exposure, alveolar epithelial cells acquired a fibroblast-like phenotype. At this time, gene expression profile revealed a significant increase of more than 1000 genes and deregulation of canonical signaling pathways such as TGF-β and Wnt. Several profibrotic genes involved in EMT were over-expressed, and incomplete EMT was observed in these cells, and corroborated in mouse (MLE-12 and rat (RLE-6TN epithelial cells. The secretion of activated TGF-β1 increased in cells exposed to cigarette smoke, which decreased when the integrin alpha v gene was silenced. These findings suggest that the exposure of alveolar epithelial cells to CSE induces the expression and release of a variety of profibrotic genes, and the activation of TGF-β1, which may explain at least partially, the increased risk of developing IPF in smokers.

  12. Glucose-6-phosphate dehydrogenase in rat lung alveolar epithelial cells. An ultrastructural enzyme-cytochemical study

    Directory of Open Access Journals (Sweden)

    S Matsubara

    2010-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism, and it plays an important role in cell proliferation and antioxidant regulation within cells in various organs. Although marked cell proliferation and oxidant/antioxidant metabolism occur in lung alveolar epithelial cells, definite data has been lacking as to whether cytochemically detectable G6PD is present in alveolar epithelial cells. The distribution pattern of G6PD within these cells, if it is present, is also unknown. The purpose of the present study was to investigate the subcellular localization of G6PD in alveolar cells in the rat lung using a newly- developed enzyme-cytochemistry (copper-ferrocyanide method. Type I cells and stromal endothelia and fibroblasts showed no activities. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of type II alveolar epithelial cells. The cytochemical controls ensured specific detection of enzyme activity. This enzyme may play a role in airway defense by delivering substances for cell proliferation and antioxidant forces, thus maintaining the airway architecture.

  13. Complementary roles of KCa3.1 channels and β1-integrin during alveolar epithelial repair.

    Science.gov (United States)

    Girault, Alban; Chebli, Jasmine; Privé, Anik; Trinh, Nguyen Thu Ngan; Maillé, Emilie; Grygorczyk, Ryszard; Brochiero, Emmanuelle

    2015-09-04

    Extensive alveolar epithelial injury and remodelling is a common feature of acute lung injury and acute respiratory distress syndrome (ARDS) and it has been established that epithelial regeneration, and secondary lung oedema resorption, is crucial for ARDS resolution. Much evidence indicates that K(+) channels are regulating epithelial repair processes; however, involvement of the KCa3.1 channels in alveolar repair has never been investigated before. Wound-healing assays demonstrated that the repair rates were increased in primary rat alveolar cell monolayers grown on a fibronectin matrix compared to non-coated supports, whereas an anti-β1-integrin antibody reduced it. KCa3.1 inhibition/silencing impaired the fibronectin-stimulated wound-healing rates, as well as cell migration and proliferation, but had no effect in the absence of coating. We then evaluated a putative relationship between KCa3.1 channel and the migratory machinery protein β1-integrin, which is activated by fibronectin. Co-immunoprecipitation and immunofluorescence experiments indicated a link between the two proteins and revealed their cellular co-distribution. In addition, we demonstrated that KCa3.1 channel and β1-integrin membrane expressions were increased on a fibronectin matrix. We also showed increased intracellular calcium concentrations as well as enhanced expression of TRPC4, a voltage-independent calcium channel belonging to the large TRP channel family, on a fibronectin matrix. Finally, wound-healing assays showed additive effects of KCa3.1 and TRPC4 inhibitors on alveolar epithelial repair. Taken together, our data demonstrate for the first time complementary roles of KCa3.1 and TRPC4 channels with extracellular matrix and β1-integrin in the regulation of alveolar repair processes.

  14. Transcriptomic profiling of primary alveolar epithelial cell differentiation in human and rat

    Directory of Open Access Journals (Sweden)

    Crystal N. Marconett

    2014-12-01

    Full Text Available Cell-type specific gene regulation is a key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how changes in transcriptional activation during alveolar epithelial cell (AEC differentiation determine phenotype. We performed transcriptomic profiling using in vitro differentiation of human and rat primary AEC. This model recapitulates in vitro an in vivo process in which AEC transition from alveolar type 2 (AT2 cells to alveolar type 1 (AT1 cells during normal maintenance and regeneration following lung injury. Here we describe in detail the quality control, preprocessing, and normalization of microarray data presented within the associated study (Marconett et al., 2013. We also include R code for reproducibility of the referenced data and easily accessible processed data tables.

  15. CXCL9 Regulates TGF-β1-Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells.

    Science.gov (United States)

    O'Beirne, Sarah L; Walsh, Sinead M; Fabre, Aurélie; Reviriego, Carlota; Worrell, Julie C; Counihan, Ian P; Lumsden, Robert V; Cramton-Barnes, Jennifer; Belperio, John A; Donnelly, Seamas C; Boylan, Denise; Marchal-Sommé, Joëlle; Kane, Rosemary; Keane, Michael P

    2015-09-15

    Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial marker thyroid transcription factor-1 and the mesenchymal marker α-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-β1 and CXCL9, with Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-β1-induced EMT. A decrease in TGF-β1-induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-β1-induced EMT. Copyright © 2015 by The American Association of Immunologists, Inc.

  16. Changes in permeability of the alveolar-capillary barrier in firefighters.

    Science.gov (United States)

    Minty, B D; Royston, D; Jones, J G; Smith, D J; Searing, C S; Beeley, M

    1985-09-01

    The effect on alveolar-capillary barrier permeability of chronic exposure to a smoke produced by the partial combusion of diesel oil, paraffin, and wood was examined. An index of permeability was determined from the rate of transfer from the lung into the blood of the hydrophilic, labelled chelate 99mTc diethylene triamine penta-acetate (MW 492 dalton). The results of this test were expressed as the half time clearance of the tracer from the lung into the blood (T1/2 LB). The study was carried out at the Royal Naval Firefighting School, HMS Excellent. Permeability index was measured on seven non-smoking naval firefighting instructors who had worked at the school for periods of longer than two and a half months. Tests of airway function and carbon monoxide transfer factor were performed on four of these seven instructors. The results of the permeability index showed a T1/2 LB of 26 min +/- 5 (SEM) which differed significantly from that of normal non-smokers. By contrast all other lung function tests had values within the predicted normal range.

  17. Dexmedetomidine Attenuates Oxidative Stress Induced Lung Alveolar Epithelial Cell Apoptosis In Vitro

    Directory of Open Access Journals (Sweden)

    Jian Cui

    2015-01-01

    Full Text Available Background. Oxidative stress plays a pivotal role in the lung injuries of critical ill patients. This study investigates the protection conferred by α2 adrenoceptor agonist dexmedetomidine (Dex from lung alveolar epithelial cell injury induced by hydrogen peroxide (H2O2 and the underlying mechanisms. Methods. The lung alveolar epithelial cell line, A549, was cultured and then treated with 500 μM H2O2 with or without Dex (1 nM or Dex in combination with atipamezole (10 nM, an antagonist of α2 receptors. Their effect on mitochondrial membrane potential (Δψm, reactive oxygen species (ROS, and the cell cycle was assessed by flow cytometry. Cleaved-caspases 3 and 9, BAX, Bcl-2, phospho-mTOR (p-mTOR, ERK1/2, and E-cadherin expression were also determined with immunocytochemistry. Results. Upregulation of cleaved-caspases 3 and 9 and BAX and downregulation of Bcl-2, p-mTOR, and E-cadherin were found following H2O2 treatment, and all of these were reversed by Dex. Dex also prevented the ROS generation, cytochrome C release, and cell cycle arrest induced by H2O2. The effects of Dex were partially reversed by atipamezole. Conclusion. Our study demonstrated that Dex protected lung alveolar epithelial cells from apoptotic injury, cell cycle arrest, and loss of cell adhesion induced by H2O2 through enhancing the cell survival and proliferation.

  18. In vivo metabolism of pulmonary alveolar epithelial type II pneumonocytes and macrophages from Syrian hamsters

    International Nuclear Information System (INIS)

    Pfleger, R.C.; Waide, J.J.

    1976-01-01

    Young adult Syrian hamsters were injected intraperitoneally with 14 C-glycerol and 3 H-palmitate 17 hr before they were sacrificed and pulmonary alveolar epithelial type II cells and pulmonary alveolar macrophages (PAM) were isolated. Incorporation of the two labeled components into the cellular lipids showed that the 3 H-specific activity of the phospholipids from the type II cells was three times that of the PAM and the utilization of 14 C-glycerol into phosphatidyl choline (PC) was 50% greater than incorporation into the PC from PAMs. The PC from type II cells showed that 30% was disaturated and from PAMs 21% was disaturated. Another phosphatide, phosphatidyl glycerol contained about one-third of the molecules in disaturated form. These data are consistent with the view that both type II cells and PAMs can synthesize surface-active phospholipids but it is generally accepted that only the pulmonary alveolar epithelial type II cells excrete the disaturated phospholipids which comprise the surface-active components of pulmonary surfactant

  19. Ozone exposure increases respiratory epithelial permeability in humans

    International Nuclear Information System (INIS)

    Kehrl, H.R.; Vincent, L.M.; Kowalsky, R.J.; Horstman, D.H.; O'Neil, J.J.; McCartney, W.H.; Bromberg, P.A.

    1987-01-01

    Ozone is a respiratory irritant that has been shown to cause an increase in the permeability of the respiratory epithelium in animals. We used inhaled aerosolized /sup 99m/Tc-labeled diethylene triamine pentacetic acid (/sup 99m/Tc-DTPA) to investigate whether human respiratory epithelial permeability is similarly affected by exposure to ozone. In a randomized, crossover double-blinded study, 8 healthy, nonsmoking young men were exposed for 2 h to purified air and 0.4 ppm ozone while performing intermittent high intensity treadmill exercise (minute ventilation = 66.8 L/min). SRaw and FVC were measured before and at the end of exposures. Seventy-five minutes after the exposures, the pulmonary clearance of /sup 99m/Tc-DTPA was measured by sequential posterior lung imaging with a computer-assisted gamma camera. Ozone exposure caused respiratory symptoms in all 8 subjects and was associated with a 14 +/- 2.8% (mean +/- SEM) decrement in FVC (p less than 0.001) and a 71 +/- 22% increase in SRaw (p = 0.04). Compared with the air exposure day, 7 of the 8 subjects showed increased /sup 99m/Tc-DTPA clearance after the ozone exposure, with the mean value increasing from 0.59 +/- 0.08 to 1.75 +/- 0.43%/min (p = 0.03). These data show that ozone exposure sufficient to produce decrements in the pulmonary function of human subjects also causes an increase in /sup 99m/Tc-DTPA clearance

  20. TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.

    Science.gov (United States)

    Kannler, Martina; Lüling, Robin; Yildirim, Ali Önder; Gudermann, Thomas; Steinritz, Dirk; Dietrich, Alexander

    2018-05-12

    Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells. We quantified changes in intracellular Ca 2+ ([Ca 2+ ] i ) levels induced by application of hyperoxic solutions in primary tracheal epithelial, bronchial epithelial, and AT II cells isolated from wild-type (WT) and TRPA1-deficient (TRPA1-/-) mouse lungs. In all cell types, we detected hyperoxia-induced rises in [Ca 2+ ] i levels, which were not significantly different in TRPA1-deficient cells compared to WT cells. We also tested TRPA1 function in a mouse model for hyperoxia-induced alveolar epithelial hyperplasia. A characteristic significant increase in thickening of alveolar tissues was detected in mouse lungs after exposure to hyperoxia, but not in normoxic WT and TRPA1-/- controls. Quantification of changes in lung morphology in hyperoxic WT and TRPA1-/- mice, however, again revealed no significant changes. Therefore, TRPA1 expression does neither appear to be a key player for hyperoxia-induced changes in [Ca 2+ ] i levels in primary lung epithelial cells, nor being essential for the development of hyperoxia-induced alveolar epithelial hyperplasia.

  1. Establishment and evaluation of a stable cattle type II alveolar epithelial cell line.

    Directory of Open Access Journals (Sweden)

    Feng Su

    Full Text Available Macrophages and dendritic cells are recognized as key players in the defense against mycobacterial infection. Recent research has confirmed that alveolar epithelial cells (AECs also play important roles against mycobacterium infections. Thus, establishing a stable cattle AEC line for future endogenous immune research on bacterial invasion is necessary. In the present study, we first purified and immortalized type II AECs (AEC II cells by transfecting them with a plasmid containing the human telomerase reverse trancriptase gene. We then tested whether or not the immortalized cells retained the basic physiological properties of primary AECs by reverse-transcription polymerase chain reaction and Western blot. Finally, we tested the secretion capacity of immortalized AEC II cells upon stimulation by bacterial invasion. The cattle type II alveolar epithelial cell line (HTERT-AEC II that we established retained lung epithelial cell characteristics: the cells were positive for surfactants A and B, and they secreted tumor necrosis factor-α and interleukin-6 in response to bacterial invasion. Thus, the cell line we established is a potential tool for research on the relationship between AECs and Mycobacterium tuberculosis.

  2. Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells.

    Science.gov (United States)

    Danelishvili, Lia; McGarvey, Jeffery; Li, Yong-Jun; Bermudez, Luiz E

    2003-09-01

    Mycobacterium tuberculosis interacts with macrophages and epithelial cells in the alveolar space of the lung, where it is able to invade and replicate in both cell types. M. tuberculosis-associated cytotoxicity to these cells has been well documented, but the mechanisms of host cell death are not well understood. We examined the induction of apoptosis and necrosis of human macrophages (U937) and type II alveolar epithelial cells (A549) by virulent (H37Rv) and attenuated (H37Ra) M. tuberculosis strains. Apoptosis was determined by both enzyme-linked immunosorbent assay (ELISA) and TdT-mediated dUTP nick end labelling (TUNEL) assay, whereas necrosis was evaluated by the release of lactate dehydrogenase (LDH). Both virulent and attenuated M. tuberculosis induced apoptosis in macrophages; however, the attenuated strain resulted in significantly more apoptosis than the virulent strain after 5 days of infection. In contrast, cytotoxicity of alveolar cells was the result of necrosis, but not apoptosis. Although infection with M. tuberculosis strains resulted in apoptosis of 14% of the cells on the monolayer, cell death associated with necrosis was observed in 59% of alveolar epithelial cells after 5 days of infection. Infection with M. tuberculosis suppressed apoptosis of alveolar epithelial cells induced by the kinase inhibitor, staurosporine. Because our findings suggest that M. tuberculosis can modulate the apoptotic response of macrophages and epithelial cells, we carried out an apoptosis pathway-specific cDNA microarray analysis of human macrophages and alveolar epithelial cells. Whereas the inhibitors of apoptosis, bcl-2 and Rb, were upregulated over 2.5-fold in infected (48 h) alveolar epithelial cells, the proapoptotic genes, bad and bax, were downregulated. The opposite was observed when U937 macrophages were infected with M. tuberculosis. Upon infection of alveolar epithelial cells with M. tuberculosis, the generation of apoptosis, as determined by the

  3. The influence of age on lung epithelial permeability

    International Nuclear Information System (INIS)

    Yang Minfu; Wang Daoyu; Liu Xiujie; He Zuoxiang; Wang Yuetao; Wang Shiwen

    2007-01-01

    Objective: The pulmonary clearance rate of aerosolized 99 Tc m -DTPA is a sensitive index for measurement of lung epithelial permeability (LEP). It is well established that LEP increases in some pathological conditions. However, little is known about the influence of age on LEP. Accordingly, the aim of this study was to evaluate the relationship between age and LEP in healthy nonsmokers. Methods: Seventy-nine healthy nonsmokers underwent 99 Tc m -DTPA inhalation imaging and pulmonary clearance index (k) was calculated. The following analyses were done: (1) To compare the difference of k values between aged (≥ 65 years) and non-aged ( 0 + b 1 x + b 2 x 2 + b 3 x 3 , y symbolized k values and x symbolized age). Conclusions: The data of LEP at different age groups showed negative correlation of LEP and age in non-smokers. This data might play an age-related reference data in investigating senescence and lung disease in non-smokers. (authors)

  4. Decreased CXCL12 is associated with impaired alveolar epithelial cell migration and poor lung healing after lung resection.

    Science.gov (United States)

    Kanter, Jacob A; Sun, Haiying; Chiu, Stephen; DeCamp, Malcolm M; Sporn, Peter H S; Sznajder, Jacob I; Bharat, Ankit

    2015-10-01

    Prolonged air leak (PAL) is an important cause of morbidity and mortality after lung resection, but its pathogenesis has not been elucidated. Migration of alveolar type II epithelial cells is essential for lung wound repair. Here we determined the role of C-X-C motif chemokine 12 (CXCL12) on alveolar epithelial cell migration and lung wound healing. CXCL12 in the pleural fluid of patients was analyzed using enzyme-linked immunosorbent assay. Human A549 and murine MLE12 alveolar epithelial cell lines were used for wound closure, cell migration, and proliferation assays. Western blot was used to analyze Rac1 and cofilin. Pleural CXCL12 was decreased in patients with PAL (1,389 ± 192 vs 3,270 ± 247 pg/mL; P alveolar epithelial cell migration by binding to its receptor CXCR4 and may have a role in lung healing. CXCL12-mediated alveolar epithelial cell migration is associated with Rac1 and cofilin activation. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Donaldson Ken

    2005-12-01

    Full Text Available Abstract Background Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants which can recruit alveolar macrophages to sites of particle deposition. The aim of this study was to assess the responses of a type II epithelial cell line (L-2 to both fine and nanoparticle exposure in terms of secretion of chemotactic substances capable of inducing macrophage migration. Results Exposure of type II cells to carbon black nanoparticles resulted in significant release of macrophage chemoattractant compared to the negative control and to other dusts tested (fine carbon black and TiO2 and nanoparticle TiO2 as measured by macrophage migration towards type II cell conditioned medium. SDS-PAGE analysis of the conditioned medium from particle treated type II cells revealed that a higher number of protein bands were present in the conditioned medium obtained from type II cells treated with nanoparticle carbon black compared to other dusts tested. Size-fractionation of the chemotaxin-rich supernatant determined that the chemoattractants released from the epithelial cells were between 5 and 30 kDa in size. Conclusion The highly toxic nature and reactive surface chemistry of the carbon black nanoparticles has very likely induced the type II cell line to release pro-inflammatory mediators that can potentially induce migration of macrophages. This could aid in the rapid recruitment of inflammatory cells to sites of particle deposition and the subsequent removal of the particles by phagocytic cells such as macrophages and neutrophils. Future studies in this area could focus on the exact identity of the substance(s released by the

  6. Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide

    International Nuclear Information System (INIS)

    Huang, Chunrong; Zheng, Haichong; He, Wanmei; Lu, Guifang; Li, Xia; Deng, Yubin; Zeng, Mian

    2016-01-01

    Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI. -- Graphical abstract: Ghrelin ameliorates the human alveolar epithelial A549 cells apoptosis induced by lipopolysaccharide partly through activating the PI3K/Akt and ERK pathway. Display Omitted -- Highlights: •It has been observed that LPS insult significantly increased apoptosis in A549 cells. •Both Akt and ERK signaling are critical adapter molecules to mediate the ghrelin-mediated proliferative effect. •Ghrelin may have a therapeutic effect in the prevention of LPS-induced apoptosis.

  7. Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide

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    Huang, Chunrong; Zheng, Haichong; He, Wanmei; Lu, Guifang; Li, Xia [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Deng, Yubin, E-mail: dengyub@mail.sysu.edu.cn [Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Zeng, Mian, E-mail: zengmian2004@163.com [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China)

    2016-05-20

    Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI. -- Graphical abstract: Ghrelin ameliorates the human alveolar epithelial A549 cells apoptosis induced by lipopolysaccharide partly through activating the PI3K/Akt and ERK pathway. Display Omitted -- Highlights: •It has been observed that LPS insult significantly increased apoptosis in A549 cells. •Both Akt and ERK signaling are critical adapter molecules to mediate the ghrelin-mediated proliferative effect. •Ghrelin may have a therapeutic effect in the prevention of LPS-induced apoptosis.

  8. Alveolar epithelial type II cells induce T cell tolerance to specific antigen

    DEFF Research Database (Denmark)

    Lo, Bernice; Hansen, Søren; Evans, Kathy

    2008-01-01

    The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type II cells (Type...... II) constitutively express the class II MHC led us to hypothesize that Type II cells play a role in the adaptive immune response. Because Type II cells do not express detectable levels of the costimulatory molecules CD80 and CD86, we propose that Type II cells suppress activation of naive T cells...

  9. Pulmonary epithelial permeability in normal subjects and patients with idiopathic interstitial pneumonia

    International Nuclear Information System (INIS)

    Anazawa, Yoshiki; Isawa, Toyoharu; Teshima, Takeo; Miki, Makoto; Motomiya, Masakichi

    1991-01-01

    99m Tc-DTPA is a low molecular weight substance, which is believed to pass through the pulmonary epithelium when it is inhaled as an aerosol. We performed 99m Tc-DTPA inhalation studies in 10 nonsmoking normal subjects and 10 patients with biopsy proven idiopathic interstitial pneumonia prior to therapy. 99m Tc-DTPA aerosol was inhaled for 3 min with the subject in the supine position and radioactivity was measured anteriorly with a gamma camera and recorded on computer. Measurements were performed for 3 min with the subject inhaling aerosol and for the subsequent 30 min with the subject in the same position. Time activity curves from the five regions of interest (ROIs) including the entire left lung, the entire right lung, and the upper, middle and lower third of the right lung were separately fitted to a single exponential function for the initial 7 min following cessation of inhalation, and the respective clearance half life (t1/2) in min was calculated. Lung function data, arterial blood gas tensions and blood chemistry were also obtained for comparison with the t1/2 values. The t1/2 values were significantly smaller in all ROIs in patients with idiopathic interstitial pneumonia than in normal subjects, indicating an increased pulmonary epithelial permeability in these patients. There was no relationship between t1/2 and %DL co , %DL co /V A , PaO 2 , or LDH. Although the true pathophysiologic significance of t1/2 measured using 99m Tc-DTPA aerosol is still not known, we consider that this measurement may be an important indicator of nonrespiratory lung function, in particular the degree of alveolar epithelial damage. (author)

  10. Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells.

    Science.gov (United States)

    Armstrong, Lynne; Medford, Andrew R L; Uppington, Kay M; Robertson, John; Witherden, Ian R; Tetley, Teresa D; Millar, Ann B

    2004-08-01

    The recognition of potentially harmful microorganisms involves the specific recognition of pathogen-associated molecular patterns (PAMPs) and the family of Toll-like receptors (TLRs) is known to play a central role in this process. TLR-4 is the major recognition receptor for lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, whereas TLR-2 responds to bacterial products from gram-positive organisms. Although resident alveolar macrophages are the first line of defense against microbial attack, it is now understood that the alveolar epithelium also plays a pivotal role in the innate immunity of the lung. The purpose of the current study was to determine whether human primary type II alveolar epithelial cells (ATII) express functional TLR-2 and TLR-4 and how they may be regulated by inflammatory mediators. We have used reverse transcriptase-polymerase chain reaction and flow cytometry to determine basal and inducible expression on ATII. We have used highly purified preparations of the gram-positive bacterial product lipoteichoic acid (LTA) and LPS to look at the functional consequences of TLR-2 and TLR-4 ligation, respectively, in terms of interleukin-8 release. We have shown that human primary ATII cells express mRNA and protein for both TLR-2 and TLR-4, which can be modulated by incubation with LPS and tumor necrosis factor. Furthermore, we have demonstrated that these receptors are functional. This suggests that ATII have the potential to contribute significantly to the host defense of the human alveolus against bacteria.

  11. Disruption of sorting nexin 5 causes respiratory failure associated with undifferentiated alveolar epithelial type I cells in mice.

    Directory of Open Access Journals (Sweden)

    Sun-Kyoung Im

    Full Text Available Sorting nexin 5 (Snx5 has been posited to regulate the degradation of epidermal growth factor receptor and the retrograde trafficking of cation-independent mannose 6-phosphate receptor/insulin-like growth factor II receptor. Snx5 has also been suggested to interact with Mind bomb-1, an E3 ubiquitin ligase that regulates the activation of Notch signaling. However, the in vivo functions of Snx5 are largely unknown. Here, we report that disruption of the Snx5 gene in mice (Snx5(-/- mice resulted in partial perinatal lethality; 40% of Snx5(-/- mice died shortly after birth due to cyanosis, reduced air space in the lungs, and respiratory failure. Histological analysis revealed that Snx5(-/- mice exhibited thickened alveolar walls associated with undifferentiated alveolar epithelial type I cells. In contrast, alveolar epithelial type II cells were intact, exhibiting normal surfactant synthesis and secretion. Although the expression levels of surfactant proteins and saturated phosphatidylcholine in the lungs of Snx5(-/- mice were comparable to those of Snx5(+/+ mice, the expression levels of T1α, Aqp5, and Rage, markers for distal alveolar epithelial type I cells, were significantly decreased in Snx5 (-/- mice. These results demonstrate that Snx5 is necessary for the differentiation of alveolar epithelial type I cells, which may underlie the adaptation to air breathing at birth.

  12. Evidence for the involvement of cofilin in Aspergillus fumigatus internalization into type II alveolar epithelial cells.

    Science.gov (United States)

    Bao, Zhiyao; Han, Xuelin; Chen, Fangyan; Jia, Xiaodong; Zhao, Jingya; Zhang, Changjian; Yong, Chen; Tian, Shuguang; Zhou, Xin; Han, Li

    2015-08-13

    The internalization of Aspergillus fumigatus into alveolar epithelial cells (AECs) is tightly controlled by host cellular actin dynamics, which require close modulation of the ADF (actin depolymerizing factor)/cofilin family. However, the role of cofilin in A. fumigatus internalization into AECs remains unclear. Here, we demonstrated that germinated A. fumigatus conidia were able to induce phosphorylation of cofilin in A549 cells during the early stage of internalization. The modulation of cofilin activity by overexpression, knockdown, or mutation of the cofilin gene in A549 cells decreased the efficacy of A. fumigatus internalization. Reducing the phosphorylation status of cofilin with BMS-5 (LIM kinase inhibitor) or overexpression of the slingshot phosphatases also impeded A. fumigatus internalization. Both the C. botulimun C3 transferase (a specific RhoA inhibitor) and Y27632 (a specific ROCK inhibitor) reduced the internalization of A. fumigatus and the level of phosphorylated cofilin. β-1,3-glucan (the major component of the conidial cell wall) and its host cell receptor dectin-1 did not seem to be associated with cofilin phosphorylation during A. fumigatus infection. These results indicated that cofilin might be involved in the modulation of A. fumigatus internalization into type II alveolar epithelial cells through the RhoA-ROCK-LIM kinase pathway.

  13. S-carboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human alveolar epithelial cells.

    Science.gov (United States)

    Sumitomo, Tomoko; Nakata, Masanobu; Yamaguchi, Masaya; Terao, Yutaka; Kawabata, Shigetada

    2012-01-01

    Streptococcus pneumoniae is a major pathogen of respiratory infections that utilizes platelet-activating factor receptor (PAFR) for firm adherence to host cells. The mucolytic agent S-carboxymethylcysteine (S-CMC) has been shown to exert inhibitory effects against infection by several respiratory pathogens including S. pneumoniae in vitro and in vivo. Moreover, clinical studies have implicated the benefits of S-CMC in preventing exacerbation of chronic obstructive pulmonary disease, which is considered to be related to respiratory infections. In this study, to assess whether the potency of S-CMC is attributable to inhibition of pneumococcal adherence to host cells, an alveolar epithelial cell line stimulated with interleukin-1α was used as a model of inflamed epithelial cells. Despite upregulation of PAFR by inflammatory activation, treatment with S-CMC efficiently inhibited pneumococcal adherence to host epithelial cells. In order to gain insight into the inhibitory mechanism, the effects of S-CMC on PAFR expression were also investigated. Following treatment with S-CMC, PAFR expression was reduced at both mRNA and post-transcriptional levels. Interestingly, S-CMC was also effective in inhibiting pneumococcal adherence to cells transfected with PAFR small interfering RNAs. These results indicate S-CMC as a probable inhibitor targeting numerous epithelial receptors that interact with S. pneumoniae.

  14. Gene expression patterns induced at different stages of rhinovirus infection in human alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Etemadi

    Full Text Available Human rhinovirus (HRV is the common virus that causes acute respiratory infection (ARI and is frequently associated with lower respiratory tract infections (LRTIs. We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B. RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection. The 75 up-regulated genes surpassed the down-regulated genes (35 at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing. At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events. Our data provides a comprehensive image of host response to HRV infection. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.

  15. Injurious effects of wool and grain dusts on alveolar epithelial cells and macrophages in vitro.

    Science.gov (United States)

    Brown, D M; Donaldson, K

    1991-01-01

    Epidemiological studies of workers in wool textile mills have shown a direct relation between the concentration of wool dust in the air and respiratory symptoms. Injurious effects of wool dust on the bronchial epithelium could be important in causing inflammation and irritation. A pulmonary epithelial cell line in vitro was therefore used to study the toxic effects of wool dust. Cells of the A549 epithelial cell line were labelled with 51Cr and treated with whole wool dusts and extracts of wool, after which injury was assessed. Also, the effects of grain dust, which also causes a form of airway obstruction, were studied. The epithelial injury was assessed by measuring 51Cr release from cells as an indication of lysis, and by monitoring cells which had detached from the substratum. No significant injury to A549 cells was caused by culture with any of the dusts collected from the air but surface "ledge" dust caused significant lysis at some doses. Quartz, used as a toxic control dust, caused significant lysis at the highest concentration of 100 micrograms/well. To determine whether any injurious material was soluble the dusts were incubated in saline and extracts collected. No extracts caused significant injury to epithelial cells. A similar lack of toxicity was found when 51Cr labelled control alveolar macrophages were targets for injury. Significant release of radiolabel was evident when macrophages were exposed to quartz at concentrations of 10 and 20 micrograms/well, there being no significant injury with either wool or grain dusts. These data suggest that neither wool nor grain dust produce direct injury to epithelial cells, and further studies are necessary to explain inflammation leading to respiratory symptoms in wool and grain workers. PMID:2015211

  16. A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing.

    Science.gov (United States)

    Ghosh, Manik C; Makena, Patrudu S; Kennedy, Joseph; Teng, Bin; Luellen, Charlean; Sinclair, Scott E; Waters, Christopher M

    2017-05-19

    Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4. In addition, protein phosphatase-5 (PP5) increased its association with this heteromeric complex, while apoptosis signal regulating kinase-1 (ASK1) dissociated from the complex. Cell migration following wounding was decreased when PP5 expression was decreased using shRNA, but migration was increased in ATII cells isolated from ASK1 knockout mice. Interactions between FAK and CXCR4 were increased upon depletion of ASK1 using shRNA in MLE-12 cells, but unaffected when PP5 was depleted. Furthermore, we found that wounded rat ATII cells exhibited decreased ASK1 phosphorylation at Serine-966, decreased serine phosphorylation of FAK, and decreased association of phosphorylated ASK1 with FAK. These changes in phosphorylation were dependent upon expression of PP5. These results demonstrate a unique molecular complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing.

  17. Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling.

    Science.gov (United States)

    Ito, Yoko; Correll, Kelly; Schiel, John A; Finigan, Jay H; Prekeris, Rytis; Mason, Robert J

    2014-07-01

    There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS. Copyright © 2014 the American Physiological Society.

  18. Effects of PPARγ ligands on TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells

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    Dagher Hayat

    2010-02-01

    Full Text Available Abstract Background Transforming growth factor β1 (TGF-β1-mediated epithelial mesenchymal transition (EMT of alveolar epithelial cells (AEC may contribute to lung fibrosis. Since PPARγ ligands have been shown to inhibit fibroblast activation by TGF-β1, we assessed the ability of the thiazolidinediones rosiglitazone (RGZ and ciglitazone (CGZ to regulate TGF-β1-mediated EMT of A549 cells, assessing changes in cell morphology, and expression of cell adhesion molecules E-cadherin (epithelial cell marker and N-cadherin (mesenchymal cell marker, and collagen 1α1 (COL1A1, CTGF and MMP-2 mRNA. Methods Serum-deprived A549 cells (human AEC cell line were pre-incubated with RGZ and CGZ (1 - 30 μM in the absence or presence of the PPARγ antagonist GW9662 (10 μM before TGFβ-1 (0.075-7.5 ng/ml treatment for up to 72 hrs. Changes in E-cadherin, N-cadherin and phosphorylated Smad2 and Smad3 levels were analysed by Western blot, and changes in mRNA levels including COL1A1 assessed by RT-PCR. Results TGFβ-1 (2.5 ng/ml-induced reductions in E-cadherin expression were associated with a loss of epithelial morphology and cell-cell contact. Concomitant increases in N-cadherin, MMP-2, CTGF and COL1A1 were evident in predominantly elongated fibroblast-like cells. Neither RGZ nor CGZ prevented TGFβ1-induced changes in cell morphology, and PPARγ-dependent inhibitory effects of both ligands on changes in E-cadherin were only evident at submaximal TGF-β1 (0.25 ng/ml. However, both RGZ and CGZ inhibited the marked elevation of N-cadherin and COL1A1 induced by TGF-β1 (2.5 ng/ml, with effects on COL1A1 prevented by GW9662. Phosphorylation of Smad2 and Smad3 by TGF-β1 was not inhibited by RGZ or CGZ. Conclusions RGZ and CGZ inhibited profibrotic changes in TGF-β1-stimulated A549 cells independently of inhibition of Smad phosphorylation. Their inhibitory effects on changes in collagen I and E-cadherin, but not N-cadherin or CTGF, appeared to be PPAR

  19. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Yuen Kit M

    2009-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  20. Dopamine enhances duodenal epithelial permeability via the dopamine D5 receptor in rodent.

    Science.gov (United States)

    Feng, X-Y; Zhang, D-N; Wang, Y-A; Fan, R-F; Hong, F; Zhang, Y; Li, Y; Zhu, J-X

    2017-05-01

    The intestinal barrier is made up of epithelial cells and intercellular junctional complexes to regulate epithelial ion transport and permeability. Dopamine (DA) is able to promote duodenal epithelial ion transport through D1-like receptors, which includes subtypes of D 1 (D 1 R) and D 5 (D 5 R), but whether D1-like receptors influence the duodenal permeability is unclear. FITC-dextran permeability, short-circuit current (I SC ), Western blot, immunohistochemistry and ELISA were used in human D 5 R transgenic mice and hyperendogenous enteric DA (HEnD) rats in this study. Dopamine induced a downward deflection in I SC and an increase in FITC-dextran permeability of control rat duodenum, which were inhibited by the D1-like receptor antagonist, SCH-23390. However, DA decreased duodenal transepithelial resistance (TER), an effect also reversed by SCH-23390. A strong immunofluorescence signal for D 5 R, but not D 1 R, was observed in the duodenum of control rat. In human D 5 R knock-in transgenic mice, duodenal mucosa displayed an increased basal I SC with high FITC-dextran permeability and decreased TER with a lowered expression of tight junction proteins, suggesting attenuated duodenal barrier function in these transgenic mice. D 5 R knock-down transgenic mice manifested a decreased basal I SC with lowered FITC-dextran permeability. Moreover, an increased FITC-dextran permeability combined with decreased TER and tight junction protein expression in duodenal mucosa were also observed in HEnD rats. This study demonstrates, for the first time, that DA enhances duodenal permeability of control rat via D 5 R, which provides new experimental and theoretical evidence for the influence of DA on duodenal epithelial barrier function. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. Protein Expression Profile of Rat Type Two Alveolar Epithelial Cells During Hyperoxic Stress and Recovery

    Science.gov (United States)

    Bhargava, Maneesh

    Rationale: In rodent model systems, the sequential changes in lung morphology resulting from hyperoxic injury are well characterized, and are similar to changes in human acute respiratory distress syndrome (ARDS). In the injured lung, alveolar type two (AT2) epithelial cells play a critical role restoring the normal alveolar structure. Thus characterizing the changes in AT2 cells will provide insights into the mechanisms underpinning the recovery from lung injury. Methods: We applied an unbiased systems level proteomics approach to elucidate molecular mechanisms contributing to lung repair in a rat hyperoxic lung injury model. AT2 cells were isolated from rat lungs at predetermined intervals during hyperoxic injury and recovery. Protein expression profiles were determined by using iTRAQRTM with tandem mass spectrometry. Results: Of 959 distinct proteins identified, 183 significantly changed in abundance during the injury-recovery cycle. Gene Ontology enrichment analysis identified cell cycle, cell differentiation, cell metabolism, ion homeostasis, programmed cell death, ubiquitination, and cell migration to be significantly enriched by these proteins. Gene Set Enrichment Analysis of data acquired during lung repair revealed differential expression of gene sets that control multicellular organismal development, systems development, organ development, and chemical homeostasis. More detailed analysis identified activity in two regulatory pathways, JNK and miR 374. A Short Time-series Expression Miner (STEM) algorithm identified protein clusters with coherent changes during injury and repair. Conclusion: Coherent changes occur in the AT2 cell proteome in response to hyperoxic stress. These findings offer guidance regarding the specific molecular mechanisms governing repair of the injured lung.

  2. Spatiotemporal dynamics of actin remodeling and endomembrane trafficking in alveolar epithelial type I cell wound healing.

    Science.gov (United States)

    Godin, Lindsay M; Vergen, Jorge; Prakash, Y S; Pagano, Richard E; Hubmayr, Rolf D

    2011-04-01

    Alveolar epithelial type I cell (ATI) wounding is prevalent in ventilator-injured lungs and likely contributes to pathogenesis of "barotrauma" and "biotrauma." In experimental models most wounded alveolar cells repair plasma membrane (PM) defects and survive insults. Considering the force balance between edge energy at the PM wound margins and adhesive interactions of the lipid bilayer with the underlying cytoskeleton (CSK), we tested the hypothesis that subcortical actin depolymerization is a key facilitator of PM repair. Using real-time fluorescence imaging of primary rat ATI transfected with a live cell actin-green fluorescent protein construct (Lifeact-GFP) and loaded with N-rhodamine phosphatidylethanolamine (PE), we examined the spatial and temporal coordination between cytoskeletal remodeling and PM repair following micropuncture. Membrane integrity was inferred from the fluorescence intensity profiles of the cytosolic label calcein AM. Wounding led to rapid depolymerization of the actin CSK near the wound site, concurrent with accumulation of endomembrane-derived N-rhodamine PE. Both responses were sustained until PM integrity was reestablished, which typically occurs between ∼10 and 40 s after micropuncture. Only thereafter did the actin CSK near the wound begin to repolymerize, while the rate of endomembrane lipid accumulation decreased. Between 60 and 90 s after successful PM repair, after translocation of the actin nucleation factor cortactin, a dense actin fiber network formed. In cells that did not survive micropuncture injury, actin remodeling did not occur. These novel results highlight the importance of actin remodeling in ATI cell repair and suggest molecular targets for modulating the repair process.

  3. Autophagy protects type II alveolar epithelial cells from Mycobacterium tuberculosis infection

    International Nuclear Information System (INIS)

    Guo, Xu-Guang; Ji, Tian-Xing; Xia, Yong; Ma, Yue-Yun

    2013-01-01

    Highlights: ► We investigated the protective effect of autophagy pathway against MTB infection. ► MTB-infected A549 cells had higher LDH release. ► Inhibition of autophagy signaling significantly enhanced the MTB-induced necrosis. ► Autophagy prevents apoptosis and promotes cell survival in infected cells. -- Abstract: This study was designed to investigate the protective effect of the autophagy signaling pathway against Mycobacterium tuberculosis infection in type II alveolar epithelial cells. An in vitro M. tuberculosis system was established using human A549 cells. Infection-induced changes in the expression of the autophagic marker LC3 were assessed by reverse transcription-PCR and Western blotting. Morphological changes in autophagosomes were detected by transmission electron microscopy (TEM). The function of the autophagy signaling pathway during infection was assessed by measuring the level of cell death and the amount of lactate dehydrogenase (LDH) released in the presence or absence of the inhibitor 3-methyladenine (3-MA). In addition, effects on LDH release were assessed after the siRNA-mediated knockdown of the essential autophagosomal structural membrane protein Atg5. LC3 mRNA expression was significantly reduced in M.tuberculosis-infected A549 cells (16888.76 ± 1576.34 vs. uninfected: 12744.29 ± 1089.37; P < 0.05). TEM revealed M.tuberculosis bacilli-containing compartments that were surrounded by double membranes characteristic of the autophagic process. M.tuberculosis-infected A549 cells released more LDH (1.45 ± 0.12 vs. uninfected: 0.45 ± 0.04; P < 0.05). The inhibition of autophagy signaling significantly enhanced M.tuberculosis-induced necrosis (3-MA: 75 ± 5% vs. untreated: 15 ± 1%; P < 0.05) and LDH release (3-MA: 2.50 ± 0.24 vs. untreated: 0.45 ± 0.04; Atg5 knockdown: 3.19 ± 0.29 vs. untreated: 1.28 ± 0.11; P < 0.05). Our results indicate that autophagy signaling pathway prevents apoptosis in type II alveolar epithelial cells

  4. Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions.

    Science.gov (United States)

    Lechuga, Susana; Baranwal, Somesh; Ivanov, Andrei I

    2015-05-01

    Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. Copyright © 2015 the American Physiological Society.

  5. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.

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    Katrin Högner

    2013-02-01

    Full Text Available Influenza viruses (IV cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL. Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR- and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.

  6. Silencing hyperoxia-induced C/EBPα in neonatal mice improves lung architecture via enhanced proliferation of alveolar epithelial cells

    Science.gov (United States)

    Yang, Guang; Hinson, Maurice D.; Bordner, Jessica E.; Lin, Qing S.; Fernando, Amal P.; La, Ping; Wright, Clyde J.

    2011-01-01

    Postnatal lung development requires proliferation and differentiation of specific cell types at precise times to promote proper alveolar formation. Hyperoxic exposure can disrupt alveolarization by inhibiting cell growth; however, it is not fully understood how this is mediated. The transcription factor CCAAT/enhancer binding protein-α (C/EBPα) is highly expressed in the lung and plays a role in cell proliferation and differentiation in many tissues. After 72 h of hyperoxia, C/EBPα expression was significantly enhanced in the lungs of newborn mice. The increased C/EBPα protein was predominantly located in alveolar type II cells. Silencing of C/EBPα with a transpulmonary injection of C/EBPα small interfering RNA (siRNA) prior to hyperoxic exposure reduced expression of markers of type I cell and differentiation typically observed after hyperoxia but did not rescue the altered lung morphology at 72 h. Nevertheless, when C/EBPα hyperoxia-exposed siRNA-injected mice were allowed to recover for 2 wk in room air, lung epithelial cell proliferation was increased and lung morphology was restored compared with hyperoxia-exposed control siRNA-injected mice. These data suggest that C/EBPα is an important regulator of postnatal alveolar epithelial cell proliferation and differentiation during injury and repair. PMID:21571903

  7. Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

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    Hiroshi Kondo

    2015-01-01

    Full Text Available Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated an in vitro system to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12 were further analyzed. Under serum-free culture conditions, surfactant protein C (SPC, an ATII marker, was upregulated in both H12 and B7. Aquaporin 5 (AQP5, an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited, SPC and thyroid transcription factor-1 (TTF-1 expression levels were enhanced. After treatment with dexamethasone (DEX, 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP, 3-isobutyl-1-methylxanthine (IBMX, and keratinocyte growth factor (KGF, surfactant protein B and TTF-1 expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

  8. Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice

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    Danyi Peng

    2017-12-01

    Full Text Available Alveolar epithelial cells (AECs injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF. Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO7-Cre/SMARCA4f/f mice (SOSM4Δ/Δ model, as well as a new SMARCA4-deleted alveolar type II (ATII-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.

  9. Epithelial Permeability Alterations in an In Vitro Air-Liquid Interface Model of Allergic Fungal Rhinosinusitis

    Science.gov (United States)

    Den Beste, Kyle A.; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma; Wise, Sarah K.

    2012-01-01

    Background Chronic rhinosinusitis (CRS) is an inflammatory upper-airway disease with numerous etiologies. Patients with a characteristic subtype of CRS, allergic fungal rhinosinusitis (AFRS), display increased expression of Th2 cytokines and antigen-specific IgE. Various sinonasal inflammatory conditions are associated with alterations in epithelial barrier function. The aim of this study was to compare epithelial permeability and intercellular junctional protein expression amongst cultured primary sinonasal cells from AFRS patients versus non-inflammatory controls. Methods Epithelial cells isolated from paranasal sinus mucosa of AFRS and non-inflammatory control patients were grown to confluence on permeable supports and transitioned to air-liquid interface (ALI). Trans-epithelial resistance (TER) was measured with a horizontal Ussing chamber to characterize the functional permeability of each cell type. After TER recordings were complete, a panel of intercellular junctional proteins was assessed by Western blot and immunofluorescence labeling followed by confocal microscopy. Results After 12 samples were measured from each group, we observed a 41% mean decrease in TER in AFRS cells (296±89 ohms × cm2) compared to control (503±134 ohms × cm2, P=0.006). TER deficits observed in AFRS were associated with decreased expression of the tight junction proteins occludin and Junctional Adhesion Molecule-A (JAM-A), and increased expression of a leaky tight junction protein claudin-2. Conclusions Cultured sinonasal epithelium from AFRS patients displayed increased epithelial permeability and altered expression of intercellular junctional proteins. Given that these cells were not incubated with inflammatory cytokines in vitro, the cultured AFRS epithelial alterations may represent a retained modification in protein expression from the in vivo phenotype. PMID:22927233

  10. The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis

    Science.gov (United States)

    Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P.; Williams, David B.; Kamp, David W.

    2015-01-01

    Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1) and mitochondrial aconitase (ACO-2) in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT) family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer. PMID:26370974

  11. Effect of ionising radiation exposure on structure and permeability of epithelial junctions in rat ileum

    International Nuclear Information System (INIS)

    Lebrum, F.; Dublineau, I.; Grison, S.; Strup, C.; Griffiths, N.M.

    2002-01-01

    Exposure of the digestive tract to ionising radiation results in both morphological and functional alterations of the small intestine. However little is known about the effect of irradiation on the junctions playing a major role in the maintenance of epithelial barrier integrity. Thus the aim of this study was to investigate, in rat ileum, the effect of radiation exposure on the permeability of the epithelial barrier in parallel with the localization of certain inter- and intra-cellular proteins of tight and adherent junctions

  12. Effect of SLC34A2 gene mutation on extracellular phosphorus transport in PAM alveolar epithelial cells.

    Science.gov (United States)

    Ma, Tiangang; Qu, Danhua; Yan, Bingdi; Zhang, Qinghua; Ren, Jin; Hu, Yanbing

    2018-01-01

    A mutation in the IIb sodium phosphate transporter SLC34A2 gene has recently been described in pulmonary alveolar microlithiasis (PAM) patients. Experiments in this study were aimed at confirming the role of the gene product in PAM by comparing phosphorylated products in extracellular fluid of alveolar epithelial cells overexpressing the SLC34A2 gene or its mutated version. Eukaryotic expression vectors were constructed and transfected into A549 human alveolar epithelial cells. There were three groups of cells including those transfected with empty vector plasmid pcDNA3.1(+) (plasmid control group), those transfected with normal SLC34A2 gene expressed from pcDNA3.1 (normal control group), and those transfected with a version of the PAM SLC34A2 gene linked to the pcDNA3.1(+) (PAM group). Transfection efficiencies were detected by reverse transcription-polymerase chain reaction (RT-PCR). At 48 h after transfection, the concentration of inorganic phosphorus in the culture medium was detected using an automatic biochemical analyzer. Our results showed the concentration of inorganic phosphorus in the supernatant of the normal control group was significantly lower than that in the plasmid control and PAM groups (PPAM group was significantly lower than that in the plasmid control group (PPAM patients, given that the function of the phosphate transporter seems to be affected and it is conceivable that it would lead to extracellular fluid alterations in vivo .

  13. The exhibition to ozone diminishes the adherence and increases the membrane permeability of macrophages alveolar of rate

    International Nuclear Information System (INIS)

    Garcia, J.

    2000-01-01

    Ozone gas is generated photochemically in areas with high levels of automotive or industrial emissions, and causes irritation and inflammation of the airways if inhaled. Rat alveolar macrophages were obtained by lung lavage from male Sprague Dawley rats and used as a model to assess ozone induced cell damage (0,594 ppm for up to 60 minutes). Ozone exposure caused loss of cell adherence to a polystyrene substrate and increased membrane permeability, as noted by increases in specific 51 Cr release and citoplasmic calcium levels. The results indicate that the cell membrane is a target for ozone damage. Elevations of cytoplasmic calcium could mediate other macrophage responses to ozone , including eicosanoid and nitric oxide production, with concomitant decreases in phagocytic ability and superoxide production. (Author) [es

  14. Interactions of Francisella tularensis with Alveolar Type II Epithelial Cells and the Murine Respiratory Epithelium.

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    Matthew Faron

    Full Text Available Francisella tularensis is classified as a Tier 1 select agent by the CDC due to its low infectious dose and the possibility that the organism can be used as a bioweapon. The low dose of infection suggests that Francisella is unusually efficient at evading host defenses. Although ~50 cfu are necessary to cause human respiratory infection, the early interactions of virulent Francisella with the lung environment are not well understood. To provide additional insights into these interactions during early Francisella infection of mice, we performed TEM analysis on mouse lungs infected with F. tularensis strains Schu S4, LVS and the O-antigen mutant Schu S4 waaY::TrgTn. For all three strains, the majority of the bacteria that we could detect were observed within alveolar type II epithelial cells at 16 hours post infection. Although there were no detectable differences in the amount of bacteria within an infected cell between the three strains, there was a significant increase in the amount of cellular debris observed in the air spaces of the lungs in the Schu S4 waaY::TrgTn mutant compared to either the Schu S4 or LVS strain. We also studied the interactions of Francisella strains with human AT-II cells in vitro by characterizing the ability of these three strains to invade and replicate within these cells. Gentamicin assay and confocal microscopy both confirmed that F. tularensis Schu S4 replicated robustly within these cells while F. tularensis LVS displayed significantly lower levels of growth over 24 hours, although the strain was able to enter these cells at about the same level as Schu S4 (1 organism per cell, as determined by confocal imaging. The Schu S4 waaY::TrgTn mutant that we have previously described as attenuated for growth in macrophages and mouse virulence displayed interesting properties as well. This mutant induced significant airway inflammation (cell debris and had an attenuated growth phenotype in the human AT-II cells. These

  15. Topical timolol with and without benzalkonium chloride: epithelial permeability and autofluorescence of the cornea in glaucoma.

    Science.gov (United States)

    de Jong, C; Stolwijk, T; Kuppens, E; de Keizer, R; van Best, J

    1994-04-01

    Epithelial permeability and autofluorescence of the cornea were determined by fluorophotometry in 21 patients with open-angle glaucoma or ocular hypertension using timolol medication with the preservative benzalkonium chloride (BAC) and 2 weeks after changing to timolol medication without BAC. The investigation was performed to determine whether removal of BAC would reduce toxic effects on the cornea and complaints of sensations of burning or dry eye. Corneal epithelial permeability decreased significantly after changing medication (mean decrease per patient 27%, P = 0.025). Corneal autofluorescence increased significantly after changing medication suggesting an alteration in corneal metabolism (mean increase per patient 6%, P = 0.003). Timolol without BAC was found to be as effective as timolol with BAC in reducing intraocular pressure (P = 0.4). Removal of BAC from timolol resulted in an improvement of corneal epithelial barrier function and in a reduction of complaints. The improvement was found to be proportional to the duration of the preceding BAC-containing therapy.

  16. Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells

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    Peiris Malik

    2010-03-01

    Full Text Available Abstract Avian influenza virus H9N2 isolates cause a mild influenza-like illness in humans. However, the pathogenesis of the H9N2 subtypes in human remains to be investigated. Using a human alveolar epithelial cell line A549 as host, we found that A/Quail/Hong Kong/G1/97 (H9N2/G1, which shares 6 viral "internal genes" with the lethal A/Hong Kong/156/97 (H5N1/97 virus, replicates efficiently whereas other H9N2 viruses, A/Duck/Hong Kong/Y280/97 (H9N2/Y280 and A/Chicken/Hong Kong/G9/97 (H9N2/G9, replicate poorly. Interestingly, we found that there is a difference in the translation of viral protein but not in the infectivity or transcription of viral genes of these H9N2 viruses in the infected cells. This difference may possibly be explained by H9N2/G1 being more efficient on viral protein production in specific cell types. These findings suggest that the H9N2/G1 virus like its counterpart H5N1/97 may be better adapted to the human host and replicates efficiently in human alveolar epithelial cells.

  17. Alveolar Epithelial Cells in Mycobacterium tuberculosis Infection: Active Players or Innocent Bystanders?

    Science.gov (United States)

    Scordo, Julia M; Knoell, Daren L; Torrelles, Jordi B

    2016-01-01

    Tuberculosis (TB) is a disease that kills one person every 18 s. TB remains a global threat due to the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following seroconversion, and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure, which influence the extent of infection. We further discuss how the M.tb-alveolar epithelium interaction instigates cell-to-cell crosstalk that regulates the immune balance between a proinflammatory and an immunoregulatory state, thereby prohibiting or allowing the establishment of infection. We propose that consideration of alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. © 2015 S. Karger AG, Basel.

  18. Alveolar epithelial cells in Mycobacterium tuberculosis infection: Active Players or Innocent Bystanders

    Science.gov (United States)

    Scordo, Julia M.; Knoell, Daren L.; Torrelles, Jordi B.

    2015-01-01

    Tuberculosis (TB) is a disease that kills one person every 18 seconds. TB remains a global threat due to the emergence of drug resistance Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following sero-conversion and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure that influence the extent of infection. We further discuss how the M.tb-alveolar epithelia interaction instigate cell to cell crosstalk that regulates immune balance between a pro-inflammatory or immunoregulatory state thereby prohibiting or allowing the establishment of infection. We propose that consideration of the alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. PMID:26384325

  19. Role of alveolar epithelial Early growth response-1 (Egr-1) in CD8+ T Cell mediated Lung Injury

    Science.gov (United States)

    Ramana, Chilakamarti V.; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung- Joo; Enelow, Richard I.

    2009-01-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8+ T cells in this injury, and have found that the critical effector molecule is TNF-α expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8+ T cell recognition, and demonstrate that the Early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-α– dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection. PMID:19786304

  20. Role of alveolar epithelial early growth response-1 (Egr-1) in CD8+ T cell-mediated lung injury.

    Science.gov (United States)

    Ramana, Chilakamarti V; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung-Joo; Enelow, Richard I

    2009-12-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8(+) T cells in this injury, and have found that the critical effector molecule is TNF-alpha expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8(+) T cell recognition, and demonstrate that the early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-alpha-dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection.

  1. Dual role for plasminogen activator inhibitor type 1 as soluble and as matricellular regulator of epithelial alveolar cell wound healing.

    Science.gov (United States)

    Maquerlot, François; Galiacy, Stephane; Malo, Michel; Guignabert, Christophe; Lawrence, Daniel A; d'Ortho, Maria-Pia; Barlovatz-Meimon, Georgia

    2006-11-01

    Epithelium repair, crucial for restoration of alveolo-capillary barrier integrity, is orchestrated by various cytokines and growth factors. Among them keratinocyte growth factor plays a pivotal role in both cell proliferation and migration. The urokinase plasminogen activator (uPA) system also influences cell migration through proteolysis during epithelial repair. In addition, the complex formed by uPAR-uPA and matrix-bound plasminogen activator inhibitor type-1 (PAI-1) exerts nonproteolytic roles in various cell types. Here we present new evidence about the dual role of PAI-1 under keratinocyte growth factor stimulation using an in vitro repair model of rat alveolar epithelial cells. Besides proteolytic involvement of the uPA system, the availability of matrix-bound-PAI-1 is also required for an efficient healing. An unexpected decrease of healing was shown when PAI-1 activity was blocked. However, the proteolytic action of uPA and plasmin were still required. Moreover, immediately after wounding, PAI-1 was dramatically increased in the newly deposited matrix at the leading edge of wounds. We thus propose a dual role for PAI-1 in epithelial cell wound healing, both as a soluble inhibitor of proteolysis and also as a matrix-bound regulator of cell migration. Matrix-bound PAI-1 could thus be considered as a new member of the matricellular protein family.

  2. Value of Tc99m-DTPA alveolar permeability in lung involvement detection of patients with HIV infection

    International Nuclear Information System (INIS)

    Massardo Vega, Teresa; Jofre Manieu, Maria Josefina; Cabello Araya, Hernan; Sepulveda Carvajal, Cecilia; Ruiz Carmona, Mauricio; Moyano Schlegel, Leonor; Fica Cubillos, Alberto; Alay Perez, Rita

    2001-01-01

    We studied 35 HIV patients in order to know the value of Tc99mDTPA in the assessment of pulmonary lung involvement, especially pneumocystis carinii (PC) infection. Lung DTPA clearance measures increased alveolar permeability. Twenty patients with respiratory symptoms were included, 4 with systemic symptoms and also 11 asymptomatics, with similar immune condition (CD4 lymphocytes <400) as a control group. Smoking habit was suspended prior the test. Clinical follow up, chest film, induced sputum and/or fibrobronchoscopy were obtained. There was histological confirmation of PC presence or absence in 16 symptomatics and 3 asymptomatics. DTPA sensitivity for PC detection was 78%, specificity 40% and accuracy 58%; the values were 85%, 60% and 79%, respectively, for inflammatory lung processes. There were 4/6 cases false positive for PC detection with respiratory features explaining DTPA abnormalities. Concluding, Tc99m-DTPA is sensitive but not specific for detecting PC pneumonia but its value is higher for pulmonary inflammatory processes (Au)

  3. Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

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    W. Cui

    2010-04-01

    Full Text Available The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-α on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-α (10 or 100 ng/mL for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-α treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-α decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-α did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-α increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

  4. Cytotoxicity and inflammation in human alveolar epithelial cells following exposure to occupational levels of gold and silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Bachand, George D., E-mail: gdbacha@sandia.gov [Sandia National Laboratories, Center for Integrated Nanotechnologies (United States); Allen, Amy [Sandia National Laboratories, Department of Analytical Science (United States); Bachand, Marlene [Sandia National Laboratories, Department of Nanobiology (United States); Achyuthan, Komandoor E. [Sandia National Laboratories, Department of Biosensors and Nanomaterials (United States); Seagrave, Jean Clare [Lovelace Respiratory Research Institute, Applied Life Science and Toxicology Division (United States); Brozik, Susan M. [Sandia National Laboratories, Department of Biosensors and Nanomaterials (United States)

    2012-10-15

    While inhalation represents one of the most likely routes of exposure, the toxicity and response of nanoparticles at concentrations expected from such an exposure are not well understood. Here we characterized the in vitro response of human A549 adenocarcinomic alveolar epithelial cells following exposure to gold (AuNP) and silver (AgNP) nanoparticles at levels approximating an occupational exposure. Changes in neither oxidative stress nor cytotoxicity were significantly affected by exposure to AgNPs and AuNPs, regardless of NP type (Ag vs. Au), concentration, surface ligand (citrate or tannic acid), or size. An inflammatory response was, however, observed in response to 20 nm AgNPs and 20 nm AuNPs, where significant differences in the release of interleukin (IL)-8 but not IL-6 were observed. Additional data demonstrated that increased IL-8 secretion was strongly dependent on both nanoparticle size and concentration. Overall these data suggest that, while not acutely toxic, occupational exposure to AuNPs and AgNPs may trigger a significant inflammatory response in alveolar epithelium. Moreover, the differential responses in IL-8 and IL-6 secretion suggest that NPs may induce a response pathway that is distinct from those commonly elicited by allergens and pathogens.

  5. Wnt-inducible protein (WISP-1 is a key regulator of alveolar epithelial cell hyperplasia in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Melanie Königshoff

    2006-12-01

    Full Text Available Fibrotic lung disease is characterized by distorted lung architecture and severe loss of respiratory function secondary to alveolar epithelial cell (AEC hyperplasia, enhanced extracellular matrix (ECM deposition and fibroblast proliferation. Repetitive epithelial injuries with impaired alveolar wound healing and altered AEC gene expression represent a trigger mechanism for development of fibrosis. To reveal gene regulatory networks in lung fibrosis, we compared gene expression profiles of freshly isolated AEC obtained from mice 14 days after saline or bleomycin (BM instillation using whole genome microarray analysis. Several genes of the Wnt signaling pathway, in particular WISP-1, a member of the CCN family, were highly regulated. WISP-1 protein expression was demonstrated in proliferating AEC in BM-treated lungs by immunofluorescence. When analyzing all six CCN family members, WISP-1 was upregulated the most 14 days after BM challenge, as analyzed by qRT-PCR. To elucidate WISP-1 function, cultured primary mouse AEC were stimulated with WISP-1 and demonstrated a 230% increase in proliferation, analyzed by 3H-thymidine incorporation. This was mediated through enhanced phosphorylation, but not expression of protein kinase B (PKB/Akt, as detected by immunoblot. Finally, increased expression of WISP-1 was detected in lung homogenates and isolated AEC from IPF patients, using qRT-PCR. Immunohistochemical analysis of WISP-1 and Ki67 verified the existence of hyperplastic and proliferative AEC expressing WISP-1 in vivo. Our study thus identifies WISP-1 as a novel regulator of AEC injury and repair, and suggests that WISP-1 is a key mediator in pulmonary fibrosis.

  6. Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.

    Science.gov (United States)

    Dolinay, Tamas; Himes, Blanca E; Shumyatcher, Maya; Lawrence, Gladys Gray; Margulies, Susan S

    2017-08-01

    Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.

  7. Potential in vitro model for testing the effect of exposure to nanoparticles on the lung alveolar epithelial barrier

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    Raymond Derk

    2015-03-01

    Full Text Available Pulmonary barrier function plays a pivotal role in protection from inhaled particles. However, some nano-scaled particles, such as carbon nanotubes (CNT, have demonstrated the ability to penetrate this barrier in animal models, resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying mechanism and specific bio-effect of inhaled nanoparticles in respiratory toxicity, models of lung epithelial barriers are required that allow accurate representation of in vivo systems; however, there is currently a lack of consistent methods to do so. Thus, this work demonstrates a well-characterized in vitro model of pulmonary barrier function using Calu-3 cells, and provides the experimental conditions required for achieving tight junction complexes in cell culture, with trans-epithelial electrical resistance measurement used as a biosensor for proper barrier formation and integrity. The effects of cell number and serum constituents have been examined and we found that changes in each of these parameters can greatly affect barrier formation. Our data demonstrate that use of 5.0 × 104 Calu-3 cells/well in the Transwell cell culture system, with 10% serum concentrations in culture media is optimal for assessing epithelial barrier function. In addition, we have utilized CNT exposure to analyze the dose-, time-, and nanoparticle property-dependent alterations of epithelial barrier permeability as a means to validate this model. Such high throughput in vitro cell models of the epithelium could be used to predict the interaction of other nanoparticles with lung epithelial barriers to mimic respiratory behavior in vivo, thus providing essential tools and bio-sensing techniques that can be uniformly employed.

  8. Enolase 1 (ENO1 and protein disulfide-isomerase associated 3 (PDIA3 regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells

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    Kathrin Mutze

    2015-08-01

    Full Text Available The alveolar epithelium represents a major site of tissue destruction during lung injury. It consists of alveolar epithelial type I (ATI and type II (ATII cells. ATII cells are capable of self-renewal and exert progenitor function for ATI cells upon alveolar epithelial injury. Cell differentiation pathways enabling this plasticity and allowing for proper repair, however, are poorly understood. Here, we applied proteomics, expression analysis and functional studies in primary murine ATII cells to identify proteins and molecular mechanisms involved in alveolar epithelial plasticity. Mass spectrometry of cultured ATII cells revealed a reduction of carbonyl reductase 2 (CBR2 and an increase in enolase 1 (ENO1 and protein disulfide-isomerase associated 3 (PDIA3 protein expression during ATII-to-ATI cell trans-differentiation. This was accompanied by increased Wnt/β-catenin signaling, as analyzed by qRT-PCR and immunoblotting. Notably, ENO1 and PDIA3, along with T1α (podoplanin; an ATI cell marker, exhibited decreased protein expression upon pharmacological and molecular Wnt/β-catenin inhibition in cultured ATII cells, whereas CBR2 levels were stabilized. Moreover, we analyzed primary ATII cells from mice with bleomycin-induced lung injury, a model exhibiting activated Wnt/β-catenin signaling in vivo. We observed reduced CBR2 significantly correlating with surfactant protein C (SFTPC, whereas ENO1 and PDIA3 along with T1α were increased in injured ATII cells. Finally, siRNA-mediated knockdown of ENO1, as well as PDIA3, in primary ATII cells led to reduced T1α expression, indicating diminished cell trans-differentiation. Our data thus identified proteins involved in ATII-to-ATI cell trans-differentiation and suggest a Wnt/β-catenin-driven functional role of ENO1 and PDIA3 in alveolar epithelial cell plasticity in lung injury and repair.

  9. Mammary alveolar epithelial cells convert to brown adipocytes in post-lactating mice

    DEFF Research Database (Denmark)

    Giordano, Antonio; Perugini, Jessica; Kristensen, David Møbjerg

    2017-01-01

    During pregnancy and lactation, subcutaneous white adipocytes in the mouse mammary gland transdifferentiate reversibly to milk-secreting epithelial cells. In this study, we demonstrate by transmission electron microscopy that in the post-lactating mammary gland interscapular multilocular adipocyt...... organ plasticity...

  10. Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing.

    Science.gov (United States)

    Crosby, Lynn M; Luellen, Charlean; Zhang, Zhihong; Tague, Larry L; Sinclair, Scott E; Waters, Christopher M

    2011-10-01

    After acute lung injury, repair of the alveolar epithelium occurs on a substrate undergoing cyclic mechanical deformation. While previous studies showed that mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the impact of cell death during repair was not determined. We examined epithelial repair during cyclic stretch (CS) in a scratch-wound model of primary rat alveolar type II (ATII) cells and found that CS altered the balance between proliferation and cell death. We measured cell migration, size, and density; intercellular gap formation; cell number, proliferation, and apoptosis; cytoskeletal organization; and focal adhesions in response to scratch wounding followed by CS for up to 24 h. Under static conditions, wounds were closed by 24 h, but repair was inhibited by CS. Wounding stimulated cell motility and proliferation, actin and vinculin redistribution, and focal adhesion formation at the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated cytoskeletal reorganization, and attenuated focal adhesion formation. CS also caused significant intercellular gap formation compared with static cells. Our results suggest that CS alters several mechanisms of epithelial repair and that an imbalance occurs between cell death and proliferation that must be overcome to restore the epithelial barrier.

  11. Cigarette smoke-induced alveolar epithelial-mesenchymal transition is mediated by Rac1 activation.

    Science.gov (United States)

    Shen, Hui-juan; Sun, Yan-hong; Zhang, Shui-juan; Jiang, Jun-xia; Dong, Xin-wei; Jia, Yong-liang; Shen, Jian; Guan, Yan; Zhang, Lin-hui; Li, Fen-fen; Lin, Xi-xi; Wu, Xi-mei; Xie, Qiang-min; Yan, Xiao-feng

    2014-06-01

    Epithelial-mesenchymal transition (EMT) is the major pathophysiological process in lung fibrosis observed in chronic obstructive pulmonary disease (COPD) and lung cancer. Smoking is a risk factor for developing EMT, yet the mechanism remains largely unknown. In this study, we investigated the role of Rac1 in cigarette smoke (CS) induced EMT. EMT was induced in mice and pulmonary epithelial cells by exposure of CS and cigarette smoke extract (CSE) respectively. Treatment of pulmonary epithelial cells with CSE elevated Rac1 expression associated with increased TGF-β1 release. Blocking TGF-β pathway restrained CSE-induced changes in EMT-related markers. Pharmacological inhibition or knockdown of Rac1 decreased the CSE exposure induced TGF-β1 release and ameliorated CSE-induced EMT. In CS-exposed mice, pharmacological inhibition of Rac1 reduced TGF-β1 release and prevented aberrations in expression of EMT markers, suggesting that Rac1 is a critical signaling molecule for induction of CS-stimulated EMT. Furthermore, Rac1 inhibition or knockdown abrogated CSE-induced Smad2 and Akt (PKB, protein kinase B) activation in pulmonary epithelial cells. Inhibition of Smad2, PI3K (phosphatidylinositol 3-kinase) or Akt suppressed CSE-induced changes in epithelial and mesenchymal marker expression. Altogether, these data suggest that CS initiates EMT through Rac1/Smad2 and Rac1/PI3K/Akt signaling pathway. Our data provide new insights into the fundamental basis of EMT and suggest a possible new course of therapy for COPD and lung cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II

    Directory of Open Access Journals (Sweden)

    Prasse Antje

    2005-07-01

    Full Text Available Abstract The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2 and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11 in TNF-α-, IFN-γ-, and IL-1β-stimulated human alveolar epithelial cells type II (AEC-II. AEC-II constitutively expressed high level of CCL2 mRNA in vitro and in situ , and released CCL2 protein in vitro . Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-γ had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-γ, alone or in combination with IL-1β and TNF-α resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-γ>>IL-1β ≥ TNF-α. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants by in situ hybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.

  13. Environmental particulate (PM2.5 augments stiffness-induced alveolar epithelial cell mechanoactivation of transforming growth factor beta.

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    Marilyn M Dysart

    Full Text Available Dysfunctional pulmonary homeostasis and repair, including diseases such as pulmonary fibrosis (PF, chronic obstructive pulmonary disease (COPD, and tumorigenesis have been increasing over the past decade, a fact that heavily implicates environmental influences. Several investigations have suggested that in response to increased transforming growth factor--beta (TGFβ signaling, the alveolar type II (ATII epithelial cell undergoes phenotypic changes that may contribute to the complex pathobiology of PF. We have previously demonstrated that increased tissue stiffness associated with PF is a potent extracellular matrix (ECM signal for epithelial cell activation of TGFβ. The work reported here explores the relationship between tissue stiffness and exposure to environmental stimuli in the activation of TGFβ. We hypothesized that exposure of ATII cells to fine particulate matter (PM2.5 will result in enhanced cell contractility, TGFβ activation, and subsequent changes to ATII cell phenotype. ATII cells were cultured on increasingly stiff substrates with or without addition of PM2.5. Exposure to PM2.5 resulted in increased activation of TGFβ, increased cell contractility, and elongation of ATII cells. Most notably, on 8 kPa substrates, a stiffness greater than normal but less than established fibrotic lung, addition of PM2.5 resulted in increased cortical cell stiffness, enhanced actin staining and cell elongation; a result not seen in the absence of PM2.5. Our work suggests that PM2.5 exposure additionally enhances the existing interaction between ECM stiffness and TGFβ that has been previously reported. Furthermore, we show that this additional enhancement is likely a consequence of intracellular reactive oxygen species (ROS leading to increased TGFβ signaling events. These results highlight the importance of both the micromechanical and biochemical environment in lung disease initiation and suggest that individuals in early stages of lung

  14. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

    International Nuclear Information System (INIS)

    Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

    2007-01-01

    Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

  15. Epithelial Cell Damage Activates Bactericidal/Permeability Increasing-Protein (BPI Expression in Intestinal Epithelium

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    Arjun Balakrishnan

    2017-08-01

    Full Text Available As the first line of defense against invading pathogen, intestinal epithelium produces various antimicrobial proteins (AMP that help in clearance of pathogen. Bactericidal/permeability-increasing protein (BPI is a 55 kDa AMP that is expressed in intestinal epithelium. Dysregulation of BPI in intestinal epithelium is associated with various inflammatory diseases like Crohn’s Disease, Ulcerative colitis, and Infectious enteritis’s. In this paper, we report a direct correlation between intestinal damage and BPI expression. In Caco-2 cells, we see a significant increase in BPI levels upon membrane damage mediated by S. aureus infection and pore-forming toxins (Streptolysin and Listeriolysin. Cells detect changes in potassium level as a Danger-associated molecular pattern associated with cell damage and induce BPI expression in a p38 dependent manner. These results are further supported by in vivo findings that the BPI expression in murine intestinal epithelium is induced upon infection with bacteria which cause intestinal damage (Salmonella Typhimurium and Shigella flexneri whereas mutants that do not cause intestinal damage (STM ΔfliC and STM ΔinvC did not induce BPI expression. Our results suggest that epithelial damage associated with infection act as a signal to induce BPI expression.

  16. Asymmetric [14C]albumin transport across bullfrog alveolar epithelium

    International Nuclear Information System (INIS)

    Kim, K.J.; LeBon, T.R.; Shinbane, J.S.; Crandall, E.D.

    1985-01-01

    Bullfrog lungs were prepared as planar sheets and bathed with Ringer solution in Ussing chambers. In the presence of a constant electrical gradient (20, 0, or -20 mV) across the tissue, 14 C-labeled bovine serum albumin or inulin was instilled into the upstream reservoir and the rate of appearance of the tracer in the downstream reservoir was monitored. Two lungs from the same animal were used to determine any directional difference in tracer fluxes. An apparent permeability coefficient was estimated from a relationship between normalized downstream radioactivities and time. Results showed that the apparent permeability of albumin in the alveolar to pleural direction across the alveolar epithelial barrier is 2.3 X 10(-7) cm/s, significantly greater (P less than 0.0005) than that in the pleural to alveolar direction (5.3 X 10(-8) cm/s) when the tissue was short circuited. Permeability of inulin, on the other hand, did not show any directional dependence and averaged 3.1 X 10(-8) cm/s in both directions. There was no effect on radiotracer fluxes permeabilities of different electrical gradients across the tissue. Gel electrophoretograms and corresponding radiochromatograms suggest that the large and asymmetric isotope fluxes are not primarily due to digestion or degradation of labeled molecules. Inulin appears to traverse the alveolar epithelial barrier by simple diffusion through hydrated paracellular pathways. On the other hand, [ 14 C]albumin crosses the alveolar epithelium more rapidly than would be expected by simple diffusion. These asymmetric and large tracer fluxes suggest that a specialized mechanism is present in alveolar epithelium that may be capable of helping to remove albumin from the alveolar space

  17. Changes in the rat lung after exposure to radon and its progeny: Effects on incorporation of bromodeoxyuridine in epithelial cells and on the incidence of nuclear aberrations in Alveolar macrophages

    International Nuclear Information System (INIS)

    Taya, A.; Morgan, A.; Baker, S.T.; Humphreys, J.A.H.; Collier, C.G.; Bisson, M.

    1994-01-01

    The aim of this study was to investigate some responses of cells in the rat respiratory tract as a function of time after inhalation exposure to various levels of radon and its progeny. Rats were exposed to a constant concentration of radon and its progeny to give cumulative exposure levels of 120, 225, 440 and 990 working level months (WLM). An additional unexposed group of rats served as controls. The end points selected for investigation were (a) the incorporation of bromodeoxyuridine (BrdU) in epithelial cells of the conducting airways and of the alveolar region of the respiratory tract and (b) the incidence of alveolar macrophages with nuclear aberrations. After exposure, the incidence of epithelial cells incorporating BrdU-the labeling index-increased in all regions of the respiratory tract examined, but the increase occurred later in alveolar than in airway epithelial cells. The highest labeling index was found in bronchial epithelial cells, which probably received the highest radiation dose. After an initial induction period, the incidence of alveolar macrophages with nuclear aberrations also increased. The possibility of using the labeling index of alveolar and airway epithelial cells, and/or the incidence of nuclear aberrations in alveolar macrophages, to estimate the radiation dose to various regions of the respiratory tract after exposure of rats to radon and its progeny is discussed. 22 refs., 3 figs., 1 tab

  18. Hypoxia inducible factor 3α plays a critical role in alveolarization and distal epithelial cell differentiation during mouse lung development.

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    Yadi Huang

    Full Text Available Lung development occurs under relative hypoxia and the most important oxygen-sensitive response pathway is driven by Hypoxia Inducible Factors (HIF. HIFs are heterodimeric transcription factors of an oxygen-sensitive subunit, HIFα, and a constitutively expressed subunit, HIF1β. HIF1α and HIF2α, encoded by two separate genes, contribute to the activation of hypoxia inducible genes. A third HIFα gene, HIF3α, is subject to alternative promoter usage and splicing, leading to three major isoforms, HIF3α, NEPAS and IPAS. HIF3α gene products add to the complexity of the hypoxia response as they function as dominant negative inhibitors (IPAS or weak transcriptional activators (HIF3α/NEPAS. Previously, we and others have shown the importance of the Hif1α and Hif2α factors in lung development, and here we investigated the role of Hif3α during pulmonary development. Therefore, HIF3α was conditionally expressed in airway epithelial cells during gestation and although HIF3α transgenic mice were born alive and appeared normal, their lungs showed clear abnormalities, including a post-pseudoglandular branching defect and a decreased number of alveoli. The HIF3α expressing lungs displayed reduced numbers of Clara cells, alveolar epithelial type I and type II cells. As a result of HIF3α expression, the level of Hif2α was reduced, but that of Hif1α was not affected. Two regulatory genes, Rarβ, involved in alveologenesis, and Foxp2, a transcriptional repressor of the Clara cell specific Ccsp gene, were significantly upregulated in the HIF3α expressing lungs. In addition, aberrant basal cells were observed distally as determined by the expression of Sox2 and p63. We show that Hif3α binds a conserved HRE site in the Sox2 promoter and weakly transactivated a reporter construct containing the Sox2 promoter region. Moreover, Hif3α affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel

  19. Evaluation of the concentration of marbofloxacin in alveolar macrophages and pulmonary epithelial lining fluid after administration in dogs.

    Science.gov (United States)

    Boothe, Harry W; Jones, Sarah A; Wilkie, W Scott; Boeckh, Albert; Stenstrom, Kristol K; Boothe, Dawn M

    2005-10-01

    To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs. 12 adult mixed-breed and purebred hounds. 10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence. Mean +/- SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 +/- 0.52 microg/mL and 1.81 +/- 0.21 microg/mL, respectively. Mean +/- SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 +/- 24.61 microg/mL) was significantly greater than that in plasma (1.81 +/- 0.21 microg/mL) and ELF (0.82 +/- 0.34 microg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs. Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration.

  20. Characterisation of cellular adhesion reinforcement by multiple bond force spectroscopy in alveolar epithelial cells.

    Science.gov (United States)

    Nguyen, Ngoc-Minh; Angely, Christelle; Andre Dias, Sofia; Planus, Emmanuelle; Filoche, Marcel; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2017-07-01

    Integrin-mediated adhesion is a key process by which cells physically connect with their environment, and express sensitivity and adaptation through mechanotransduction. A critical step of cell adhesion is the formation of the first bonds which individually generate weak contacts (∼tens pN) but can sustain thousand times higher forces (∼tens nN) when associated. We propose an experimental validation by multiple bond force spectroscopy (MFS) of a stochastic model predicting adhesion reinforcement permitted by non-cooperative, multiple bonds on which force is homogeneously distributed (called parallel bond configuration). To do so, spherical probes (diameter: 6.6 μm), specifically coated by RGD-peptide to bind integrins, are used to statically indent and homogenously stretch the multiple bonds created for short contact times (2 s) between the bead and the surface of epithelial cells (A549). Using different separation speeds (v = 2, 5, 10 μm/s) and measuring cellular Young's modulus as well as the local stiffness preceding local rupture events, we obtain cell-by-cell the effective loading rates both at the global cell level and at the local level of individual constitutive bonds. Local rupture forces are in the range: f*=60-115 pN , whereas global rupture (detachment) forces reach F*=0.8-1.7 nN . Global and local rupture forces both exhibit linear dependencies with the effective loading rate, the slopes of these two linear relationships providing an estimate of the number of independent integrin bonds constituting the tested multiple bond structure (∼12). The MFS method enables to validate the reinforcement of integrin-mediated adhesion induced by the multiple bond configuration in which force is homogeneously distributed amongst parallel bonds. Local rupture events observed in the course of a spectroscopy manoeuver (MFS) lead to rupture force values considered in the literature as single-integrin bonds. Adhesion reinforcement permitted by the parallel

  1. Development of a lung slice preparation for recording ion channel activity in alveolar epithelial type I cells

    Directory of Open Access Journals (Sweden)

    Crandall Edward D

    2005-04-01

    Full Text Available Abstract Background Lung fluid balance in the healthy lung is dependent upon finely regulated vectorial transport of ions across the alveolar epithelium. Classically, the cellular locus of the major ion transport processes has been widely accepted to be the alveolar type II cell. Although evidence is now emerging to suggest that the alveolar type I cell might significantly contribute to the overall ion and fluid homeostasis of the lung, direct assessment of functional ion channels in type I cells has remained elusive. Methods Here we describe a development of a lung slice preparation that has allowed positive identification of alveolar type I cells within an intact and viable alveolar epithelium using living cell immunohistochemistry. Results This technique has allowed, for the first time, single ion channels of identified alveolar type I cells to be recorded using the cell-attached configuration of the patch-clamp technique. Conclusion This exciting new development should facilitate the ascription of function to alveolar type I cells and allow us to integrate this cell type into the general model of alveolar ion and fluid balance in health and disease.

  2. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells

    International Nuclear Information System (INIS)

    Artursson, P.; Karlsson, J.

    1991-01-01

    Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10 - 8 to 5 x 10 - 5 cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10 - 6 cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10 - 6 cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10 - 7 cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption

  3. Chronic air-flow limitation does not increase respiratory epithelial permeability assessed by aerosolized solute, but smoking does

    International Nuclear Information System (INIS)

    Huchon, G.J.; Russell, J.A.; Barritault, L.G.; Lipavsky, A.; Murray, J.F.

    1984-01-01

    To determine the separate influences of smoking and severe air-flow limitation on aerosol deposition and respiratory epithelial permeability, we studied 26 normal nonsmokers, 12 smokers without airway obstruction, 12 nonsmokers with chronic obstructive pulmonary disease (COPD), and 11 smokers with COPD. We aerosolized 99mTc-labeled diethylene triamine pentaacetic acid to particles approximately 1 micron activity median aerodynamic diameter. Levels of radioactivity were plotted semilogarithmically against time to calculate clearance as percent per minute. The distribution of radioactivity was homogeneous in control subjects and in smokers, but patchy in both groups with COPD. No difference was found between clearances of the control group (1.18 +/- 0.31% min-1), and nonsmoker COPD group (1.37 +/- 0.82% min-1), whereas values in smokers without COPD (4.00 +/- 1.70% min-1) and smokers with COPD (3.62 +/- 2.88% min-1) were significantly greater than in both nonsmoking groups. We conclude that (1) small particles appear to deposit peripherally, even with severe COPD; (2) respiratory epithelial permeability is normal in nonsmokers with COPD; (3) smoking increases permeability by a mechanism unrelated to air-flow limitation

  4. Quantitative Analysis of Proteome Modulations in Alveolar Epithelial Type II Cells in Response to Pulmonary Aspergillus fumigatus Infection.

    Science.gov (United States)

    Seddigh, Pegah; Bracht, Thilo; Molinier-Frenkel, Válerie; Castellano, Flavia; Kniemeyer, Olaf; Schuster, Marc; Weski, Juliane; Hasenberg, Anja; Kraus, Andreas; Poschet, Gernot; Hager, Thomas; Theegarten, Dirk; Opitz, Christiane A; Brakhage, Axel A; Sitek, Barbara; Hasenberg, Mike; Gunzer, Matthias

    2017-12-01

    The ubiquitous mold Aspergillus fumigatus threatens immunosuppressed patients as inducer of lethal invasive aspergillosis. A. fumigatus conidia are airborne and reach the alveoli, where they encounter alveolar epithelial cells (AEC). Previous studies reported the importance of the surfactant-producing AEC II during A. fumigatus infection via in vitro experiments using cell lines. We established a negative isolation protocol yielding untouched primary murine AEC II with a purity >90%, allowing ex vivo analyses of the cells, which encountered the mold in vivo By label-free proteome analysis of AEC II isolated from mice 24h after A. fumigatus or mock infection we quantified 2256 proteins and found 154 proteins to be significantly differentially abundant between both groups (ANOVA p value ≤ 0.01, ratio of means ≥1.5 or ≤0.67, quantified with ≥2 peptides). Most of these proteins were higher abundant in the infected condition and reflected a comprehensive activation of AEC II on interaction with A. fumigatus This was especially represented by proteins related to oxidative phosphorylation, hence energy production. However, the most strongly induced protein was the l-amino acid oxidase (LAAO) Interleukin 4 induced 1 (IL4I1) with a 42.9 fold higher abundance (ANOVA p value 2.91 -10 ). IL4I1 has previously been found in B cells, macrophages, dendritic cells and rare neurons. Increased IL4I1 abundance in AEC II was confirmed by qPCR, Western blot and immunohistology. Furthermore, A. fumigatus infected lungs showed high levels of IL4I1 metabolic products. Importantly, higher IL4I1 abundance was also confirmed in lung tissue from human aspergilloma. Because LAAO are key enzymes for bactericidal product generation, AEC II might actively participate in pathogen defense. We provide insights into proteome changes of primary AEC II thereby opening new avenues to analyze the molecular changes of this central lung cell on infectious threats. Data are available via Proteome

  5. Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage.

    Science.gov (United States)

    Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P; Morales-Nebreda, Luisa; Cheng, Yuan; Hogan, Erin; Yeldandi, Anjana; Chi, Monica; Piseaux, Raul; Ridge, Karen; Michael Hart, C; Chandel, Navdeep; Scott Budinger, G R; Kamp, David W

    2016-12-01

    Alveolar epithelial cell (AEC) injury and mitochondrial dysfunction are important in the development of lung fibrosis. Our group has shown that in the asbestos exposed lung, the generation of mitochondrial reactive oxygen species (ROS) in AEC mediate mitochondrial DNA (mtDNA) damage and apoptosis which are necessary for lung fibrosis. These data suggest that mitochondrial-targeted antioxidants should ameliorate asbestos-induced lung. To determine whether transgenic mice that express mitochondrial-targeted catalase (MCAT) have reduced lung fibrosis following exposure to asbestos or bleomycin and, if so, whether this occurs in association with reduced AEC mtDNA damage and apoptosis. Crocidolite asbestos (100µg/50µL), TiO 2 (negative control), bleomycin (0.025 units/50µL), or PBS was instilled intratracheally in 8-10 week-old wild-type (WT - C57Bl/6J) or MCAT mice. The lungs were harvested at 21d. Lung fibrosis was quantified by collagen levels (Sircol) and lung fibrosis scores. AEC apoptosis was assessed by cleaved caspase-3 (CC-3)/Surfactant protein C (SFTPC) immunohistochemistry (IHC) and semi-quantitative analysis. AEC (primary AT2 cells from WT and MCAT mice and MLE-12 cells) mtDNA damage was assessed by a quantitative PCR-based assay, apoptosis was assessed by DNA fragmentation, and ROS production was assessed by a Mito-Sox assay. Compared to WT, crocidolite-exposed MCAT mice exhibit reduced pulmonary fibrosis as measured by lung collagen levels and lung fibrosis score. The protective effects in MCAT mice were accompanied by reduced AEC mtDNA damage and apoptosis. Similar findings were noted following bleomycin exposure. Euk-134, a mitochondrial SOD/catalase mimetic, attenuated MLE-12 cell DNA damage and apoptosis. Finally, compared to WT, asbestos-induced MCAT AT2 cell ROS production was reduced. Our finding that MCAT mice have reduced pulmonary fibrosis, AEC mtDNA damage and apoptosis following exposure to asbestos or bleomycin suggests an important role

  6. Exposure to Bordetella pertussis adenylate cyclase toxin affects integrin-mediated adhesion and mechanics in alveolar epithelial cells.

    Science.gov (United States)

    Angely, Christelle; Nguyen, Ngoc-Minh; Andre Dias, Sofia; Planus, Emmanuelle; Pelle, Gabriel; Louis, Bruno; Filoche, Marcel; Chenal, Alexandre; Ladant, Daniel; Isabey, Daniel

    2017-08-01

    The adenylate cyclase (CyaA) toxin is a major virulent factor of Bordetella pertussis, the causative agent of whooping cough. CyaA toxin is able to invade eukaryotic cells where it produces high levels of cyclic adenosine monophosphate (cAMP) affecting cellular physiology. Whether CyaA toxin can modulate cell matrix adhesion and mechanics of infected cells remains largely unknown. In this study, we use a recently proposed multiple bond force spectroscopy (MFS) with an atomic force microscope to assess the early phase of cell adhesion (maximal detachment and local rupture forces) and cell rigidity (Young's modulus) in alveolar epithelial cells (A549) for toxin exposure 95%) at CyaA concentration of 0.5 nM, but a significant effect (≈81%) at 10 nM. MFS performed on A549 for three different concentrations (0.5, 5 and 10 nM) demonstrates that CyaA toxin significantly affects both cell adhesion (detachment forces are decreased) and cell mechanics (Young's modulus is increased). CyaA toxin (at 0.5 nM) assessed at three indentation/retraction speeds (2, 5 and 10 μm/s) significantly affects global detachment forces, local rupture events and Young modulus compared with control conditions, while an enzymatically inactive variant CyaAE5 has no effect. These results reveal the loading rate dependence of the multiple bonds newly formed between the cell and integrin-specific coated probe as well as the individual bond kinetics which are only slightly affected by the patho-physiological dose of CyaA toxin. Finally, theory of multiple bond force rupture enables us to deduce the bond number N which is reduced by a factor of 2 upon CyaA exposure (N ≈ 6 versus N ≈ 12 in control conditions). MFS measurements demonstrate that adhesion and mechanical properties of A549 are deeply affected by exposure to the CyaA toxin but not to an enzymatically inactive variant. This indicates that the alteration of cell mechanics triggered by CyaA is a consequence of the increase in

  7. Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects.

    Science.gov (United States)

    Gotfried, Mark H; Horn, Karolyn; Garrity-Ryan, Lynne; Villano, Stephen; Tzanis, Evan; Chitra, Surya; Manley, Amy; Tanaka, S Ken; Rodvold, Keith A

    2017-09-01

    The steady-state concentrations of omadacycline and tigecycline in the plasma, epithelial lining fluid (ELF), and alveolar cells (AC) of 58 healthy adult subjects were obtained. Subjects were administered either omadacycline at 100 mg intravenously (i.v.) every 12 h for two doses followed by 100 mg i.v. every 24 h for three doses or tigecycline at an initial dose of 100 mg i.v. followed by 50 mg i.v. every 12 h for six doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject following the start of the fifth dose of omadacycline at 0.5, 1, 2, 4, 8, 12, or 24 h and after the start of the seventh dose of tigecycline at 2, 4, 6, or 12 h. The value of the area under the concentration-time curve (AUC) from time zero to 24 h postdosing (AUC 0-24 ) (based on mean concentrations) in ELF and the ratio of the ELF to total plasma omadacycline concentration based on AUC 0-24 values were 17.23 mg · h/liter and 1.47, respectively. The AUC 0-24 value in AC was 302.46 mg · h/liter, and the ratio of the AC to total plasma omadacycline concentration was 25.8. In comparison, the values of the AUC from time zero to 12 h postdosing (AUC 0-12 ) based on the mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50 mg · h/liter, respectively. The ratio of the ELF and AC to total plasma concentrations of tigecycline based on AUC 0-12 values were 1.71 and 20.8, respectively. The pharmacokinetic advantages of higher and sustained concentrations of omadacycline compared to those of tigecycline in plasma, ELF, and AC suggest that omadacycline is a promising antibacterial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. Copyright © 2017 Gotfried et al.

  8. Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jie Chen

    2015-11-01

    Full Text Available Background/Aims: Mesenchymal stem cell (MSC based therapies may be useful for treating acute respiratory distress syndrome (ARDS, but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. Methods: Human alveolar epithelial cells (AEC and primary human small airway epithelial cells (SAEC were subjected to lipopolysaccharide (LPS with or without the presence of hUC-MSC-conditioned medium (CM. Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC. Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry. Results: MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM. Conclusion: Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK.

  9. Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved.

    Science.gov (United States)

    Cao, Huifang; Feng, Ying; Ning, Yunye; Zhang, Zinan; Li, Weihao; Li, Qiang

    2015-01-01

    Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. As yet, no specific treatment is available for HALI. The present study aims to investigate the effects of edaravone on hyperoxia-induced oxidative injury and the underlying mechanism. We treated rats and human pulmonary alveolar epithelial cells with hyperoxia and different concentration of edaravone, then examined the effects of edaravone on cell viability, cell injury and two oxidative products. The roles of heme oxygenase-1 (HO-1) and PI3K/Akt pathway were explored using Western blot and corresponding inhibitors. The results showed that edaravone reduced lung biochemical alterations induced by hyperoxia and mortality of rats, dose-dependently alleviated cell mortality, cell injury, and peroxidation of cellular lipid and DNA oxidative damage. It upregulated cellular HO-1 expression and activity, which was reversed by PI3K/Akt pathway inhibition. The administration of zinc protoporphyrin-IX, a HO-1 inhibitor, and LY249002, a PI3K/Akt pathway inhibitor, abolished the protective effects of edaravone in cells. This study indicates that edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia-induced injury and the antioxidant effect may be related to upregulation of HO-1, which is regulated by PI3K/Akt pathway.

  10. Blockage of glycolysis by targeting PFKFB3 alleviates sepsis-related acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells.

    Science.gov (United States)

    Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua

    2017-09-16

    Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP. The mice treated with the 3PO ameliorated the survival rate, histopathological changes, lung inflammation, lactate increased and lung apoptosis of mice with CLP-induced sepsis. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) resulted in cell apoptosis, inflammatory cytokine production, enhanced glycolytic flux and reactive oxygen species (ROS) increased. While these changes were attenuated by 3PO treatment. Sequentially, treatment of A549 cells with lactate caused cell apoptosis and enhancement of ROS. Pretreatment with N-acetylcysteine (NAC) significantly lowered LPS and lactate-induced the generation of ROS and cell apoptosis in A549 cells. Therefore, these results indicate that anaerobic glycolysis may be an important contributor in cell apoptosis of sepsis-related ALI. Moreover, LPS specifically induces apoptotic insults to A549 cell through lactate-mediated enhancement of ROS. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Cell-permeable intrinsic cellular inhibitors of apoptosis protect and rescue intestinal epithelial cells from radiation-induced cell death

    International Nuclear Information System (INIS)

    Matsuzaki-Horibuchi, Shiori; Yasuda, Takeshi; Sakaguchi, Nagako; Yamaguchi, Yoshihiro; Akashi, Makoto

    2015-01-01

    One of the important mechanisms for gastrointestinal (GI) injury following high-dose radiation exposure is apoptosis of epithelial cells. X-linked inhibitor of apoptosis (XIAP) and cellular IAP2 (cIAP2) are intrinsic cellular inhibitors of apoptosis. In order to study the effects of exogenously added IAPs on apoptosis in intestinal epithelial cells, we constructed bacterial expression plasmids containing genes of XIAP (full-length, BIR2 domain and BIR3-RING domain with and without mutations of auto-ubiquitylation sites) and cIAP2 proteins fused to a protein-transduction domain (PTD) derived from HIV-1 Tat protein (TAT) and purified these cell-permeable recombinant proteins. When the TAT-conjugated IAPs were added to rat intestinal epithelial cells IEC6, these proteins were effectively delivered into the cells and inhibited apoptosis, even when added after irradiation. Our results suggest that PTD-mediated delivery of IAPs may have clinical potential, not only for radioprotection but also for rescuing the GI system from radiation injuries. (author)

  12. Water permeability of Na+-K+-2Cl- cotransporters in mammalian epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Herrera-Perez, José Jaime; Bundgaard, Magnus

    2005-01-01

    Water transport properties of the Na+-K+-2Cl- cotransporter (NKCC) were studied in cultures of pigmented epithelial cells (PE) from the ciliary body of the eye. Here, the membrane that faces upwards contains NKCCs and can be subjected to rapid changes in bathing solution composition and osmolarity...

  13. Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model.

    Science.gov (United States)

    Sisler, Jennifer D; Pirela, Sandra V; Friend, Sherri; Farcas, Mariana; Schwegler-Berry, Diane; Shvedova, Anna; Castranova, Vincent; Demokritou, Philip; Qian, Yong

    2015-01-01

    The printer is one of the most common office equipment. Recently, it was reported that toner formulations for printing equipment constitute nano-enabled products (NEPs) and contain engineered nanomaterials (ENMs) that become airborne during printing. To date, insufficient research has been performed to understand the potential toxicological properties of printer-emitted particles (PEPs) with several studies using bulk toner particles as test particles. These studies demonstrated the ability of toner particles to cause chronic inflammation and fibrosis in animal models. However, the toxicological implications of inhalation exposures to ENMs emitted from laser printing equipment remain largely unknown. The present study investigates the toxicological effects of PEPs using an in vitro alveolar-capillary co-culture model with Human Small Airway Epithelial Cells (SAEC) and Human Microvascular Endothelial Cells (HMVEC). Our data demonstrate that direct exposure of SAEC to low concentrations of PEPs (0.5 and 1.0 µg/mL) caused morphological changes of actin remodeling and gap formations within the endothelial monolayer. Furthermore, increased production of reactive oxygen species (ROS) and angiogenesis were observed in the HMVEC. Analysis of cytokine and chemokine levels demonstrates that interleukin (IL)-6 and MCP-1 may play a major role in the cellular communication observed between SAEC and HMVEC and the resultant responses in HMVEC. These data indicate that PEPs at low, non-cytotoxic exposure levels are bioactive and affect cellular responses in an alveolar-capillary co-culture model, which raises concerns for potential adverse health effects.

  14. Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway.

    Science.gov (United States)

    Wu, Dan; Liang, Mulin; Dang, Hongxing; Fang, Fang; Xu, Feng; Liu, Chengjun

    2018-01-08

    Oxidative stress is regarded as a key regulator in the pathogenesis of prolonged hyperoxia-induced lung injury, which causes injury to alveolar epithelial cells and eventually leads to development of bronchopulmonary dysplasia (BPD). Many studies have shown that hydrogen has a protective effect in a variety of cells. However, the mechanisms by which hydrogen rescues cells from damage due to oxidative stress in BPD remains to be fully elucidated. This study sought to evaluate the effects of hydrogen on hyperoxia-induced lung injury and to investigate the underlying mechanism. Primary type II alveolar epithelial cells (AECIIs) were divided into four groups: control (21% oxygen), hyperoxia (95% oxygen), hyperoxia + hydrogen, and hyperoxia + hydrogen + LY294002 (a PI3K/Akt inhibitor). Proliferation and apoptosis of AECIIs were assessed using MTS assay and flow cytometry (FCM), respectively. Gene and protein expression were detected by quantitative polymerase chain reaction (q-PCR) and western blot analysis. Stimulation with hyperoxia decreased the expression of P-Akt, P- FoxO3a, cyclinD1 and Bcl-2. Hyperoxic conditions increased levels of Bim, Bax, and Foxo3a, which induced proliferation restriction and apoptosis of AECIIs. These effects of hyperoxia were reversed with hydrogen pretreatment. Furthermore, the protective effects of hydrogen were abrogated by PI3K/Akt inhibitor LY294002. The results indicate that hydrogen protects AECIIs from hyperoxia-induced apoptosis by inhibiting apoptosis factors and promoting the expression of anti-apoptosis factors. These effects were associated with activation of the PI3K/Akt/FoxO3a pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

    Science.gov (United States)

    Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

    2017-12-01

    Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. In vivo autoradiographic demonstration of β-adrenergic binding sites in adult rat type II alveolar epithelial cells

    International Nuclear Information System (INIS)

    Smith, D.M.; Sidhu, M.K.

    1984-01-01

    Adult male rats were injected intravenously with the muscarinic binding probe 3 H-Quinuclidinyl benzilate (QNB) or the β-adrenergic probe 3 H-dihydroalprenolol (DHA). Other rats were pre-treated with an intraperitoneal injection of a 500-fold excess of L-isoproterenol prior to the DHA. Light microscopic autoradiography of 0.5 μm sections of lung from the QNB group demonstrated very little labelling even after 6 months of exposure. In constrast, trachealis smooth muscle from these animals contained substantial labelling. Autoradiographs of lung from rats injected with DHA demonstrated labelling which was well localized over alveolar septa and concentrated over the cytoplasm of type II cells. Quantitative analysis of labelling in the DHA groups indicated a significant reduction of labelling in animals treated with L-isoproterenol prior to DHA, in both the alveolar parenchyma in general and over type II cells. The results of this study provide morphologic evidence for the uptake and specific binding of β-adrenergic antagonists by the adult lung in vivo, while failing to demonstrate similar binding of a muscarinic probe. In addition, the results demonstrate specific β-adrenergic receptors on type II cells in vivo and substantiate the view of a direct effect of β-adrenergic agonists on alveolar type II cells

  17. Conjugated primary bile salts reduce permeability of endotoxin through bacteria-stimulated intestinal epithelial cells and synergize with lecithin in suppression of inflammatory cytokine production

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schaeckeler, Simone; Moser, Lydia

    2007-01-01

    : The effect of CPBS (0.5 mM and 1.5 mM), phosphatidylcholine(0.38 mM), and human bile (0.5% vol/vol) on the barrier function was assessed by the measurement of transepithelial electrical resistance, by endotoxin permeability through the intestinal epithelial cell layer, and by basolateral cytokine enzyme...

  18. c-Kit mutation reduce intestinal epithelial cell proliferation and migration, but not influence intestinal permeability stimulated by lipopolysaccharide.

    Science.gov (United States)

    Xue, Hong; Wang, Feng Yun; Kang, Qian; Tang, Xu Dong

    2018-06-20

    The proto-oncogene c-kit, as a marker of interstitial cells of Cajal (ICCs) in the gastrointestinal tract, plays an important role in the ICCs. Although limited evidences showed c-kit is present in the colonic epithelium but its roles remain unclear. In the present study, we aimed to investigate the expression, location and function of c-kit in the intestinal epithelium. Immunofluorescence, western blotting, and RT-PCR were performed to detect the expression and location of c-kit in the intestinal mucosa of WT mice. We investigated intestinal epithelial proliferation and migration in vivo by performing 5-Bromodeoxyuridine (BrdU) incorporation and Ki-67 staining in WT and Wads m/m mice. An Ussing chamber with fluorescein-isothiocyanate dextran 4000 was used to detect the transepithelial electric resistance (TER), short circuit current (ISC) and permeability across ex vivo colon segments under control and endotoxaemia conditions. We demonstrated that c-kit was located and expressed in the gut crypt compartment in WT mice, which was demonstrated in the c-kit mutant mice (Wads m/m ). In addition, both the number of proliferating cells and the percentage of the distance migrated were lower in the Wads m/m mice than those in the WT mice. Moreover, the intestinal permeability, TER and tight junction were unaltered in the Wads m/m mice under endotoxic conditions compared with those in both the control condition and the WT mice. Altogether, these observations imply that the expression of c-kit in the colonic epithelium is involved in the proliferation and permeability of the colonic epithelium. Copyright © 2018. Published by Elsevier GmbH.

  19. Connexin 26-mediated gap junctional intercellular communication suppresses paracellular permeability of human intestinal epithelial cell monolayers

    International Nuclear Information System (INIS)

    Morita, Hidekazu; Katsuno, Tatsuro; Hoshimoto, Aihiro; Hirano, Noriaki; Saito, Yasushi; Suzuki, Yasuo

    2004-01-01

    In some cell types, gap junctional intercellular communication (GJIC) is associated with tight junctions. The present study was performed to determine the roles of GJIC in regulation of the barrier function of tight junctions. Caco-2 human colonic cells were used as a monolayer model, and barrier function was monitored by measuring mannitol permeability and transepithelial electrical resistance (TER). The monolayers were chemically disrupted by treatment with oleic acid and taurocholic acid. Western blotting analyses were performed to evaluate the protein levels of connexins, which are components of gap junctional intercellular channels. Cx26 expression was detected in preconfluent Caco-2 cells, and its level increased gradually after the monolayer reached confluency. These results prompted us to examine whether overexpression of Cx26 affects barrier function. Monolayers of Caco-2 cells stably expressing Cx26 showed significantly lower mannitol permeability and higher TER than mock transfectants when the monolayers were chemically disrupted. The levels of claudin-4, an important component of tight junctions, were significantly increased in the stable Cx26 transfectant. These results suggest that Cx26-mediated GJIC may play a crucial role in enhancing the barrier function of Caco-2 cell monolayers

  20. DA-Raf-Mediated Suppression of the Ras--ERK Pathway Is Essential for TGF-β1-Induced Epithelial-Mesenchymal Transition in Alveolar Epithelial Type 2 Cells.

    Science.gov (United States)

    Watanabe-Takano, Haruko; Takano, Kazunori; Hatano, Masahiko; Tokuhisa, Takeshi; Endo, Takeshi

    2015-01-01

    Myofibroblasts play critical roles in the development of idiopathic pulmonary fibrosis by depositing components of extracellular matrix. One source of lung myofibroblasts is thought to be alveolar epithelial type 2 cells that undergo epithelial-mesenchymal transition (EMT). Rat RLE-6TN alveolar epithelial type 2 cells treated with transforming growth factor-β1 (TGF-β1) are converted into myofibroblasts through EMT. TGF-β induces both canonical Smad signaling and non-canonical signaling, including the Ras-induced ERK pathway (Raf-MEK-ERK). However, the signaling mechanisms regulating TGF-β1-induced EMT are not fully understood. Here, we show that the Ras-ERK pathway negatively regulates TGF-β1-induced EMT in RLE-6TN cells and that DA-Raf1 (DA-Raf), a splicing isoform of A-Raf and a dominant-negative antagonist of the Ras-ERK pathway, plays an essential role in EMT. Stimulation of the cells with fibroblast growth factor 2 (FGF2), which activated the ERK pathway, prominently suppressed TGF-β1-induced EMT. An inhibitor of MEK, but not an inhibitor of phosphatidylinositol 3-kinase, rescued the TGF-β1-treated cells from the suppression of EMT by FGF2. Overexpression of a constitutively active mutant of a component of the Ras-ERK pathway, i.e., H-Ras, B-Raf, or MEK1, interfered with EMT. Knockdown of DA-Raf expression with siRNAs facilitated the activity of MEK and ERK, which were only weakly and transiently activated by TGF-β1. Although DA-Raf knockdown abrogated TGF-β1-induced EMT, the abrogation of EMT was reversed by the addition of the MEK inhibitor. Furthermore, DA-Raf knockdown impaired the TGF-β1-induced nuclear translocation of Smad2, which mediates the transcription required for EMT. These results imply that intrinsic DA-Raf exerts essential functions for EMT by antagonizing the TGF-β1-induced Ras-ERK pathway in RLE-6TN cells.

  1. The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy.

    Science.gov (United States)

    Honeybourne, D; Andrews, J M; Cunningham, B; Jevons, G; Wise, R

    1999-01-01

    The concentrations of clinafloxacin were measured in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid after single 200 mg oral doses of clinafloxacin had been administered to 15 subjects who were undergoing bronchoscopy. Concentrations were measured using a microbiological assay method. Mean concentrations in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid at a mean of 1.27 h post-dose were 1.54, 2.65, 15.60 and 2.71 mg/L respectively. These site concentrations exceeded the MIC90 for common respiratory pathogens and indicate that clinafloxacin is likely to be effective in the treatment of a wide range of respiratory tract infections.

  2. Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy

    International Nuclear Information System (INIS)

    Cayir, D.; Demirel, K.; Korkmaz, M.; Koca, G.

    2011-01-01

    Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using technetium-99m-labeled diethylenetriamine pentaacetic acid (Tc-99m DTPA) aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T 1/2 ) of Tc-99m DTPA were calculated. T 1/2 of whole lung was calculated as a mean of the T 1/2 of left and right lung. The T 1/2 values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86±8.44, and 62.14±26.12 min (p=0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function. (author)

  3. Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy.

    Science.gov (United States)

    Cayir, Derya; Demirel, Koray; Korkmaz, Meliha; Koca, Gokhan

    2011-10-01

    Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T(1/2)) of Tc-99m DTPA were calculated. T(1/2) of whole lung was calculated as a mean of the T(1/2) of left and right lung. The T(1/2) values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86 ± 8.44, and 62.14 ± 26.12 min (p = 0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function.

  4. Knockout of MIMP protein in lactobacillus plantarum lost its regulation of intestinal permeability on NCM460 epithelial cells through the zonulin pathway.

    Science.gov (United States)

    Liu, Zhihua; Kang, Liang; Li, Chao; Tong, Chao; Huang, Meijin; Zhang, Xingwei; Huang, Nanqi; Moyer, Mary Pat; Qin, Huanlong; Wang, Jianping

    2014-10-03

    Previous studies indicated that the micro integral membrane protein located within the media place of the integral membrane protein of Lactobacillus plantarum CGMCC 1258 had protective effects against the intestinal epithelial injury. In our study, we mean to establish micro integral membrane protein -knockout Lactobacillus plantarum (LPKM) to investigate the change of its protective effects and verify the role of micro integral membrane protein on protection of normal intestinal barrier function. Binding assay and intestinal permeability were performed to verify the protective effects of micro integral membrane protein on intestinal permeability in vitro and in vivo. Molecular mechanism was also determined as the zonulin pathway. Clinical data were also collected for further verification of relationship between zonulin level and postoperative septicemia. LPKM got decreased inhibition of EPEC adhesion to NCM460 cells. LPKM had lower ability to alleviate the decrease of intestinal permeability induced by enteropathogenic-e.coli, and prevent enteropathogenic-e.coli -induced increase of zonulin expression. Overexpression of zonulin lowered the intestinal permeability regulated by Lactobacillus plantarum. There was a positive correlation between zonulin level and postoperative septicemia. Therefore, micro integral membrane protein could be necessary for the protective effects of Lactobacillus plantarum on intestinal barrier. MIMP might be a positive factor for Lactobacillus plantarum to protect the intestinal epithelial cells from injury, which could be related to the zonulin pathway.

  5. Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles.

    Science.gov (United States)

    Bhattacharya, Kunal; Naha, Pratap C; Naydenova, Izabela; Mintova, Svetlana; Byrne, Hugh J

    2012-12-17

    MFI-50 nanoparticles was found to accumulate over a longer period of time as compared to MFI-100 nanoparticles. The study therefore points towards the capability of the non-cytotoxic zeolite nanoparticles to induce oxidative stress resulting in short-term altered cellular metabolism up-regulation and genomic instability. Although the damage was found to be short-lived, its persistence over longer durations, or stabilization cannot be neglected. Further studies are in progress to yield a better understanding of the mechanisms for oxidative stress and resulting cascade of events leading to genetic damage in the human lung alveolar epithelial cells following exposure to zeolite nanoparticles of different sizes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Protective Effects of Hydrogen-Rich Saline Against Lipopolysaccharide-Induced Alveolar Epithelial-to-Mesenchymal Transition and Pulmonary Fibrosis.

    Science.gov (United States)

    Dong, Wen-Wen; Zhang, Yun-Qian; Zhu, Xiao-Yan; Mao, Yan-Fei; Sun, Xue-Jun; Liu, Yu-Jian; Jiang, Lai

    2017-05-19

    BACKGROUND Fibrotic change is one of the important reasons for the poor prognosis of patients with acute respiratory distress syndrome (ARDS). The present study investigated the effects of hydrogen-rich saline, a selective hydroxyl radical scavenger, on lipopolysaccharide (LPS)-induced pulmonary fibrosis. MATERIAL AND METHODS Male ICR mice were divided randomly into 5 groups: Control, LPS-treated plus vehicle treatment, and LPS-treated plus hydrogen-rich saline (2.5, 5, or 10 ml/kg) treatment. Twenty-eight days later, fibrosis was assessed by determination of collagen deposition, hydroxyproline, and type I collagen levels. Development of epithelial-to-mesenchymal transition (EMT) was identified by examining protein expressions of E-cadherin and α-smooth muscle actin (α-SMA). Transforming growth factor (TGF)-β1 content, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, catalase (CAT), and superoxide dismutase (SOD) activity were determined. RESULTS Mice exhibited increases in collagen deposition, hydroxyproline, type I collagen contents, and TGF-β1 production in lung tissues after LPS treatment. LPS-induced lung fibrosis was associated with increased expression of α-SMA, as well as decreased expression of E-cadherin. In addition, LPS treatment increased MDA levels but decreased T-AOC, CAT, and SOD activities in lung tissues, indicating that LPS induced pulmonary oxidative stress. Hydrogen-rich saline treatment at doses of 2.5, 5, or 10 ml/kg significantly attenuated LPS-induced pulmonary fibrosis. LPS-induced loss of E-cadherin in lung tissues was largely reversed, whereas the acquisition of α-SMA was dramatically decreased by hydrogen-rich saline treatment. In addition, hydrogen-rich saline treatment significantly attenuated LPS-induced oxidative stress. CONCLUSIONS Hydrogen-rich saline may protect against LPS-induced EMT and pulmonary fibrosis through suppressing oxidative stress.

  7. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies

    International Nuclear Information System (INIS)

    Becker, Susanne; Mundandhara, Sailaja; Devlin, Robert B.; Madden, Michael

    2005-01-01

    In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preference for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS

  8. Inflammatory effects induced by selected limonene oxidation products: 4-OPA, IPOH, 4-AMCH in human bronchial (16HBE14o-) and alveolar (A549) epithelial cell lines.

    Science.gov (United States)

    Lipsa, Dorelia; Leva, Paolo; Barrero-Moreno, Josefa; Coelhan, Mehmet

    2016-11-16

    Limonene, a monoterpene abundantly present in most of the consumer products (due to its pleasant citrus smell), easily undergoes ozonolysis leading to several limonene oxidation products (LOPs) such as 4-acetyl-1-methylcyclohexene (4-AMCH), 4-oxopentanal (4-OPA) and 3-isopropenyl-6-oxoheptanal (IPOH). Toxicological studies have indicated that human exposure to limonene and ozone can cause adverse airway effects. However, little attention has been paid to the potential health impact of specific LOPs, in particular of IPOH, 4-OPA and 4-AMCH. This study evaluates the cytotoxic effects of the selected LOPs on human bronchial epithelial (16HBE14o-) and alveolar epithelial (A549) cell lines by generating concentration-response curves using the neutral red uptake assay and analyzing the inflammatory response with a series of cytokines/chemokines. The cellular viability was mostly reduced by 4-OPA [IC 50 =1.6mM (A549) and 1.45mM (16HBE14o-)] when compared to IPOH [IC 50 =3.5mM (A549) and 3.4mM (16HBE14o-)] and 4-AMCH [IC 50 could not be calculated]. As a result from the inflammatory response, IPOH [50μM] induced an increase of both IL-6 and IL-8 secretion in A549 (1.5-fold change) and in 16HBE14o- (2.8- and 7-fold change respectively). 4-OPA [50μM] treatment of A549 increased IL-6 (1.4-times) and IL-8 (1.3-times) levels, while in 16HBE14o- had an opposite effect. A549 treated with 4-AMCH [50μM] elevate both IL-6 and IL-8 levels by 1.2-times, while in 16HBE14o- had an opposite effect. Based on our results, lung cellular injury characterized by inflammatory cytokine release was observed for both cell lines treated with the selected chemicals at concentrations that did not affect their cellular viability. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  9. Andrographolide antagonizes cigarette smoke extract-induced inflammatory response and oxidative stress in human alveolar epithelial A549 cells through induction of microRNA-218.

    Science.gov (United States)

    Li, Ying-jie; Yu, Chang-hai; Li, Jing-bo; Wu, Xi-ya

    2013-12-01

    Andrographolide is a major bioactive labdane diterpenoid isolated from Andrographis paniculata and has protective effects against cigarette smoke (CS)-induced lung injury. This study was done to determine whether such protective effects were mediated through modulation of microRNA (miR)-218 expression. Therefore, we exposed human alveolar epithelial A549 cells to cigarette smoke extract (CSE) with or without andrographolide pretreatment and measured the level of glutathione, nuclear factor-kappaB (NF-κB) activation, proinflammatory cytokine production, and miR-218 expression. We found that andrographolide pretreatment significantly restored the glutathione level in CSE-exposed A549 cells, coupled with reduced inhibitor κB (IκB)-α phosphorylation and p65 nuclear translocation and interleukin (IL)-8 and IL-6 secretion. The miR-218 expression was significantly upregulated by andrographolide pretreatment. To determine the biological role of miR-218, we overexpressed and downregulated its expression using miR-218 mimic and anti-miR-218 inhibitor, respectively. We observed that miR-218 overexpression led to a marked reduction in IκB-α phosphorylation, p65 nuclear accumulation, and NF-κB-dependent transcriptional activity in CSE-treated A549 cells. In contrast, miR-218 silencing enhanced IκB-α phosphorylation and p65 nuclear accumulation in cells with andrographolide pretreatment and reversed andrographolide-mediated reduction of IL-6 and IL-8 production. In addition, depletion of miR-218 significantly reversed the upregulation of glutathione levels in A549 cells by andrographolide. Taken together, our results demonstrate that andrographolide mitigates CSE-induced inflammatory response in A549 cells, largely through inhibition of NF-κB activation via upregulation of miR-218, and thus has preventive benefits in CS-induced inflammatory lung diseases.

  10. Alveolar macrophage-epithelial cell interaction following exposure to atmospheric particles induces the release of mediators involved in monocyte mobilization and recruitment

    Directory of Open Access Journals (Sweden)

    Mukae Hiroshi

    2005-08-01

    Full Text Available Abstract Background Studies from our laboratory have shown that human alveolar macrophages (AM and bronchial epithelial cells (HBEC exposed to ambient particles (PM10 in vitro increase their production of inflammatory mediators and that supernatants from PM10-exposed cells shorten the transit time of monocytes through the bone marrow and promote their release into the circulation. Methods The present study concerns co-culture of AM and HBEC exposed to PM10 (EHC-93 and the production of mediators involved in monocyte kinetics measured at both the mRNA and protein levels. The experiments were also designed to determine the role of the adhesive interaction between these cells via the intercellular adhesion molecule (ICAM-1 in the production of these mediators. Results AM/HBEC co-cultures exposed to 100 μg/ml of PM10 for 2 or 24 h increased their levels of granulocyte-macrophage colony-stimulating factor (GM-CSF, M-CSF, macrophage inflammatory protein (MIP-1β, monocyte chemotactic protein (MCP-1, interleukin (IL-6 and ICAM-1 mRNA, compared to exposed AM or HBEC mono-cultures, or control non-exposed co-cultures. The levels of GM-CSF, M-CSF, MIP-1β and IL-6 increased in co-cultured supernatants collected after 24 h exposure compared to control cells (p 10-induced increase in co-culture mRNA expression. Conclusion We conclude that an ICAM-1 independent interaction between AM and HBEC, lung cells that process inhaled particles, increases the production and release of mediators that enhance bone marrow turnover of monocytes and their recruitment into tissues. We speculate that this interaction amplifies PM10-induced lung inflammation and contributes to both the pulmonary and systemic morbidity associated with exposure to air pollution.

  11. Non-toxic engineered carbon nanodiamond concentrations induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells.

    Science.gov (United States)

    Fresta, Claudia G; Chakraborty, Aishik; Wijesinghe, Manjula B; Amorini, Angela M; Lazzarino, Giacomo; Lazzarino, Giuseppe; Tavazzi, Barbara; Lunte, Susan M; Caraci, Filippo; Dhar, Prajnaparamita; Caruso, Giuseppe

    2018-02-14

    Engineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism. Particularly, we initially measured decrease in cell viability as a function of increasing ECNs doses, finding similar cytotoxic ECN effects in the two cell lines. Subsequently, using apparently non-cytotoxic ECN concentrations (2 µg/mL causing decrease in cell number < 5%) we determined NO and ROS production, and measured the concentrations of compounds related to energy metabolism, mitochondrial functions, oxido-reductive reactions, and antioxidant defences. We found that in both cell lines non-cytotoxic ECN concentrations increased NO and ROS production with sustained oxidative/nitrosative stress, and caused energy metabolism imbalance (decrease in high energy phosphates and nicotinic coenzymes) and mitochondrial malfunctioning (decrease in ATP/ADP ratio).These results underline the importance to deeply investigate the molecular and biochemical changes occurring upon the interaction of ECNs (and nanoparticles in general) with living cells, even at apparently non-toxic concentration. Since the use of ECNs in biomedical field is attracting increasing attention the complete evaluation of their biosafety, toxicity and/or possible side effects both in vitro and in vivo is mandatory before these highly promising tools might find the correct application.

  12. Pneumoproteins as a lung-specific biomarker of alveolar permeability in conventional on-pump coronary artery bypass graft surgery vs mini-extracorporeal circuit - A pilot study

    NARCIS (Netherlands)

    van Boven, WJP; Gerritsen, WBM; Zanen, P; Grutters, JC; van Dongen, HPA; Bernard, A; Aarts, LPHJ

    Background: Despite improvements of the heart-lung machine (HLM), oxidative stress and subsequent damage to the alveolar capillary membrane still occur after conventional on-pump coronary artery bypass graft (CCABG) surgery. In an attempt to further improve the conventional HLM, a

  13. Sphingosine 1-phosphate-induced ICAM-1 expression via NADPH oxidase/ROS-dependent NF-kappaB cascade on human pulmonary alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Chin-Chung eLin

    2016-03-01

    Full Text Available The intercellular adhesion molecule-1 (ICAM-1 expression is frequently correlated with the lung inflammation. A bioactive sphingolipid metabolite, sphingosine-1-phosphate (S1P, was involved in inflammation through the adhesion molecules induction, and then caused lung injury. However, the transduction mechanisms of the S1P stimulation to induce ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs remain unclear. Here, we demonstrated that exposure of HPAEpiCs to S1P significantly induces ICAM-1 expression leading to increase monocyte adhesion on the surface of HPAEpiCs. These phenomena were effectively attenuated by pretreatments with series of inhibitors such as Rottlerin (PKCdelta, PF431396 (PYK2, diphenyleneiodonium chloride (DPI, apocynin (NADPH oxidase, Edaravone (ROS, and Bay11-7082 (NF-kappaB. Consistently, knockdown with siRNA transfection of PKCdelta, PYK2, p47phox, and p65 exhibited the same results. Pretreatment with both Gq-coupled receptor antagonist (GPA2A and Gi/o-coupled receptor antagonist (GPA2 also blocked S1P-induced ICAM-1 protein and mRNA expression. We observed that S1P induced PYK2 activation via a Gq-coupled receptor/PKCdelta-dependent pathway. In addition, S1P induced NADPH oxidase activation and intracellular ROS generation, which were also reduced by Rottlerin or PF431396. We demonstrated that S1P induced NF-kappaB p65 phosphorylation and translocation from the cytosol to the nucleus in HPAEpiCs, which was inhibited by Rottlerin, PF431396, APO, DPI, or Edaravone. In the in vitro study, we established that S1P induced monocyte adhesion via an ICAM-1-dependent pathway. In the in vivo study, we found that S1P induced ICAM-1 protein and mRNA levels in the lung fractions, pulmonary hematoma, and leukocyte (mainly eosinophils and neutrophils count in bronchoalveolar lavage (BAL fluid in mice via a PKCdelta/PYK2/NADPH oxidase/ROS/NF-kappaB signaling pathway. We concluded that S1P may induce lung

  14. Sphingosine 1-Phosphate-Induced ICAM-1 Expression via NADPH Oxidase/ROS-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells

    Science.gov (United States)

    Lin, Chih-Chung; Yang, Chien-Chung; Cho, Rou-Ling; Wang, Chen-Yu; Hsiao, Li-Der; Yang, Chuen-Mao

    2016-01-01

    The intercellular adhesion molecule-1 (ICAM-1) expression is frequently correlated with the lung inflammation. In lung injury, sphingosine-1-phosphate (S1P, bioactive sphingolipid metabolite), participate gene regulation of adhesion molecule in inflammation progression and aggravate tissue damage. To investigate the transduction mechanisms of the S1P in pulmonary epithelium, we demonstrated that exposure of HPAEpiCs (human pulmonary alveolar epithelial cells) to S1P significantly induces ICAM-1 expression leading to increase monocyte adhesion on the surface of HPAEpiCs. These phenomena were effectively attenuated by pretreatments with series of inhibitors such as Rottlerin (PKCδ), PF431396 (PYK2), diphenyleneiodonium chloride (DPI), apocynin (NADPH oxidase), Edaravone (ROS), and Bay11-7082 (NF-κB). Consistently, knockdown with siRNA transfection of PKCδ, PYK2, p47phox, and p65 exhibited the same results. Pretreatment with both Gq-coupled receptor antagonist (GPA2A) and Gi/o-coupled receptor antagonist (GPA2) also blocked the upregulation of ICAM-1 protein and mRNA induced by S1P. We observed that S1P induced PYK2 activation via a Gq-coupled receptor/PKCδ-dependent pathway. In addition, S1P induced NADPH oxidase activation and intracellular ROS generation, which were also reduced by Rottlerin or PF431396. We demonstrated that S1P induced NF-κB p65 phosphorylation and nuclear translocation in HPAEpiCs. Activated NF-κB was blocked by Rottlerin, PF431396, APO, DPI, or Edaravone. Besides, the results of monocyte adhesion assay indicated that S1P-induced ICAM-1 expression on HPAEpiCs can enhance the monocyte attachments. In the S1P-treated mice, we found that the levels of ICAM-1 protein and mRNA in the lung fractions, the pulmonary hematoma and leukocyte count in bronchoalveolar lavage fluid were enhanced through a PKCδ/PYK2/NADPH oxidase/ROS/NF-κB signaling pathway. We concluded that S1P-accelerated lung damage is due to the ICAM-1 induction associated with

  15. Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.

    Science.gov (United States)

    Andrews, J; Honeybourne, D; Jevons, G; Boyce, M; Wise, R; Bello, A; Gajjar, D

    2003-03-01

    A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

  16. Bulky PAH-DNA induced by exposure of a co-culture model of human alveolar macrophages and embryonic epithelial cells to atmospheric particulate pollution

    International Nuclear Information System (INIS)

    Abbas, Imane; Garcon, Guillaume; Billet, Sylvain; Shirali, Pirouz; Andre, Veronique; Le Goff, Jeremie; Sichel, Francois; Roy Saint-Georges, Francoise; Mulliez, Philippe

    2012-01-01

    Because of their deep penetration in human lungs, fine airborne particulate matter were described as mainly responsible for the deleterious effects of exposure to air pollution on health. Organic constituents are adsorbed on particles surface and, after inhalation, some (polycyclic aromatic hydrocarbons, PAHs) can be activated into reactive metabolites and can bind to DNA. The formation of bulky DNA adducts has been researched after exposure of mono-and co-cultures of alveolar macrophages (AM) and human embryonic human lung epithelial (L132), to fine air pollution particulate matter Air samples have been collected with cascade impactor and characterized: size distribution (92.15% 2 /g), inorganic (Fe, AI, Ca, Na, K, Mg, Pb, etc.) and organic compounds (PAHs, etc.). 32 P post-labeling method was applied to detect bulky DNA adducts in AM and L132, in mono-and co-cultures, 72 h after their exposure to atmospheric particles at their Lethals and Effects concentrations or (LC or CE) to 50% (i.e. MA: EC 50 = 74.63 μg/mL and L132: LC-5-0 = 75.36 μg/mL). Exposure to desorbed particles (MA: C1= 61.11 μg/mL and L132 : C2 = 61.71 μg/mL) and B[a]P (1 μM) were included. Bulky PAH-DNA adducts were detected in AM in mono-culture after exposure to total particles (Pt), to B[a]P and desorbed particles (Pd). Whatever the exposure, no DNA adduct was detected in L132 in mono-culture. These results are coherent with the enzymatic activities of cytochrome P450 l Al in AM and L132. Exposure of co-culture to Pt, or Pd induced bulky adducts to DNA in AM but not in L132. Exposure to B[a]P alone has altered the DNA of AM and L132, in co-culture. Exposure to Pt is closer to the environmental conditions, but conferred an exposure to amounts of genotoxic agents compared to studies using organic extracts. The formation of bulky DNA adducts was nevertheless observed in AM exposed to Pt, in mono- or co-culture, indicating that they were competent in terms of metabolic activation of PAHs. The

  17. Epigalloccatechin-3-gallate Inhibits Ocular Neovascularization and Vascular Permeability in Human Retinal Pigment Epithelial and Human Retinal Microvascular Endothelial Cells via Suppression of MMP-9 and VEGF Activation

    Directory of Open Access Journals (Sweden)

    Hak Sung Lee

    2014-08-01

    Full Text Available Epigalloccatechin-3-gallate (EGCG is the main polyphenol component of green tea (leaves of Camellia sinensis. EGCG is known for its antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs and vascular endothelial growth factor (VEGF play a key role in the processes of extracellular matrix (ECM remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA and tumor necrosis factor alpha (TNF-α in human retinal pigment epithelial cells (HRPECs. EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2 by inhibiting generation of reactive oxygen species (ROS. EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF-induced human retinal microvascular endothelial cells (HRMECs. Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31 on corneal neovascularization (CNV induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization.

  18. Comparative study of the effects of PM1-induced oxidative stress on autophagy and surfactant protein B and C expressions in lung alveolar type II epithelial MLE-12 cells.

    Science.gov (United States)

    Bai, Ru; Guan, Longfei; Zhang, Wei; Xu, Jinxia; Rui, Wei; Zhang, Fang; Ding, Wenjun

    2016-12-01

    There is a strong link between smaller air pollution particles and a range of serious health conditions. Thus, there is a need for understanding the impacts of airborne fine particulate matter (PM) with an aerodynamic diameter of PM1) on lung alveolar epithelial cells. In the present study, mouse lung epithelial type II cell MLE-12 cells were used to examine the intracellular oxidative responses and the surfactant protein expressions after exposure to various concentrations of PM1 collected from an urban site and a steel-factory site (referred as uPM1 and sPM1 hereafter, respectively). Physicochemical characterization of PM1 was performed by using scanning electron microscopy and transmission electron microscopy. Cytotoxicity and autophagy induced by PM1 were assessed by using comprehensive approaches after MLE-12 cells were exposed to different concentrations of PM1 for various times. Expression of surfactant proteins B and C in MLE-12 cells was determined by Western blotting. All of the tested PM1 induced cytotoxicity evidenced by significant decrease of cell viability and increase of lactate dehydrogenase (LDH) release in a time- and concentration-dependent manner in the exposed cells compared with the unexposed cells. A similar pattern of increase of intercellular reactive oxygen species (ROS) generation and decrease of superoxide dismutase (SOD) and catalase (CAT) activities was also observed. PM1-induced autophagy was evidenced by an increase in microtubule-associated protein light chain-3 (LC3) puncta, accumulation of LC3II, and increased levels of beclin1. Data from Western blotting showed significant decrease of surfactant protein B and C expressions. Relatively high concentrations of transition metals, including Fe, Cu and Mn, may be responsible for the higher toxicity of sPM1 compared with uPM1. Moreover, pretreatment with N-acetylcysteine (NAC) or Chelex (a metal chelating agent, which removes a large suite of metals from PM1) prevented the increase of

  19. Relative permeability of the endothelium and epithelium of rabbit lungs

    International Nuclear Information System (INIS)

    Effros, R.M.; Mason, G.R.; Silverman, P.; Hukkanen, J.

    1986-01-01

    Electron micrographic studies of lungs suggest that the epithelial cells are more tightly joined than the underlying endothelium, and macromolecules penetrate the endothelium more readily than the epithelium. Comparisons of epithelial and endothelial permeability to small molecules have been based upon the relative rates at which solutes traverse the alveolar-capillary barrier in fluid filled lungs and those at which they equilibrate across the capillaries in air-filled lungs. Because the former process is much slower than the latter, it has been concluded that the epithelium is less permeable to small solutes than the endothelium. However this difference may be related to inadequate access of solutes to airway surfaces. In this study, solute losses from the vascular space were compared to those from the airspace in perfused, fluid-filled rabbit lungs. 36 Cl - and 125 I - were lost from air-spaces almost twice as rapidly as 22 Na + . In contrast, the endothelium is equally permeable to 22 Na + and these anions. Loss of 3 H-mannitol from the perfusate resembled that of 22 Na + for about 30 minutes, after which diffusion of 3 H-mannitol into the tissue nearly ceased. These observations suggest that the epithelium is more permselective than the endothelium. By resisting solute and water transport, the epithelium tends to prevent alveolar flooding and confines edema to the interstitium, where it is less likely to interfere with gas exchange

  20. microRNA-4516 Contributes to Different Functions of Epithelial Permeability Barrier by Targeting Poliovirus Receptor Related Protein 1 in Enterovirus 71 and Coxsackievirus A16 Infections

    Directory of Open Access Journals (Sweden)

    Yajie Hu

    2018-04-01

    Full Text Available Enterovirus 71 (EV-A71 and coxsackievirus A16 (CV-A16 remain the predominant etiological agents of hand, foot, and mouth disease (HFMD. The clinical manifestations caused by the two viruses are obviously different. CV-A16 usually triggers a repeated infection, and airway epithelial integrity is often the potential causative factor of respiratory repeated infections. Our previous studies have demonstrated that there were some differentially expressed miRNAs involved in the regulation of adhesion function of epithelial barrier in EV-A71 and CV-A16 infections. In this study, we compared the differences between EV-A71 and CV-A16 infections on the airway epithelial barrier function in human bronchial epithelial (16HBE cells and further screened the key miRNA which leaded to the formation of these differences. Our results showed that more rapid proliferation, more serious destruction of 16HBE cells permeability, more apoptosis and disruption of intercellular adhesion-associated molecules were found in CV-A16 infection as compared to EV-A71 infection. Furthermore, we also identified that microRNA-4516 (miR-4516, which presented down-regulation in EV-A71 infection and up-regulation in CV-A16 infection was an important regulator of intercellular junctions by targeting Poliovirus receptor related protein 1(PVRL1. The expressions of PVRL1, claudin4, ZO-1 and E-cadherin in CV-A16-infected cells were significantly less than those in EV-A71-infected cells, while the expressions of these proteins were subverted when pre-treated with miR-4516-overexpression plasmid in EV-A71 infected and miR-4516-knockdown plasmid in CV-A16 infected 16HBE cells. Thus, these data suggested that the opposite expression of miR-4516 in EV-A71 and CV-A16 infections might be the initial steps leading to different epithelial impairments of 16HBE cells by destroying intercellular adhesion, which finally resulted in different outcomes of EV-A71 and CV-A16 infections.

  1. Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

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    Yanan Gao

    2017-12-01

    Full Text Available Aflatoxin M1 (AFM1 and ochratoxin A (OTA are mycotoxins commonly found in milk; however, their effects on intestinal epithelial cells have not been reported. In the present study, we show that AFM1 (0.12 and 12 μM and OTA (0.2 and 20 μM individually or collectively increased the paracellular flux of lucifer yellow and fluorescein isothiocyanate (FITC-dextrans (4 and 40 kDa and decreased transepithelial electrical resistance values in differentiated Caco-2 cells after 48 h of exposure, indicating increased epithelial permeability. Immunoblotting and immunofluorescent analysis revealed that AFM1, OTA, and their combination decreased the expression levels of tight junction (TJ proteins and disrupted their structures, namely, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1, and p44/42 mitogen-activated protein kinase (MAPK partially involved in the mycotoxins-induced disruption of intestinal barrier. The effects of a combination of AFM1 and OTA on intestinal barrier function were more significant (p < 0.05 than those of AFM1 and OTA alone, yielding additive or synergistic effects. The additive or synergistic effects of AFM1 and OTA on intestinal barrier function might affect human health, especially in children, and toxin risks should be considered.

  2. Systems-level comparison of host responses induced by pandemic and seasonal influenza A H1N1 viruses in primary human type I-like alveolar epithelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Guan Yi

    2010-10-01

    Full Text Available Abstract Background Pandemic influenza H1N1 (pdmH1N1 virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. Methods We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus. Results Overall, we found that most of the genes that induced by the pdmH1N1 were similarly regulated in response to seasonal H1N1 infection with respect to both trend and extent of gene expression. These commonly responsive genes were largely related to the interferon (IFN response. Expression of the type III IFN IL29 was more prominent than the type I IFN IFNβ and a similar pattern of expression of both IFN genes was seen in pdmH1N1 and seasonal H1N1 infection. Genes that were significantly down-regulated in response to seasonal H1N1 but not in response to pdmH1N1 included the zinc finger proteins and small nucleolar RNAs. Gene Ontology (GO and pathway over-representation analysis suggested that these genes were associated with DNA binding and transcription/translation related functions. Conclusions Both seasonal H1N1 and pdmH1N1 trigger similar host responses including IFN-based antiviral responses and cytokine responses. Unlike the avian H5N1 virus, pdmH1N1 virus does not have an intrinsic capacity for cytokine dysregulation. The differences between pdmH1N1 and seasonal H1N1 viruses

  3. The permeability characteristics and interaction of main components from Si-Ni-San in a MDCK epithelial cell monolayer model.

    Science.gov (United States)

    Chen, Ruonan; Shen, Chenlin; Xu, Qingqing; Liu, Yaru; Li, Bo; Huang, Cheng; Ma, Taotao; Meng, Xiaoming; Wu, Maomao; Li, Jun

    2017-07-26

    1. Si-Ni-San (SNS) possesses extensive therapeutic effects, however, the extent to which main components are absorbed and the mechanisms involved are controversial. 2. In this study, MDCK cell model was used to determine the permeability characteristics and interaction between the major components of Si-Ni-San, including saikosaponin a, paeoniflorin, naringin and glycyrrhizic acid. 3. The transport of the major components was concentration-dependent in both directions. Moreover, the transport of paeoniflorin, naringin and glycyrrhizic acid was significantly reduced at 4°C or in the presence of NaN3. Additionally, the efflux of paeoniflorin and naringin were apparently reduced in the presence of P-gp inhibitor verapamil. The transport of glycyrrhizic acid was clearly inhibited by the inhibitors of MRP2, indicating that MRP2 may be involved in the transport of glycyrrhizic acid. However, the results indicated that saikosaponin a was absorbed mainly by passive diffusion. Furthermore, the combined incubation of four major components had a powerful sorbefacient effect than a single drug used alone which may be regulated by tight junctions. 4. Taken together, our study provides useful information for pharmacological applications of Si-Ni-San and offers new insights into this ancient decoction for further researches, especially in drug synergism.

  4. Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to 99mTc-DTPA

    International Nuclear Information System (INIS)

    Chinet, T.; Dusser, D.; Labrune, S.; Collignon, M.A.; Chretien, J.; Huchon, G.J.

    1990-01-01

    Respiratory epithelial clearance of 99m Tc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of 113m In-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stable during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy

  5. Increased alveolar soluble Annexin V promotes lung inflammation and fibrosis

    OpenAIRE

    Buckley, S.; Shi, W.; Xu, W.; Frey, M.R.; Moats, R.; Pardo, A.; Selman, M.; Warburton, D.

    2015-01-01

    The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesized that alveolar soluble Annexin V contributes to lung fibrosis, based on the observation that human IPF BALF containing high Annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when Annexin V was depleted from the BALF.

  6. Protective effect of Ac-SDKP on alveolar epithelial cells through inhibition of EMT via TGF-β1/ROCK1 pathway in silicosis in rat

    International Nuclear Information System (INIS)

    Deng, Haijing; Xu, Hong; Zhang, Xianghong; Sun, Yue; Wang, Ruimin; Brann, Darrell; Yang, Fang

    2016-01-01

    The epithelial–mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leading to inhibition of EMT. To address this hypothesis, we first examined the effect of Ac-SDKP upon EMT using an in vivo rat silicosis model, as well as in an in vitro model of TGF-β1-induced EMT. Confocal laser scanning microscopy was used to examine colocalization of surfactant protein A (SP-A), fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA) in vivo. Western blot analysis was used to examine for changes in the protein levels of E-cadherin (E-cad) and SP-A (epithelial cell markers), vimentin (mesenchymal cell marker), α-SMA (active myofibroblast marker), and collagen I and III in both in vivo and in vitro experiments. Secondly, we utilized Western blot analysis and confocal laser scanning microscopy to examine the protein expression of TGF-β1 and ROCK1 in in vivo and in vitro studies. The results revealed that Ac-SDKP treatment prevented increases in the expression of mesenchymal markers as well as TGF-β1, ROCK1, collagen I and III. Furthermore, Ac-SDKP treatment prevented decreases in the expression of epithelial cell markers in both in vivo and in vitro experiments. Based on the results, we conclude that Ac-SDKP inhibits the transition of epithelial cell-myofibroblast in silicosis via activation of the TGF-β1/ROCK1 signaling pathway, which may serve as a novel mechanism by which it exerts its anti-fibrosis properties. - Highlights: • EMT is a critical stage during the development of silicosis fibrosis. • Ac-SDKP inhibits the EMT process in silicosis both in vivo and in vitro. • Ac-SDKP inhibits the EMT process in silicosis via TGF-β1/ROCK1 pathway.

  7. Protective effect of Ac-SDKP on alveolar epithelial cells through inhibition of EMT via TGF-β1/ROCK1 pathway in silicosis in rat

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Haijing [School of Basic Medical Sciences, North China University of Science and Technology, Tangshan (China); Xu, Hong [Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan (China); Zhang, Xianghong [Pathology Department, Hebei Medical University, Shi Jiazhuang (China); Sun, Yue; Wang, Ruimin [Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan (China); Brann, Darrell [Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912 (United States); Yang, Fang, E-mail: fangyang1978@163.com [Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan (China)

    2016-03-01

    The epithelial–mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leading to inhibition of EMT. To address this hypothesis, we first examined the effect of Ac-SDKP upon EMT using an in vivo rat silicosis model, as well as in an in vitro model of TGF-β1-induced EMT. Confocal laser scanning microscopy was used to examine colocalization of surfactant protein A (SP-A), fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA) in vivo. Western blot analysis was used to examine for changes in the protein levels of E-cadherin (E-cad) and SP-A (epithelial cell markers), vimentin (mesenchymal cell marker), α-SMA (active myofibroblast marker), and collagen I and III in both in vivo and in vitro experiments. Secondly, we utilized Western blot analysis and confocal laser scanning microscopy to examine the protein expression of TGF-β1 and ROCK1 in in vivo and in vitro studies. The results revealed that Ac-SDKP treatment prevented increases in the expression of mesenchymal markers as well as TGF-β1, ROCK1, collagen I and III. Furthermore, Ac-SDKP treatment prevented decreases in the expression of epithelial cell markers in both in vivo and in vitro experiments. Based on the results, we conclude that Ac-SDKP inhibits the transition of epithelial cell-myofibroblast in silicosis via activation of the TGF-β1/ROCK1 signaling pathway, which may serve as a novel mechanism by which it exerts its anti-fibrosis properties. - Highlights: • EMT is a critical stage during the development of silicosis fibrosis. • Ac-SDKP inhibits the EMT process in silicosis both in vivo and in vitro. • Ac-SDKP inhibits the EMT process in silicosis via TGF-β1/ROCK1 pathway.

  8. Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation.

    Science.gov (United States)

    Moazed, Farzad; Burnham, Ellen L; Vandivier, R William; O'Kane, Cecilia M; Shyamsundar, Murali; Hamid, Umar; Abbott, Jason; Thickett, David R; Matthay, Michael A; McAuley, Daniel F; Calfee, Carolyn S

    2016-12-01

    Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 μg LPS inhalation (n=30). After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 μg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1β (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men.

    Science.gov (United States)

    Andrews, J; Honeybourne, D; Ashby, J; Jevons, G; Fraise, A; Fry, P; Warrington, S; Hawser, S; Wise, R

    2007-09-01

    A validated microbiological assay was used to measure concentrations of iclaprim (AR-100) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF) after a single 1.6 mg/kg intravenous 60 min iv infusion of iclaprim. Male volunteers were randomly allocated to three nominal sampling time intervals 1-2 h (Group A), 3-4 h (Group B) and 5.5-7.0 h (Group C) after the start of the drug infusion. Mean iclaprim concentrations in plasma, BM, AM and ELF, respectively, were for Group A 0.59 mg/L (SD 0.18), 0.51 mg/kg (SD 0.17), 24.51 mg/L (SD 21.22) and 12.61 mg/L (SD 7.33); Group B 0.24 mg/L (SD 0.05), 0.35 mg/kg (SD 0.17), 7.16 mg/L (SD 1.91) and 6.38 mg/L (SD 5.17); and Group C 0.14 mg/L (SD 0.05), no detectable level in BM, 5.28 mg/L (SD 2.30) and 2.66 mg/L (SD 2.08). Iclaprim concentrations in ELF and AM exceeded the MIC(90) for penicillin-susceptible Streptococcus pneumoniae (MIC90 0.06 mg/L), penicillin-intermediate S. pneumoniae (MIC90 2 mg/L), penicillin-resistant S. pneumoniae (MIC90 4 mg/L) for 7, 7 and 4 h, respectively, and Chlamydia pneumoniae (MIC90 0.5 mg/L) for 7 h. Mean iclaprim concentrations in ELF exceeded the MIC90 for Haemophilus influenzae (MIC90 4 mg/L) and Moraxella catarrhalis (MIC90 8 mg/L) for up to 4 and 2 h, respectively; in AM the MIC90 was exceeded for up to 7 h. Furthermore, the MIC90 for methicillin-resistant Staphylococcus aureus of 0.12 mg/L was exceeded at all sites for up to 7 h. These data suggest that iclaprim reaches lung concentrations that should be effective in the treatment of community-acquired pneumonia.

  10. Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    C Lin

    Full Text Available Our previous studies showed that bovine respiratory syncytial virus (BRSV followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2 epithelial cells with H. somni concentrated culture supernatant (CCS stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2 and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo.

  11. Repopulation of denuded tracheal grafts with alveolar type II cells

    International Nuclear Information System (INIS)

    Johnson, N.F.

    1988-01-01

    Repopulation of denuded heterotopic tracheal grafts with populations of specific epithelial cell types is one approach to study the differentiation potential of various cell types. This technique has been adopted to delineate the differentiation pathways of alveolar type II cells isolated from rat lungs. Under the conditions of this experiment, the reestablished epithelial lining was alveolar-like, however, ultrastructural analysis of the cells showed them to be like Clara cells. These preliminary results suggest that the secretary cells of the lung parenchyma and terminal airways may share a common ancestry. (author)

  12. Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

    Science.gov (United States)

    Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

    2011-01-01

    Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

  13. Proteinosis alveolar pulmonar Pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    Concepción Sánchez Infante

    2011-12-01

    Full Text Available La proteinosis alveolar pulmonar es una enfermedad respiratoria crónica, caracterizada por alteración en el metabolismo del surfactante, lo que determina su acumulación anormal en el espacio alveolar. Es una enfermedad extremadamente rara. Se han reportado solamente 500 casos en la literatura. Se describió por primera vez en 1958. Se presenta un caso de proteinosis alveolar pulmonar en un lactante de 2 meses, con desnutrición proteico energética, que ingresa por dificultad respiratoria e hipoxemia, y, con imágenes radiológicas de tipo retículo-nodulillar, en vidrio deslustrado, en el cual se plantea inicialmente el diagnóstico de bronconeumonía. Ante la evolución desfavorable y no respuesta al tratamiento, se realizó un estudio para descartar enfermedades pulmonares crónicas. El paciente fallece y se confirma el diagnóstico por anatomía patológica. Se realiza una revisión del tema.The pulmonary alveolar proteinosis is a chronic respiratory disease characterized by surfactant metabolism alteration determining its abnormal accumulation in the alveolar space. It is a disease very rare and in literature only 500 cases have been reported; it was described for the first time in 1958. This is a case presentation of pulmonary alveolar proteinosis in an infant aged 2 months with energetic protein malnutrition admitted due to respiratory difficulty and hypoxemia and with radiologic images of the reticulonodulillary, in frosting glass, where initially is made the diagnosis of bronchopneumonia. In the face of unfavorable evolution and no response to treatment, a study was conducted to rule out chronic pulmonary diseases. Patient died confirming the diagnosis according to the pathologic anatomy. A review on subject is carried out.

  14. Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1β-exposed human intestinal epithelial cells.

    Science.gov (United States)

    Gentile, C; Perrone, A; Attanzio, A; Tesoriere, L; Livrea, M A

    2015-08-01

    Dietary approaches to control inflammatory bowel diseases (IBD) may include proanthocyanidin-rich foods. Our previous research showed that a hydrophilic extract from Sicilian pistachio nut (HPE) contains substantial amounts of proanthocyanidins and possesses anti-inflammatory activities. We studied the effects of HPE and of its polymeric proanthocyanidin fraction (PPF) in a cell model that simulated some conditions of IBD, consisting of interleukin (IL)-1β-stimulated Caco-2 cells. HPE was prepared by Pistacia vera L. nuts, and PPF was isolated from HPE by adsorbance chromatography. Proanthocyanidins were quantified as anthocyanidins after acidic hydrolysis. Differentiated Caco-2 cells were pre-incubated with HPE or PPF and then were exposed to IL-1β. Cell viability and parameters associated with nuclear factor-κB (NF-κB) activation were assayed. Adsorption of polymeric proanthocyanidins to the cell membrane was investigated by transepithelial electrical resistance (TEER) measurements. HPE decreased prostaglandin (PG)E2 production, IL-6 and IL-8 release, and cyclooxygenase (COX)-2 expression. HPE also inhibited the increase in paracellular permeability and reduced NF-κB activation. Polymeric proanthocyanidins, tested at a concentration comparable with their content in HPE, produced effects comparable to HPE. Finally, cell exposure to PPF increases TEER of the epithelial monolayers. Our results provide evidence that pistachio nut components inhibit inflammatory response of intestinal epithelial cells in vitro and indicate polymeric proanthocyanidins as the major bioactive nut components. The protection implies inhibition of NF-κB activation and occurs in parallel with the adsorption of polymeric proanthocyanidins to cell membrane. Our findings suggest that intake of small amounts of pistachio nut can exert beneficial effects to gastrointestinal pathophysiology.

  15. Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells.

    Science.gov (United States)

    Tesoriere, L; Attanzio, A; Allegra, M; Gentile, C; Livrea, M A

    2014-02-01

    Dietary redox-active/antioxidant phytochemicals may help control or mitigate the inflammatory response in chronic inflammatory bowel disease (IBD). In the present study, the anti-inflammatory activity of indicaxanthin (Ind), a pigment from the edible fruit of cactus pear (Opuntia ficus-indica, L.), was shown in an IBD model consisting of a human intestinal epithelial cell line (Caco-2 cells) stimulated by IL-1β, a cytokine known to play a major role in the initiation and amplification of inflammatory activity in IBD. The exposure of Caco-2 cells to IL-1β brought about the activation of NADPH oxidase (NOX-1) and the generation of reactive oxygen species (ROS) to activate intracellular signalling leading to the activation of NF-κB, with the over-expression of inflammatory enzymes and release of pro-inflammatory mediators. The co-incubation of the cells with Ind, at a nutritionally relevant concentration (5-25 μM), and IL-1β prevented the release of the pro-inflammatory cytokines IL-6 and IL-8, PGE2 and NO, the formation of ROS and the loss of thiols in a dose-dependent manner. The co-incubation of the cells with Ind and IL-1β also prevented the IL-1β-induced increase of epithelial permeability. It was also shown that the activation of NOX-1 and NF-κB was prevented by Ind and the expression of COX-2 and inducible NO synthase was reduced. The uptake of Ind in Caco-2 cell monolayers appeared to be unaffected by the inflamed state of the cells. In conclusion, our findings suggest that the dietary pigment Ind may have the potential to modulate inflammatory processes at the intestinal level.

  16. Crustal permeability

    Science.gov (United States)

    Gleeson, Tom; Ingebritsen, Steven E.

    2016-01-01

    Permeability is the primary control on fluid flow in the Earth’s crust and is key to a surprisingly wide range of geological processes, because it controls the advection of heat and solutes and the generation of anomalous pore pressures.  The practical importance of permeability – and the potential for large, dynamic changes in permeability – is highlighted by ongoing issues associated with hydraulic fracturing for hydrocarbon production (“fracking”), enhanced geothermal systems, and geologic carbon sequestration.  Although there are thousands of research papers on crustal permeability, this is the first book-length treatment.  This book bridges the historical dichotomy between the hydrogeologic perspective of permeability as a static material property and the perspective of other Earth scientists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions. 

  17. Notional Permeability

    NARCIS (Netherlands)

    Kik, R.; Van den Bos, J.P.; Maertens, J.; Verhagen, H.J.; Van der Meer, J.W.

    2012-01-01

    Different layer design of a rock slope and under layers has a large effect on the strengths on the rock slope itself. In the stability formula developed of VAN DER MEER [1988] this effect is represented by the term Notional Permeability with symbol P. A more open, or permeable, structure underneath

  18. The axonal guidance cue semaphorin 3C contributes to alveolar growth and repair.

    Directory of Open Access Journals (Sweden)

    Arul Vadivel

    Full Text Available Lung diseases characterized by alveolar damage such as bronchopulmonary dysplasia (BPD in premature infants and emphysema lack efficient treatments. Understanding the mechanisms contributing to normal and impaired alveolar growth and repair may identify new therapeutic targets for these lung diseases. Axonal guidance cues are molecules that guide the outgrowth of axons. Amongst these axonal guidance cues, members of the Semaphorin family, in particular Semaphorin 3C (Sema3C, contribute to early lung branching morphogenesis. The role of Sema3C during alveolar growth and repair is unknown. We hypothesized that Sema3C promotes alveolar development and repair. In vivo Sema3C knock down using intranasal siRNA during the postnatal stage of alveolar development in rats caused significant air space enlargement reminiscent of BPD. Sema3C knock down was associated with increased TLR3 expression and lung inflammatory cells influx. In a model of O2-induced arrested alveolar growth in newborn rats mimicking BPD, air space enlargement was associated with decreased lung Sema3C mRNA expression. In vitro, Sema3C treatment preserved alveolar epithelial cell viability in hyperoxia and accelerated alveolar epithelial cell wound healing. Sema3C preserved lung microvascular endothelial cell vascular network formation in vitro under hyperoxic conditions. In vivo, Sema3C treatment of hyperoxic rats decreased lung neutrophil influx and preserved alveolar and lung vascular growth. Sema3C also preserved lung plexinA2 and Sema3C expression, alveolar epithelial cell proliferation and decreased lung apoptosis. In conclusion, the axonal guidance cue Sema3C promotes normal alveolar growth and may be worthwhile further investigating as a potential therapeutic target for lung repair.

  19. Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.

    OpenAIRE

    Felder Marcel; Sallin Pauline; Barbe Laurent; Haenni Beat; Gazdhar Amiq; Geiser Thomas; Guenat Olivier

    2012-01-01

    We present a microfluidic epithelial wound healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system a technique that is reported here ...

  20. Pulmonary alveolar microlithiliasis

    International Nuclear Information System (INIS)

    Fasihuddin, S.; Alawi, Malak H.; Abdulshakoor, Bothania M.

    2004-01-01

    We report a patient with plmonary alveolar microlithiliasis who was admitted to King Abdul-Aziz Hospital, Makkah, Kingdom of Saudi Arabia with chest pain, shortness of breath dry cough and swelling of lower limbs.The patient underwent chest radiolgraphs and computerized tomography scan showing multiple diffuse, almost symmetrical bilateral micronodulor opacities of calicific density. The diagnosis was confirmed after percuraneous lung biopsy from the patient. Cardiokinetics, diuretics and oxygen were administerd with slight improvement. (author)

  1. Proteinosis alveolar pulmonar

    Directory of Open Access Journals (Sweden)

    Concepción Sánchez Infante

    2011-12-01

    Full Text Available La proteinosis alveolar pulmonar es una enfermedad respiratoria crónica, caracterizada por alteración en el metabolismo del surfactante, lo que determina su acumulación anormal en el espacio alveolar. Es una enfermedad extremadamente rara. Se han reportado solamente 500 casos en la literatura. Se describió por primera vez en 1958. Se presenta un caso de proteinosis alveolar pulmonar en un lactante de 2 meses, con desnutrición proteico energética, que ingresa por dificultad respiratoria e hipoxemia, y, con imágenes radiológicas de tipo retículo-nodulillar, en vidrio deslustrado, en el cual se plantea inicialmente el diagnóstico de bronconeumonía. Ante la evolución desfavorable y no respuesta al tratamiento, se realizó un estudio para descartar enfermedades pulmonares crónicas. El paciente fallece y se confirma el diagnóstico por anatomía patológica. Se realiza una revisión del tema.

  2. Pulmonary alveolar microlithiasis

    International Nuclear Information System (INIS)

    Vallejo, Franco Javier; Vallejo, Alejandro; Parra, Maximiliano

    2007-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the diffuse and bilateral presence of calcium phosphate microlite in the alveolar spaces. The progression of this potentially lethal disease is show and most of the patients remain asymptomatic during years or decades, resulting in a show deterioration of the pulmonary function. The typical finding of the sand storm in the chest X-ray is characteristic of this entity. Mutations in the SLC34A2 gene that does the coding for the type II co-transporter of sodium phosphate were identified as responsible for this disease. Of the almost 600 cases, only 6 have been reported in Colombia. We are presenting a case of pulmonary alveolar microlite in a 27 year old man, with progressive respiratory distress whose diagnosis was made by the X-ray findings and confirmed by trans bronchial biopsy. In the 2 years follow-up, shows evolution towards deterioration of his respiratory function making him a candidate for lung transplantation.

  3. Alveolar Soft Part Sarcoma.

    Science.gov (United States)

    Jaber, Omar I; Kirby, Patricia A

    2015-11-01

    Alveolar soft part sarcoma is a rare neoplasm usually arising in the soft tissues of the lower limbs in adults and in the head and neck region in children. It presents primarily as a slowly growing mass or as metastatic disease. It is characterized by a specific chromosomal alteration, der(17)t(X:17)(p11:q25), resulting in fusion of the transcription factor E3 (TFE3) with alveolar soft part sarcoma critical region 1 (ASPSCR1) at 17q25. This translocation is diagnostically useful because the tumor nuclei are positive for TFE3 by immunohistochemistry. Real-time polymerase chain reaction to detect the ASPSCR1-TFE3 fusion transcript on paraffin-embedded tissue blocks has been shown to be more sensitive and specific than detection of TFE3 by immunohistochemical stain. Cathepsin K is a relatively recent immunohistochemical stain that can aid in the diagnosis. The recent discovery of the role of the ASPSCR1-TFE3 fusion protein in the MET proto-oncogene signaling pathway promoting angiogenesis and cell proliferation offers a promising targeted molecular therapy.

  4. Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.

    Science.gov (United States)

    Felder, Marcel; Sallin, Pauline; Barbe, Laurent; Haenni, Beat; Gazdhar, Amiq; Geiser, Thomas; Guenat, Olivier

    2012-02-07

    We present a microfluidic epithelial wound-healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow-focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system, a technique that is reported here for the first time. We demonstrate that alveolar epithelial cells cultured in a microfluidic environment preserve their phenotype before and after wounding. In addition, we report a wound-healing benefit induced by addition of HGF to the cell culture medium (19.2 vs. 13.5 μm h(-1) healing rate).

  5. The development and plasticity of alveolar type 1 cells

    Science.gov (United States)

    Yang, Jun; Hernandez, Belinda J.; Martinez Alanis, Denise; Narvaez del Pilar, Odemaris; Vila-Ellis, Lisandra; Akiyama, Haruhiko; Evans, Scott E.; Ostrin, Edwin J.; Chen, Jichao

    2016-01-01

    Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth. PMID:26586225

  6. p53 alterations in atypical alveolar hyperplasia of the human lung

    NARCIS (Netherlands)

    Slebos, R. J.; Baas, I. O.; Clement, M. J.; Offerhaus, G. J.; Askin, F. B.; Hruban, R. H.; Westra, W. H.

    1998-01-01

    Atypical alveolar hyperplasia (AAH) is a potential precursor lesion from which lung adenocarcinomas arise and may be a good target for studying the early events of lung tumorigenesis. We have previously shown that AAHs are neoplastic epithelial proliferations that often harbor activating mutations

  7. MRI of cerebral alveolar echinococcosis

    International Nuclear Information System (INIS)

    Tunaci, M.; Tunaci, A.; Engin, G.; Oezkorkmaz, B.; Ahishali, B.; Rozanes, I.

    1999-01-01

    Cerebral alveolar echinococcosis is rare. We report a case with multiple intracranial masses which show cauliflower-like contrast enhancement pattern on MRI. The lesions originated from hepatic involvement with invasion of the inferior vena cava. (orig.)

  8. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    International Nuclear Information System (INIS)

    Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

    2009-01-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFβ1-mediated lytic phase. EBV lytic reactivation by TGFβ1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM 1 81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  9. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Malizia, Andrea P.; Lacey, Noreen [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland); Walls, Dermot [School of Biotechnology, Dublin City University. Dublin, 9. Ireland (Ireland); Egan, Jim J. [Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae University Hospital. 44, Eccles Street. Dublin, 7. Ireland (Ireland); Doran, Peter P., E-mail: peter.doran@ucd.ie [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland)

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  10. Bulky PAH-DNA induced by exposure of a co-culture model of human alveolar macrophages and embryonic epithelial cells to atmospheric particulate pollution; Adduits encombrants a l'ADN dans des cocultures de cellules pulmonaires humaines exposees a une pollution atmospherique particulaire

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, Imane; Garcon, Guillaume; Billet, Sylvain; Shirali, Pirouz [Universite Lille Nord de France - Lille (France); Unite de Chimie Environnementale et Interactions sur le Vivant, MREI, Universite du Littoral Cote d' Opale, Dunkerque (France); Andre, Veronique; Le Goff, Jeremie; Sichel, Francois [GRECAN, Universite de Caen Basse-Normandie et centre Francois Baclesse, Caen (France); Roy Saint-Georges, Francoise; Mulliez, Philippe [Service de Pneumologie, Hopital Saint-Philibert, GHICL, Lille (France)

    2012-01-15

    Because of their deep penetration in human lungs, fine airborne particulate matter were described as mainly responsible for the deleterious effects of exposure to air pollution on health. Organic constituents are adsorbed on particles surface and, after inhalation, some (polycyclic aromatic hydrocarbons, PAHs) can be activated into reactive metabolites and can bind to DNA. The formation of bulky DNA adducts has been researched after exposure of mono-and co-cultures of alveolar macrophages (AM) and human embryonic human lung epithelial (L132), to fine air pollution particulate matter Air samples have been collected with cascade impactor and characterized: size distribution (92.15% < 2.5{mu}.m), specific surface area (1 m{sup 2}/g), inorganic (Fe, AI, Ca, Na, K, Mg, Pb, etc.) and organic compounds (PAHs, etc.). {sup 32}P post-labeling method was applied to detect bulky DNA adducts in AM and L132, in mono-and co-cultures, 72 h after their exposure to atmospheric particles at their Lethals and Effects concentrations or (LC or CE) to 50% (i.e. MA: EC{sub 50} = 74.63 {mu}g/mL and L132: LC-5-0 = 75.36 {mu}g/mL). Exposure to desorbed particles (MA: C1= 61.11 {mu}g/mL and L132 : C2 = 61.71 {mu}g/mL) and B[a]P (1 {mu}M) were included. Bulky PAH-DNA adducts were detected in AM in mono-culture after exposure to total particles (Pt), to B[a]P and desorbed particles (Pd). Whatever the exposure, no DNA adduct was detected in L132 in mono-culture. These results are coherent with the enzymatic activities of cytochrome P450 l Al in AM and L132. Exposure of co-culture to Pt, or Pd induced bulky adducts to DNA in AM but not in L132. Exposure to B[a]P alone has altered the DNA of AM and L132, in co-culture. Exposure to Pt is closer to the environmental conditions, but conferred an exposure to amounts of genotoxic agents compared to studies using organic extracts. The formation of bulky DNA adducts was nevertheless observed in AM exposed to Pt, in mono- or co-culture, indicating that

  11. Gas Exchange Disturbances Regulate Alveolar Fluid Clearance during Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    István Vadász

    2017-07-01

    Full Text Available Disruption of the alveolar–capillary barrier and accumulation of pulmonary edema, if not resolved, result in poor alveolar gas exchange leading to hypoxia and hypercapnia, which are hallmarks of acute lung injury and the acute respiratory distress syndrome (ARDS. Alveolar fluid clearance (AFC is a major function of the alveolar epithelium and is mediated by the concerted action of apically-located Na+ channels [epithelial Na+ channel (ENaC] and the basolateral Na,K-ATPase driving vectorial Na+ transport. Importantly, those patients with ARDS who cannot clear alveolar edema efficiently have worse outcomes. While hypoxia can be improved in most cases by O2 supplementation and mechanical ventilation, the use of lung protective ventilation settings can lead to further CO2 retention. Whether the increase in CO2 concentrations has deleterious or beneficial effects have been a topic of significant controversy. Of note, both low O2 and elevated CO2 levels are sensed by the alveolar epithelium and by distinct and specific molecular mechanisms impair the function of the Na,K-ATPase and ENaC thereby inhibiting AFC and leading to persistence of alveolar edema. This review discusses recent discoveries on the sensing and signaling events initiated by hypoxia and hypercapnia and the relevance of these results in identification of potential novel therapeutic targets in the treatment of ARDS.

  12. Developments in permeable and low permeability barriers

    International Nuclear Information System (INIS)

    Jefferis, S.A.; Norris, G.H.; Thomas, A.O.

    1997-01-01

    The concept of the reactive treatment zone whereby pollutants are attenuated as they move along a pathway in the ground has enabled a re-thinking of many of the concepts of containment. In particular it offers the potential for the control of the flux from a contaminated area by controlling the contaminant concentration in the pathway(s) as well as or instead of using a low permeability barrier. The paper outlines the basic concepts of the reactive treatment zone and the use of permeable and low permeability reactive systems. The paper then gives a case history of the installation of a permeable barrier using an in-situ reaction chamber

  13. Chronic Alcohol Ingestion Changes the Landscape of the Alveolar Epithelium

    Directory of Open Access Journals (Sweden)

    Charles A. Downs

    2013-01-01

    Full Text Available Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC. The cascading effect of tissue and phagocytic Nadph oxidase (Nox may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS for which hospitalized alcoholics are at an increased risk.

  14. True Fibroma of Alveolar Mucosa

    Directory of Open Access Journals (Sweden)

    Shankargouda Patil

    2014-01-01

    Full Text Available Benign fibrous overgrowths are often found in the oral cavity, almost always being reactive/irritational in nature. However, benign mesenchymal neoplasms of the fibroblasts are extremely uncommon. Here we report a case of “True Fibroma of Alveolar Mucosa” for its rarity.

  15. Intravascular bronchio-alveolar tumor

    International Nuclear Information System (INIS)

    Mata, J.M.; Caceres, J.; Prat, J.; Lopez, J.I.; Velilla, O.

    1991-01-01

    In 1975 Dail and Liebow described the clinical and pathological characteristics of a pulmonary tumor which they dominated intravascular bronchio-alveolar tumor (IVBAT). Our aim is to acquaint radiologists with the existence of this tumor by describing the radiologic findings in 2 patients with IVBAT, 1 with hepatic involvement ant the other with pulmonary osteoarthropathy. (author). 7 refs.; 2 figs

  16. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  17. Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system.

    Science.gov (United States)

    Rittirsch, Daniel; Flierl, Michael A; Nadeau, Brian A; Day, Danielle E; Huber-Lang, Markus S; Grailer, Jamison J; Zetoune, Firas S; Andjelkovic, Anuska V; Fasano, Alessio; Ward, Peter A

    2013-06-15

    Zonulin is a protein involved in the regulation of tight junctions (TJ) in epithelial or endothelial cells. Zonulin is known to affect TJ in gut epithelial cells, but little is known about its influences in other organs. Prehaptoglobin2 has been identified as zonulin and is related to serine proteases (MASPs, C1qrs) that activate the complement system. The current study focused on the role of zonulin in development of acute lung injury (ALI) in C57BL/6 male mice following intrapulmonary deposition of IgG immune complexes. A zonulin antagonist (AT-1001) and a related peptide with permeability agonist activities (AT-1002) were employed and given intratracheally or intravenously. Also, zonulin was blocked in lung with a neutralizing antibody. In a dose-dependent manner, AT-1001 or zonulin neutralizing antibody attenuated the intensity of ALI (as quantitated by albumin leak, neutrophil accumulation, and proinflammatory cytokines). A similar pattern was found using the bacterial lipopolysaccharide model of ALI. Using confocal microscopy on sections of injured lungs, staining patterns for TJ proteins were discontinuous, reduced, and fragmented. As expected, the leak of blood products into the alveolar space confirmed the passage of 3 and 20 kDa dextran, and albumin. In contrast to AT-1001, application of the zonulin agonist AT-1002 intensified ALI. Zonulin both in vitro and in vivo induced generation of complement C3a and C5a. Collectively, these data suggest that zonulin facilitates development of ALI both by enhancing albumin leak and complement activation as well as increased buildup of neutrophils and cytokines during development of ALI.

  18. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    and ceramide accumulation. We sought to investigate CF lung inflammation in the alveoli. METHODS: Lung tissue from 14 CF patients and four healthy individuals was analyzed for numbers of effector cells, elastin and collagen concentrations, inflammatory markers and density of Pseudomonas aeruginosa....... Additionally, desmosine and isodesmosine concentrations were determined in 52 urine specimens from CF patients to estimate the burden of elastase activities in respiratory secretions. RESULTS: Elastin concentration was significantly decreased and collagen significantly increased in CF alveolar tissues...... as compared to age-matched, healthy individuals. Elastin split products were significantly increased in urine samples from patients with CF and correlated inversely with age, indicating local tissue remodelling due to elastin degradation by unopposed proteolytic enzymes. Alveolar inflammation was also...

  19. Film Permeability Determination Using Static Permeability Cells

    Science.gov (United States)

    The permeability of tarps to soil fumigant pesticides varies depending on the active ingredient chemical: dimethyl disulfide (DMDS), methyl bromide, chloropicrin, or other. The diffusion rate can be represented by the mass transfer coefficient (MTC).

  20. Permeability prediction in chalks

    DEFF Research Database (Denmark)

    Alam, Mohammad Monzurul; Fabricius, Ida Lykke; Prasad, Manika

    2011-01-01

    The velocity of elastic waves is the primary datum available for acquiring information about subsurface characteristics such as lithology and porosity. Cheap and quick (spatial coverage, ease of measurement) information of permeability can be achieved, if sonic velocity is used for permeability p...... significantly using the effective specific surface as the fluid-flow concept. The FZI unit is appropriate for highly permeable sedimentary rocks such as sandstones and limestones that have small surface areas....

  1. The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells.

    Science.gov (United States)

    Yamada, Mitsuhiro; Kubo, Hiroshi; Ota, Chiharu; Takahashi, Toru; Tando, Yukiko; Suzuki, Takaya; Fujino, Naoya; Makiguchi, Tomonori; Takagi, Kiyoshi; Suzuki, Takashi; Ichinose, Masakazu

    2013-09-24

    The excess and persistent accumulation of fibroblasts due to aberrant tissue repair results in fibrotic diseases such as idiopathic pulmonary fibrosis. Recent reports have revealed significant changes in microRNAs during idiopathic pulmonary fibrosis and evidence in support of a role for microRNAs in myofibroblast differentiation and the epithelial-mesenchymal transition in the context of fibrosis. It has been reported that microRNA-21 is up-regulated in myofibroblasts during fibrosis and promotes transforming growth factor-beta signaling by inhibiting Smad7. However, expression changes in microRNA-21 and the role of microRNA-21 in epithelial-mesenchymal transition during lung fibrosis have not yet been defined. Lungs from saline- or bleomycin-treated C57BL/6 J mice and lung specimens from patients with idiopathic pulmonary fibrosis were analyzed. Enzymatic digestions were performed to isolate single lung cells. Lung epithelial cells were isolated by flow cytometric cell sorting. The expression of microRNA-21 was analyzed using both quantitative PCR and in situ hybridization. To induce epithelial-mesenchymal transition in culture, isolated mouse lung alveolar type II cells were cultured on fibronectin-coated chamber slides in the presence of transforming growth factor-β, thus generating conditions that enhance epithelial-mesenchymal transition. To investigate the role of microRNA-21 in epithelial-mesenchymal transition, we transfected cells with a microRNA-21 inhibitor. Total RNA was isolated from the freshly isolated and cultured cells. MicroRNA-21, as well as mRNAs of genes that are markers of alveolar epithelial or mesenchymal cell differentiation, were quantified using quantitative PCR. The lung epithelial cells isolated from the bleomycin-induced lung fibrosis model system had decreased expression of epithelial marker genes, whereas the expression of mesenchymal marker genes was increased. MicroRNA-21 was significantly upregulated in isolated lung epithelial

  2. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Chuan Junlan [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Li Yanzhen [Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (China); Yang Likai; Sun Xun [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Zhang Qiang [Peking University, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences (China); Gong Tao, E-mail: gongtaoy@126.com; Zhang Zhirong, E-mail: zrzzl@vip.sina.com [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China)

    2013-05-15

    The present study aimed at developing a drug delivery system targeting the densest site of tuberculosis infection, the alveolar macrophages (AMs). Rifampicin (RFP)-loaded solid lipid nanoparticles (RFP-SLNs) with an average size of 829.6 {+-} 16.1 nm were prepared by a modified lipid film hydration method. The cytotoxicity of RFP-SLNs to AMs and alveolar epithelial type II cells (AECs) was examined using MTT assays. The viability of AMs and AECs was above 80 % after treatment with RFP-SLNs, which showed low toxicity to both AMs and AECs. Confocal Laser Scanning Microscopy was employed to observe the interaction between RFP-SLNs and both AMs and AECs. After incubating the cells with RFP-SLNs for 2 h, the fluorescent intensity in AMs was more and remained longer (from 0.5 to 12 h) when compared with that in AECs (from 0.5 to 8 h). In vitro uptake characteristics of RFP-SLNs in AMs and AECs were also investigated by detection of intracellular RFP by High performance liquid chromatography. Results showed that RFP-SLNs delivered markedly higher RFP into AMs (691.7 ng/mg in cultured AMs, 662.6 ng/mg in primary AMs) than that into AECs (319.2 ng/mg in cultured AECs, 287.2 ng/mg in primary AECs). Subsequently, in vivo delivery efficiency and the selectivity of RFP-SLNs were further verified in Sprague-Dawley rats. Under pulmonary administration of RFP-SLNs, the amount of RFP in AMs was significantly higher than that in AECs at each time point. Our results demonstrated that solid lipid nanoparticles are a promising strategy for the delivery of rifampicin to alveolar macrophages selectively.

  3. Intracranial alveolar echinococcosis: CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Bensaid, A.H. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Dietemann, J.L. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Filippi de la Palavesa, M.M. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Klinkert, A. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Kastler, B. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Gangi, A. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Jacquet, G. (Dept. of Neurosurgery, Univ. Hospital, Besancon (France)); Cattin, F. (Dept. of Radiology, Univ. Hospital, Besancon (France))

    1994-05-01

    Intracranial alveolar echinococcosis is uncommon. We report a patient with right frontal lobe and palpebral lesions secondary to a primary hepatic focus with secondary lesion in the lung. The intracranial and palpebral cystic masses were totally removed and both proved to be alveolar hydatid cysts. An unusual feature in this case is CT and MRI demonstration of dural and bony extension. (orig.)

  4. Intracranial alveolar echinococcosis: CT and MRI

    International Nuclear Information System (INIS)

    Bensaid, A.H.; Dietemann, J.L.; Filippi de la Palavesa, M.M.; Klinkert, A.; Kastler, B.; Gangi, A.; Jacquet, G.; Cattin, F.

    1994-01-01

    Intracranial alveolar echinococcosis is uncommon. We report a patient with right frontal lobe and palpebral lesions secondary to a primary hepatic focus with secondary lesion in the lung. The intracranial and palpebral cystic masses were totally removed and both proved to be alveolar hydatid cysts. An unusual feature in this case is CT and MRI demonstration of dural and bony extension. (orig.)

  5. Pulmonary alveolar microlithiasis in children

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, H. [Center of Diagnostic Radiology, Frankfurt Univ. (Germany); Loercher, U. [Center of Diagnostic Radiology, Frankfurt Univ. (Germany); Kitz, R. [Center of Pediatrics, Frankfurt Univ. (Germany); Zielen, S. [Center of Pediatrics, Frankfurt Univ. (Germany); Ahrens, P. [Center of Pediatrics, Frankfurt Univ. (Germany); Koenig, R. [Inst. of Human Genetics, Frankfurt Univ. (Germany)

    1996-01-01

    Two asymptomatic Turkish sibs are presented, a 4-year-old boy and his 7-year-old sister, with pulmonary alveolar microlithiasis (PAM) confirmed by transbronchial lung biopsy and bronchoalveolar lavage. Chest radiographs and high resolution CT demonstrated wide-spread intra-alveolar calcifications in both lungs. The lesions were sharply defined and less than 1 mm in diameter. CT documented a high concentration of microliths along the bronchovascular bundles, the intralobular fissue and the (sub)pleural lung parenchyma. The combination of bronchoalveolar lavage and roentgenographic appearance in high resolution CT are characteristic and pathognomonic, and can confirm the diagnosis. The more severe changes in the elder sib and the radiographic controls suggest that the pulmonary disease may be progressive in our patients. The described family of consanguineous, unaffected parents with two affected and one healthy child confirmed the autosomal recessive inheritance of PAM (McKusick 265100). In addition, the affected girl had autosomal recessive Waardenburg-anophthalmia syndrome (McKusick 206920), raising the question of whether this is a chance occurrence or possibly a contiguous gene syndrome. (orig.)

  6. Inferior alveolar nerve block: Alternative technique.

    Science.gov (United States)

    Thangavelu, K; Kannan, R; Kumar, N Senthil

    2012-01-01

    Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages.

  7. Permeability of porour rhyolite

    Science.gov (United States)

    Cashman, K.; Rust, A.; Wright, H.; Roberge, J.

    2003-04-01

    The development of permeability in bubble-bearing magmas determines the efficiency of volatile escape during their ascent through volcanic conduits, which, in turn, controls their explosive potential. As permeability requires bubble connectivity, relationships between permeability and porosity in silicic magmas must be controlled by the formation, growth, deformation and coalescence of their constituent bubbles. Although permeability data on porous volcanic pyroclasts are limited, the database can be greatly extended by including data for ceramic and metallic foams1. Several studies indicate that a single number does not adequately describe the permeability of a foam because inertial effects, which predominate at high flow rates, cause deviations from Darcy's law. These studies suggest that permeability is best modeled using the Forschheimer equation to determine both the Darcy permeability (k1) and the non-Darcian (k2) permeability. Importantly, at the high porosities of ceramic foams (75-95%), both k1 and k2 are strongly dependent on pore size and geometry, suggesting that measurement of these parameters provides important information on foam structure. We determined both the connected porosity (by He-pycnometry) and the permeability (k1 and k2) of rhyolitic samples having a wide range in porosity (22-85%) and vesicle textures. In general, these data support previous observations of a power law relationship between connected porosity and Darcy permeability2. In detail, variations in k1 increase at higher porosities. Similarly, k2 generally increases in both mean and standard deviation with increasing porosity. Measurements made on three mutually perpendicular cores from individual pumice clasts suggest that some of the variability can be explained by anisotropy in the vesicle structure. By comparison with ceramic foams, we suggest that the remaining variability results from differences either in average vesicle size or, more likely, in the size of apertures

  8. Soils - Mean Permeability

    Data.gov (United States)

    Kansas Data Access and Support Center — This digital spatial data set provides information on the magnitude and spatial pattern of depth-weighted, mean soil permeability throughout the State of Kansas. The...

  9. Hydrogen permeability through metals

    International Nuclear Information System (INIS)

    Pisarev, A.A.; Tsvetkov, I.V.; Marenkov, E.D.; Yarko, S.S.

    2011-01-01

    The mechanisms of hydrogen permeability through one-layer and multi-layer membranes are considered. The effect of surface roughness, crystal defects, cracks and pores is described. Mathematical description of the processes is given [ru

  10. Permeable pavement study (Edison)

    Data.gov (United States)

    U.S. Environmental Protection Agency — While permeable pavement is increasingly being used to control stormwater runoff, field-based, side-by-side investigations on the effects different pavement types...

  11. Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury

    NARCIS (Netherlands)

    D. Hasan (Djo); P. Blankman (Paul); G.F. Nieman (Gary F.)

    2017-01-01

    textabstractSevere pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high

  12. Intestinal Permeability: The Basics

    Directory of Open Access Journals (Sweden)

    Ingvar Bjarnason

    1995-01-01

    Full Text Available The authors review some of the more fundamental principles underlying the noninvasive assessment of intestinal permeability in humans, the choice of test markers and their analyses, and the practical aspects of test dose composition and how these can be changed to allow the specific assessment of regional permeability changes and other intestinal functions. The implications of increased intestinal permeability in the pathogenesis of human disease is discussed in relation to findings in patients with Crohn’s disease. A common feature of increased intestinal permeability is the development of a low grade enteropathy, and while quantitatively similar changes may be found in Crohn’s disease these seem to predict relapse of disease. Moreover, factors associated with relapse of Crohn’s disease have in common an action to increase intestinal permeability. While increased intestinal permeability does not seem to be important in the etiology of Crohn’s disease it may be a central mechanism in the clinical relapse of disease.

  13. Drug-permeability and transporter assays in Caco-2 and MDCK cell lines.

    Science.gov (United States)

    Volpe, Donna A

    2011-12-01

    The human colon adenocarcinoma Caco-2 and Madin-Darby canine kidney epithelial cell lines provide in vitro tools to assess a drug's permeability and transporter interactions during discovery and development. The cells, when cultured on semiporous filters, form confluent monolayers that model the intestinal epithelial barrier for permeability, transporter and drug-interaction assays. The applications of these assays in pharmaceutical research include qualitative prediction and ranking of absorption, determining mechanism(s) of permeability, formulation effects on drug permeability, and the potential for transporter-mediated drug-drug interactions. This review focuses on recent examples of Caco-2 and Madin-Darby canine kidney cells assays for drug permeability including transfected and knock-down cells, miniaturization and automation, and assay combinations to better understand and predict intestinal drug absorption.

  14. Multibreath alveolar oxygen tension imaging.

    Science.gov (United States)

    Clapp, Justin; Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Shaghaghi, Hoora; Siddiqui, Sarmad; Rossman, Milton D; Rizi, Rahim R

    2016-10-01

    This study tested the ability of a multibreath hyperpolarized HP (3) He MRI protocol to increase the accuracy of regional alveolar oxygen tension (PA O2 ) measurements by lessening the influence of gas-flow artifacts. Conventional single-breath PA O2 measurement has been susceptible to error induced by intervoxel gas flow, particularly when used to study subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD). Both single-breath and multibreath PA O2 imaging schemes were implemented in seven human subjects (one healthy, three asymptomatic smokers, and three COPD). The number and location of voxels with nonphysiologic PA O2 values generated by intervoxel gas flow were compared between the two protocols. The multibreath scheme resulted in a significantly lower total percentage of nonphysiologic PA O2 values (6.0%) than the single-breath scheme (13.7%) (P = 0.006). PA O2 maps showed several patterns of gas-flow artifacts that were present in the single-breath protocol but mitigated by the multibreath approach. Multibreath imaging also allowed for the analysis of slow-filling areas that presented no signal after a single breath. A multibreath approach enhances the accuracy and completeness of noninvasive PA O2 measurement by significantly lessening the proportion of nonphysiologic values generated by intervoxel gas flow. Magn Reson Med 76:1092-1101, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  15. The influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction in rats.

    Science.gov (United States)

    Dias-da-Silva, Marco A; Pereira, Andresa C; Marin, Miguel Cc; Salgado, Miguel Ac

    2013-10-01

    The Copaiba oil has been used as an auxiliary treatment of inflammations, skin disorders and stomach ulcers, however, in dentistry, this "alternative" medicine has not been investigated yet. The purpose of this study was to evaluate the influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction. Twenty-eight wistar male rats had their lower first molar teeth extracted. Subsequently, they were divided in four groups, according to the treatment performed: (a) alveolar socket irrigation with copaiba oil; (b) alveolar socket irrigation with physiological serum; (c) daily gavage with copaiba oil or (d) daily gavage with physiological serum. After the sacrifice, the mandibles were removed and processed in order to obtain decalcified histological sections. The results demonstrated high level of epithelial migration, small number of inflammatory cells and vascular enhancement in the animals which received systemic administration of copaiba oil. The rats treated with topic administration of copaiba oil presented ulcerations and large number of inflammatory cells. An increased bone neoformation was observed in both groups treated with copaiba oil when compared with placebo group. It could be concluded that topic or systemic administration of copaiba oil leads to a better alveolar bone healing, however the topic application on connective tissue should be carefully considered, regarding the whole socket wound healing. Key words:Alveolar wound healing, oil-resin, copaiba.

  16. [Cleft lip, alveolar and palate sequelae. Proposal of new alveolar score by the Alveolar Cleft Score (ACS) classification].

    Science.gov (United States)

    Molé, C; Simon, E

    2015-06-01

    The management of cleft lip, alveolar and palate sequelae remains problematic today. To optimize it, we tried to establish a new clinical index for diagnostic and prognostic purposes. Seven tissue indicators, that we consider to be important in the management of alveolar sequelae, are listed by assigning them individual scores. The final score, obtained by adding together the individual scores, can take a low, high or maximum value. We propose a new classification (ACS: Alveolar Cleft Score) that guides the therapeutic team to a prognosis approach, in terms of the recommended surgical and prosthetic reconstruction, the type of medical care required, and the preventive and supportive therapy to establish. Current studies are often only based on a standard radiological evaluation of the alveolar bone height at the cleft site. However, the gingival, the osseous and the cellular areas bordering the alveolar cleft sequelae induce many clinical parameters, which should be reflected in the morphological diagnosis, to better direct the surgical indications and the future prosthetic requirements, and to best maintain successful long term aesthetic and functional results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model

    Science.gov (United States)

    Weber, Nina C.; van der Sluijs, Koen; Hackl, Florian; Hotz, Lorenz; Dahan, Albert; Hollmann, Markus W.; Berger, Marc M.

    2014-01-01

    We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (IV) bolus injection had no effect. The aim of the present study was to characterize whether continuous IV infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of IV S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered IV over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by IV lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by IV S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by IV S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of IV S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport. PMID:25386677

  18. Biostable glucose permeable polymer

    DEFF Research Database (Denmark)

    2017-01-01

    A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing...... a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer...

  19. Interfacial stress affects rat alveolar type II cell signaling and gene expression

    OpenAIRE

    Hobi, Nina; Ravasio, Andrea; Haller, Thomas

    2012-01-01

    Previous work from our group (Ravasio A, Hobi N, Bertocchi C, Jesacher A, Dietl P, Haller T. Am J Physiol Cell Physiol 300: C1456–C1465, 2011.) showed that contact of alveolar epithelial type II cells with an air-liquid interface (IAL) leads to a paradoxical situation. It is a potential threat that can cause cell injury, but also a Ca2+-dependent stimulus for surfactant secretion. Both events can be explained by the impact of interfacial tensile forces on cellular structures. Here, the streng...

  20. Orthopantomographic study of the alveolar bone level on periodontal disease

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ki Sik; You, Dong Soo [College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1972-11-15

    The author had measured the alveolar bone level of periodontal disease on 50 cases of orthopantomogram to detect the degree of alveolar bone resorption of both sexes of Korean. The results were obtained as follows; 1. Alveolar bone resorption of mesial and distal portion was similar in same patient. 2. The order of alveolar bone resorption was mandibular anterior region, posterior region, canine and premolar region of both jaws. 3. The degree of alveolar bone destruction was severe in shorter root length than longer one. 4. The degree of alveolar bone resorption was severe in fourth decades.

  1. Orthopantomographic study of the alveolar bone level on periodontal disease

    International Nuclear Information System (INIS)

    Lee, Ki Sik; You, Dong Soo

    1972-01-01

    The author had measured the alveolar bone level of periodontal disease on 50 cases of orthopantomogram to detect the degree of alveolar bone resorption of both sexes of Korean. The results were obtained as follows; 1. Alveolar bone resorption of mesial and distal portion was similar in same patient. 2. The order of alveolar bone resorption was mandibular anterior region, posterior region, canine and premolar region of both jaws. 3. The degree of alveolar bone destruction was severe in shorter root length than longer one. 4. The degree of alveolar bone resorption was severe in fourth decades.

  2. Perawatan Ortodontik Gigi Anterior Berjejal dengan Tulang Alveolar yang Tipis

    Directory of Open Access Journals (Sweden)

    Miesje K. Purwanegara

    2015-09-01

    Full Text Available Anterior teeth movement in orthodontic treatment is limited to labiolingual direction by very thin alveolar bone. An uncontrolled anterior tooth movement to labiolingual direction can cause alveolar bone perforation at its root segment. This case report is to remind us that alveolar bone thickness limits orthodontc tooth movement. A case of crowded anterior teeth with thin alveolar bone in malocclusion I is reported. This case is treated using adgewise orthodontic appliance. Protraction of anterior teeth is anticipated due to thin alveolar bone on the anterior surface. The conclusion is although the alveolar bone surrounding the crowded anterior teeth is thin, by controlling the movement the teeth reposition is allowed.

  3. When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine.

    Science.gov (United States)

    Beers, Michael F; Moodley, Yuben

    2017-07-01

    Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of "lung epithelial cell biology pioneers," which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.

  4. Fibrosis of Two: Epithelial Cell-Fibroblast Interactions in Pulmonary Fibrosis

    Science.gov (United States)

    Sakai, Norihiko; Tager, Andrew M.

    2013-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the “pas de deux” (steps of two), or perhaps more appropriate to IPF pathogenesis, the “folie à deux” (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their “fibrosis of two”, including transforming growth factor-β, connective tissue growth factor, sonic hedgehog, prostaglandin E2, angiotensin II and reactive oxygen species. PMID:23499992

  5. Role of epithelial cells in idiopathic pulmonary fibrosis: from innocent targets to serial killers.

    Science.gov (United States)

    Selman, Moisés; Pardo, Annie

    2006-06-01

    Idiopathic pulmonary fibrosis (IPF), a progressive and relentless lung scarring of unknown etiology, has been recognized as the most lethal interstitial lung disease. Despite the growing interest in IPF, the precise molecular mechanisms underlying the development of fibrosis and leading to the irreversible destruction of the lung are still unknown. Recently, it has been proposed that IPF, instead of being a chronic inflammatory disorder, results from multiple cycles of epithelial cell injury and activation. In turn, active alveolar epithelial cells provoke the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci and the exaggerated accumulation of extracellular matrix, mirroring abnormal wound repair. In this article, some characteristics of the alveolar epithelium are briefly outlined, and the fibrogenic mechanisms specifically operated by active abnormal epithelial cells are examined.

  6. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    International Nuclear Information System (INIS)

    Shin, Jung Ar; Chung, Jin Sil; Cho, Sang-Ho; Kim, Hyung Jung; Yoo, Young Do

    2013-01-01

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H 2 O 2 ) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H 2 O 2 treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells

  7. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Ar [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Chung, Jin Sil [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Cho, Sang-Ho [Department of Pathology, Pochon CHA University, College of Medicine, Gyeonggi-do (Korea, Republic of); Kim, Hyung Jung, E-mail: khj57@yuhs.ac.kr [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Yoo, Young Do, E-mail: ydy1130@korea.ac.kr [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

    2013-09-20

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

  8. Bone graft healing in alveolar osteoplasty in patients with unilateral lip, alveolar process, and palate clefts.

    Science.gov (United States)

    Rychlik, Dariusz; Wójcicki, Piotr

    2012-01-01

    Secondary osteoplasty by means of autogenic spongy bone grafting is the most common procedure used in the reconstruction of the continuity of the maxillary alveolar process. The aim of the study was to analyze retrospectively the effect of certain factors on the course of the bone graft healing process in patients with unilateral complete clefts of the lip, alveolar process, and palate. The investigations involved 62 children aged 8 to 14 years (mean age, 11 years) with unilateral complete cleft of the lip, alveolar process, and palate operated on at the Clinic of Plastic Surgery in Polanica Zdrój from November 2007 to April 2009. All the procedures consisted in the reconstruction of the maxillary alveolar process by means of autogenic spongy bone grafting from the iliac bone. The analysis was performed on the basis of computed tomography scans presenting maxillary alveolar processes in the horizontal cross-sectional planes performed on the second or third postoperative day and after 6 months. They were used as the basis for the measurement of the volume and density (condensation) of the bone graft, the surface of its adhesion to the maxillary alveolar bone, and the volume and density of the healed bone. The following correlation coefficients were determined: between the adhesion surface of the bone to the alveolar bone and the volume of the healed bone, between the adhesion surface of the bone to the alveolar bone and the density of the healed bone, and between the density of the graft and the volume of the healed bone. Increasing the surface of the graft adhesion to the bone ridges of the alveolar cleft contributes to increased volume of the healed bone and slows down the increase in its density (on 6-month follow-up). Crushing of the bone graft increases its resorption and reduces volume of the healed bone.

  9. Diagnosis of hydrostatic versus increased permeability pulmonary edema with chest radiographic criteria in critically ILL patients

    International Nuclear Information System (INIS)

    Aberle, D.R.; Wiener-Kronish, J.P.; Webb, W.R.; Matthay, M.A.

    1987-01-01

    To evaluate chest radiographic criteria in distinguishing mechanisms of pulmonary edema, the authors studied 45 intubated patients with extensive edema. Edema type was clinically classified by the ratio of alveolar edema-to-plasma protein concentration in association with compatible clinical/hemodynamic parameters. Chest films were scored as hydrostatic, permeability, or mixed by three readers in blinded fashion based on cardiac size, vascular pedicle width, distribution of edema, effusions, peribronchial cuffs, septal lines, or air bronchograms. Overall radiographic score accurately identified 87% of patients with hydrostatic edema but only 60% of those with permeability edema. Edema distribution was most discriminating, with a patchy peripheral pattern relatively specific for clinical permeability edema. Hydrostatic features on chest radiograph were common with permeability edema, including effusions (36%), widened pedicle (56%), cuffs (72%), or septa (40%). The authors conclude that the chest radiograph is limited in distinguishing edema mechanism in the face of extensive pulmonary edema

  10. Ethamsylate and lung permeability in ventilated immature newborn rabbits.

    Science.gov (United States)

    Amato, M; Sun, B; Robertson, B

    1994-01-01

    The leakage of proteins in the immature neonatal lung can reduce the effect of exogenous surfactant. The effect of ethamsylate, a more specific prostaglandin inhibitor than indomethacin and aspirin-like drugs, on alveolar albumin leak was studied in a group of 27 immature newborn rabbits (gestational age 27 days). A pilot study was carried out using 4 animals and low-dose ethamsylate (10 mg/kg). A second group of animals (n = 12) received at birth, by intravenous injection, ethamsylate (50 mg/kg) and 10% human albumin (7 ml/kg). Animals not receiving ethamsylate (n = 11) served as control group. After 30 min of artificial ventilation with standard tidal volume (10 ml/kg) the lungs were lavaged and the amount of human albumin in lung lavage fluid was determined by immunodiffusion. No statistically significant differences were found in lung-thorax compliance and vascular to alveolar albumin leak between ethamsylate-treated animals and controls (p > 0.5). However, there was a statistically significant negative correlation between protein leak and lung compliance (r = -0.41; p ethamsylate administration on neonatal lung permeability in the immature neonate confirming that lung permeability is inversely related to compliance.

  11. Alveolar Ridge Carcinoma. Two Cases Report

    International Nuclear Information System (INIS)

    Pupo Triguero, Raul J; Vivar Bauza, Miriam; Alvarez Infante, Elisa

    2008-01-01

    Two cases with alveolar ridge carcinoma due to prosthetist traumatism are discussed in this paper, after 9 and 10 years of using dental prosthesis. Both patients began with disturbance in the alveolar ridge. The clinical examination and biopsy showed a well differenced carcinoma. The treatment was radical surgery and radiotherapy in the first patient, and conservative surgery with radiotherapy in the second case .The patients had xerostomia after radiotherapy and the woman had difficulties with mastication. The advantages and disadvantages of the treatment were discussed, focused on the prevention and treatment for oral

  12. Replication of cultured lung epithelial cells

    International Nuclear Information System (INIS)

    Guzowski, D.; Bienkowski, R.

    1986-01-01

    The authors have investigated the conditions necessary to support replication of lung type 2 epithelial cells in culture. Cells were isolated from mature fetal rabbit lungs (29d gestation) and cultured on feeder layers of mitotically inactivated 3T3 fibroblasts. The epithelial nature of the cells was demonstrated by indirect immunofluorescent staining for keratin and by polyacid dichrome stain. Ultrastructural examination during the first week showed that the cells contained myofilaments, microvilli and lamellar bodies (markers for type 2 cells). The following changes were observed after the first week: increase in cell size; loss of lamellar bodies and appearance of multivesicular bodies; increase in rough endoplasmic reticulum and golgi; increase in tonafilaments and well-defined junctions. General cell morphology was good for up to 10 wk. Cells cultured on plastic surface degenerated after 1 wk. Cell replication was assayed by autoradiography of cultures exposed to ( 3 H)-thymidine and by direct cell counts. The cells did not replicate during the first week; however, between 2-10 wk the cells incorporated the label and went through approximately 6 population doublings. They have demonstrated that lung alveolar epithelial cells can replicate in culture if they are maintained on an appropriate substrate. The coincidence of ability to replicate and loss of markers for differentiation may reflect the dichotomy between growth and differentiation commonly observed in developing systems

  13. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

  14. Interfacial stress affects rat alveolar type II cell signaling and gene expression.

    Science.gov (United States)

    Hobi, Nina; Ravasio, Andrea; Haller, Thomas

    2012-07-01

    Previous work from our group (Ravasio A, Hobi N, Bertocchi C, Jesacher A, Dietl P, Haller T. Am J Physiol Cell Physiol 300: C1456-C1465, 2011.) showed that contact of alveolar epithelial type II cells with an air-liquid interface (I(AL)) leads to a paradoxical situation. It is a potential threat that can cause cell injury, but also a Ca(2+)-dependent stimulus for surfactant secretion. Both events can be explained by the impact of interfacial tensile forces on cellular structures. Here, the strength of this mechanical stimulus became also apparent in microarray studies by a rapid and significant change on the transcriptional level. Cells challenged with an I(AL) in two different ways showed activation/inactivation of cellular pathways involved in stress response and defense, and a detailed Pubmatrix search identified genes associated with several lung diseases and injuries. Altogether, they suggest a close relationship of interfacial stress sensation with current models in alveolar micromechanics. Further similarities between I(AL) and cell stretch were found with respect to the underlying signaling events. The source of Ca(2+) was extracellular, and the transmembrane Ca(2+) entry pathway suggests the involvement of a mechanosensitive channel. We conclude that alveolar type II cells, due to their location and morphology, are specific sensors of the I(AL), but largely protected from interfacial stress by surfactant release.

  15. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y.; Fong, Guo-Hua; Sakmar, Thomas P.; Rafii, Shahin; Ding, Bi-Sen

    2016-01-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

  16. Expression and Role of Oct3/4 in Injury-Repair Process of Rat Alveolar Epithelium after 5-Fu Treatment

    Directory of Open Access Journals (Sweden)

    Wen-ya Li

    2017-01-01

    Full Text Available Objective. We aimed to investigate how the embryonic stem cell-related gene Oct3/4 changes during the injury-repair process of distal pulmonary epithelium induced by 5-fluorouracil (5-Fu. Methods. We have developed the lung injury model induced by 5-Fu and observed the dynamic changes of Oct3/4 by indirect immunofluorescence, Western blot, and quantitative real-time PCR. Immunofluorescence double staining was used to compare the positions of Oct3/4(+ cells and other reported alveolar epithelial stem cells. Results. Oct3/4(+ cells were not found in normal rat lung epithelial cells. However, after treatment with 5-Fu, Oct3/4(+ cells appeared at 12 h, reached the peak at 24 h, then decreased at 48 h, and eventually disappeared at 72 h. Oct3/4 was localized in the nucleus. We found that the sites of Clara cell secretory protein and surfactant protein-C dual positive cells were apparently different from Oct3/4(+ cells. Conclusions. Our results revealed that, in rat alveolar epithelium, expression of Oct3/4 could be induced after treatment with 5-Fu, then decreased gradually, and was silenced following the alveolar epithelial differentiation. We hold that Oct3/4(+ cells are lung stem cells, which can provide new evidence for identification and isolation of lung epithelial stem cells.

  17. Iatrogenic injury to the inferior alveolar nerve

    DEFF Research Database (Denmark)

    Hillerup, Søren

    2008-01-01

    The purpose of this prospective, non-randomised, descriptive study is to characterise the neurosensory deficit and associated neurogenic discomfort in 52 patients with iatrogenic injury to the inferior alveolar nerve (IAN). All patients were examined and followed up according to a protocol...

  18. Alveolar Thin Layer Flows and Surfactant Dynamics

    Science.gov (United States)

    Roumie, Ahmad; Jbaily, Abdulrahman; Szeri, Andrew J.

    2017-11-01

    Pulmonary surfactants play a vital role in everyday respiration. They regulate surface tension in the lungs by diffusing through the hypophase, a liquid layer that lines the interior surface of the alveoli, and adsorbing to the existing air-fluid interface. This decreases the equilibrium surface tension value by as much as a factor of 3, minimizing breathing effort and preventing lung collapse at the end of exhalation. Given that the hypophase thickness h lies within the range 0.1 μm < h <0.5 μm , and that the average alveolar radius R is 100 μm , for some purposes the hypophase may usefully be modeled as a fluid layer on a flat sheet representing the alveolar wall. Moreover, because of the large aspect ratio, the lubrication approximation can be applied. The aim of the present work is to study the interaction between the straining of the alveolar wall and the fluid flow in the hypophase. The analysis is governed by the relative magnitudes of the time scales of surfactant diffusion, adsorption, desorption, viscous dissipation and sheet straining. Cases of particular interest include non-uniform surfactant concentration at the interface, leading to Marangoni flows and a non-uniform hypophase thickness profile. The analytical formulation and numerical simulations are presented. This work is motivated by a need to understand alveolar deformation during breathing, and to do so in a way that derives from improved understanding of the fluid mechanics of the problem.

  19. Alveolar ridge augmentation by osteoinduction in rats

    DEFF Research Database (Denmark)

    Pinholt, E M; Bang, G; Haanaes, H R

    1990-01-01

    The purpose of this study was to evaluate bone substitutes for alveolar ridge augmentation by osteoinduction. Allogenic, demineralized, and lyophilized dentin and bone was tested for osteoinductive properties in order to establish an experimental model for further studies. Implantations were perf...

  20. Alveolar proteinosis associated with aluminium dust inhalation.

    Science.gov (United States)

    Chew, R; Nigam, S; Sivakumaran, P

    2016-08-01

    Secondary alveolar proteinosis is a rare lung disease which may be triggered by a variety of inhaled particles. The diagnosis is made by detection of anti-granulocyte-macrophage colony-stimulating factor antibodies in bronchoalveolar lavage fluid, which appears milky white and contains lamellar bodies. Aluminium has been suggested as a possible cause, but there is little evidence in the literature to support this assertion. We report the case of a 46-year-old former boilermaker and boat builder who developed secondary alveolar proteinosis following sustained heavy aluminium exposure. The presence of aluminium was confirmed both by histological examination and metallurgical analysis of a mediastinal lymph node. Despite cessation of exposure to aluminium and treatment with whole-lung lavage which normally results in improvements in both symptoms and lung function, the outcome was poor and novel therapies are now being used for this patient. It may be that the natural history in aluminium-related alveolar proteinosis is different, with the metal playing a mediating role in the disease process. Our case further supports the link between aluminium and secondary alveolar proteinosis and highlights the need for measures to prevent excessive aluminium inhalation in relevant industries. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Exogenous hydrogen sulfide (H2S protects alveolar growth in experimental O2-induced neonatal lung injury.

    Directory of Open Access Journals (Sweden)

    Arul Vadivel

    Full Text Available 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.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.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.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.

  2. Acute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in Rhesus monkeys exposed to ozone

    International Nuclear Information System (INIS)

    Castleman, W.L.; Dungworth, D.L.; Schwartz, L.W.; Tyler, W.S.

    1980-01-01

    The pathogenesis of acute respiratory bronchiolitis was examined in Rhesus monkeys exposed to 0.8 ppM ozone for 4 to 50 hours. Epithelial injury and renewal were qualitatively and quantitatively characterized by correlated techniques of scanning and transmission electron microscopy as well as by light-microscopic autoradiography following labeling with tritiated thymidine. Extensive degeneration and necrosis of Type 1 epithelial cells occurred on the respiratory bronchiolar wall during the initial 4 to 12 hours of exposure. Increased numbers of labeled epithelial cells were present in this region after 18 hours of exposure, and the highest labeling index (18%) was measured after 50 hours of exposure. Most (67 to 80%) of the labeled cells and all the mitotic epithelial cells (22) observed ultrastructurally were cuboidal bronchiolar epithelial cells. Of the labeled epithelial cells, 20 to 33% were Type 2 epithelial cells. After 50 hours of exposure the respiratory bronchiolar epithelium was hyperplastic. The predominant inflammatory cell in respiratory bronchiolar exudate was the alveolar macrophage. Monkeys that were exposed for 50 hours and allowed to recover in unozonized air for 7 days had incomplete resolution of respiratory bronchiolar epithelial hyperplasia. The results indicate that Type 1 epithelial cells lining respiratory bronchioles are the cell types most sensitive to injury and that both cuboidal bronchiolar epithelial cells and Type 2 epithelial cells function as stem cells in epithelial renewal

  3. Permeability of the small intestine after intra-arterial injection of histamine-type mediators and irradiation

    International Nuclear Information System (INIS)

    Kingham, J.G.C.; Loehry, C.A.

    1976-01-01

    Permeability and selectivity of rabbit small intestine were estimated by a perfusion technique after intra-arterial injection of histamine-type mediators and an intestinal dose of 1.5 Mr gamma irradiation. It was shown that the histamine-type mediators caused an increase in capillary permeability which produced an overall moderate increase in transmucosal permeability with a moderate loss of selectivity. Local intestinal irradiation caused a very marked increase in permeability and a profound loss of selectivity. It was felt that this was produced partly by an increase in capillary permeability but largely by damage to the epithelial basement membrane. It is concluded that the intestinal capillary endothelium is both rate-limiting and selective, though not to a major degree in either case. The epithelial basement membrane, however, appears to be both rate-limiting and markedly selective. (author)

  4. Permeability measuremens of brazilian Eucalyptus

    Directory of Open Access Journals (Sweden)

    Marcio Rogério da Silva

    2010-09-01

    Full Text Available The permeability of Brazilian Eucalyptus grandis and Eucalyptus citriodora wood was measured in a custom build gas analysis chamber in order to determine which species could be successfully treated with preservatives. Liquid permeability was tested using an emulsion of Neen oil and a control of distillated water. Air was used to test the gas phase permeability. For both Eucalyptus grandis and Eucalyptus citriodora, the longitudinal permeability of gas was shown to be about twice as great as the liquid phase permeability. No radial permeability was observed for either wood. The permeability of air and water through the sapwood of Eucalyptus grandis was greater than that through the sapwood of Eucalyptus citriodora. The permeability of neen oil preservative through the sapwood of Eucalyptus grandis was also greater than through the sapwood of E. Citradora, but the difference was not statistically significant. Scanning Electron Microscopy images showed that the distribution and obstruction in the vessels could be correlated with observed permeability properties. Irrespective of the causes of differences in permeability between the species, the fluid phase flux through the sapwood of both species was significant, indicating that both Eucalyptus grandis and Eucalyptus citriodora could be successfully treated with wood preservative.

  5. Cytokine Tuning of Intestinal Epithelial Function

    Directory of Open Access Journals (Sweden)

    Caroline Andrews

    2018-06-01

    Full Text Available The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

  6. Alternatives to Autologous Bone Graft in Alveolar Cleft Reconstruction: The State of Alveolar Tissue Engineering.

    Science.gov (United States)

    Liang, Fan; Leland, Hyuma; Jedrzejewski, Breanna; Auslander, Allyn; Maniskas, Seija; Swanson, Jordan; Urata, Mark; Hammoudeh, Jeffrey; Magee, William

    2018-05-01

    Alveolar cleft reconstruction has historically relied on autologous iliac crest bone grafting (ICBG), but donor site morbidity, pain, and prolonged hospitalization have prompted the search for bone graft substitutes. The authors evaluated bone graft substitutes with the highest levels of evidence, and highlight the products that show promise in alveolar cleft repair and in maxillary augmentation. This comprehensive review guides the craniofacial surgeon toward safe and informed utilization of biomaterials in the alveolar cleft.A literature search was performed to identify in vitro human studies that fulfilled the following criteria: Level I or Level II of evidence, ≥30 subjects, and a direct comparison between a autologous bone graft and a bone graft substitute. A second literature search was performed that captured all studies, regardless of level of evidence, which evaluated bone graft substitutes for alveolar cleft repair or alveolar augmentation for dental implants. Adverse events for each of these products were tabulated as well.Sixteen studies featuring 6 bone graft substitutes: hydroxyapatite, demineralized bone matrix (DBM), β-tricalcium phosphate (TCP), calcium phosphate, recombinant human bone morphogenic protein-2 (rhBMP-2), and rhBMP7 fit the inclusion criteria for the first search. Through our second search, the authors found that DBM, TCP, rhBMP-2, and rhBMP7 have been studied most extensively in the alveolar cleft literature, though frequently in studies using less rigorous methodology (Level III evidence or below). rhBMP-2 was the best studied and showed comparable efficacy to ICBG in terms of volume of bone regeneration, bone density, and capacity to accommodate tooth eruption within the graft site. Pricing for products ranged from $290 to $3110 per 5 mL.The balance between innovation and safety is a complex process requiring constant vigilance and evaluation. Here, the authors profile several bone graft substitutes that demonstrate the most

  7. Endoscopic sensing of alveolar pH.

    Science.gov (United States)

    Choudhury, D; Tanner, M G; McAughtrie, S; Yu, F; Mills, B; Choudhary, T R; Seth, S; Craven, T H; Stone, J M; Mati, I K; Campbell, C J; Bradley, M; Williams, C K I; Dhaliwal, K; Birks, T A; Thomson, R R

    2017-01-01

    Previously unobtainable measurements of alveolar pH were obtained using an endoscope-deployable optrode. The pH sensing was achieved using functionalized gold nanoshell sensors and surface enhanced Raman spectroscopy (SERS). The optrode consisted of an asymmetric dual-core optical fiber designed for spatially separating the optical pump delivery and signal collection, in order to circumvent the unwanted Raman signal generated within the fiber. Using this approach, we demonstrate a ~100-fold increase in SERS signal-to-fiber background ratio, and demonstrate multiple site pH sensing with a measurement accuracy of ± 0.07 pH units in the respiratory acini of an ex vivo ovine lung model. We also demonstrate that alveolar pH changes in response to ventilation.

  8. Silver Nanoparticles in Alveolar Bone Surgery Devices

    Directory of Open Access Journals (Sweden)

    Stefano Sivolella

    2012-01-01

    Full Text Available Silver (Ag ions have well-known antimicrobial properties and have been applied as nanostrategies in many medical and surgical fields, including dentistry. The use of silver nanoparticles (Ag NPs may be an option for reducing bacterial adhesion to dental implant surfaces and preventing biofilm formation, containing the risk of peri-implant infections. Modifying the structure or surface of bone grafts and membranes with Ag NPs may also prevent the risk of contamination and infection that are common when alveolar bone augmentation techniques are used. On the other hand, Ag NPs have revealed some toxic effects on cells in vitro and in vivo in animal studies. In this setting, the aim of the present paper is to summarize the principle behind Ag NP-based devices and their clinical applications in alveolar bone and dental implant surgery.

  9. Temporary Blindness after Inferior Alveolar Nerve Block.

    Science.gov (United States)

    Barodiya, Animesh; Thukral, Rishi; Agrawal, Shaila Mahendra; Rai, Anshul; Singh, Siddharth

    2017-03-01

    Inferior Alveolar Nerve Block (IANB) anaesthesia is one of the common procedures in dental clinic. This procedure is safe, but complications may still occur. Ocular complications such as diplopia, loss of vision, or ophthalmoplegia are extremely rare. This case report explains an event where due to individual anatomic variation of the sympathetic vasoconstrictor nerve and maxillary and middle meningeal arteries, intravascular administration of anaesthetic agent caused unusual ocular signs and symptoms such as temporary blindness.

  10. Inferior alveolar nerve block: Alternative technique

    OpenAIRE

    Thangavelu, K.; Kannan, R.; Kumar, N. Senthil

    2012-01-01

    Background: Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple techni...

  11. Alveolar ridge keratosis - a retrospective clinicopathological study

    Science.gov (United States)

    2013-01-01

    Background Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK. Material and methods The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient’s gender, age, anatomical location, tobacco and alcohol use were analyzed. Results Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia. Conclusion Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK. PMID:23587097

  12. Protein kinase D is increased and activated in lung epithelial cells and macrophages in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Gan, Huachen; McKenzie, Raymond; Hao, Qin; Idell, Steven; Tang, Hua

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and usually fatal lung disease of unknown etiology for which no effective treatments currently exist. Hence, there is a profound need for the identification of novel drugable targets to develop more specific and efficacious therapeutic intervention in IPF. In this study, we performed immunohistochemical analyses to assess the cell type-specific expression and activation of protein kinase D (PKD) family kinases in normal and IPF lung tissue sections. We also analyzed PKD activation and function in human lung epithelial cells. We found that PKD family kinases (PKD1, PKD2 and PKD3) were increased and activated in the hyperplastic and regenerative alveolar epithelial cells lining remodeled fibrotic alveolar septa and/or fibroblast foci in IPF lungs compared with normal controls. We also found that PKD family kinases were increased and activated in alveolar macrophages, bronchiolar epithelium, and honeycomb cysts in IPF lungs. Interestingly, PKD1 was highly expressed and activated in the cilia of IPF bronchiolar epithelial cells, while PKD2 and PKD3 were expressed in the cell cytoplasm and nuclei. In contrast, PKD family kinases were not apparently increased and activated in IPF fibroblasts or myofibroblasts. We lastly found that PKD was predominantly activated by poly-L-arginine, lysophosphatidic acid and thrombin in human lung epithelial cells and that PKD promoted epithelial barrier dysfunction. These findings suggest that PKD may participate in the pathogenesis of IPF and may be a novel target for therapeutic intervention in this disease.

  13. Vascularization of the gray whale palate (Cetacea, Mysticeti, Eschrichtius robustus): soft tissue evidence for an alveolar source of blood to baleen.

    Science.gov (United States)

    Ekdale, Eric G; Deméré, Thomas A; Berta, Annalisa

    2015-04-01

    The origin of baleen in mysticetes heralded a major transition during cetacean evolution. Extant mysticetes are edentulous in adulthood, but rudimentary teeth develop in utero within open maxillary and mandibular alveolar grooves. The teeth are resorbed prenatally and the alveolar grooves close as baleen germ develops. Arteries supplying blood to highly vascularized epithelial tissue from which baleen develops pass through lateral nutrient foramina in the area of the embryonic alveolar grooves and rudimentary teeth. Those vessels are hypothesized to be branches of the superior alveolar artery, but branches of the greater palatine arteries may play a role in the baleen vascularization. Through a combination of latex injection, CT, and traditional dissection of the palate of a neonatal gray whale (Eschrichtius robustus), we confirm that the baleen receives blood from vessels within the superior alveolar canal via the lateral foramina. The greater palatine artery is restricted to its own passage with no connections to the baleen. This study has implications for the presence of baleen in extinct taxa by identifying the vessels and bony canals that supply blood to the epithelium from which baleen develops. The results indicate that the lateral foramina in edentulous mysticete fossils are bony correlates for the presence of baleen, and the results can be used to help identify bony canals and foramina that have been used to reconstruct baleen in extinct mysticetes that retained teeth in adulthood. Further comparisons are made with mammals that also possess oral keratin structures, including ruminants, ornithorhynchid monotremes, and sirenians. © 2015 Wiley Periodicals, Inc.

  14. PERFORATION OF INFERIOR ALVEOLAR NERVE BY MAXILLARY ARTERY. Perforation of inferior alveolar nerve by maxillary artery

    Directory of Open Access Journals (Sweden)

    Prakash B Billakanti

    2016-03-01

    Full Text Available La fosa infratemporal es un área anatómica clínicamente importante para la administración de agentes anestésicos locales en odontología y cirugía maxilofacial. Fueron estudiadas variaciones en la anatomía del nervio alveolar inferior y la arteria maxilar en la disección infratemporal. Durante la disección rutinaria de la cabeza en el cadáver de un varón adulto, fue observada una variación excepcional en el origen del nervio alveolar inferior y su relación con las estructuras circundantes. El nervio alveolar inferior se originaba en el nervio mandibular por dos raíces y la primera parte de la arteria maxilar estaba incorporada entre ambas. El origen embriológico de esta variación y sus implicaciones clínicas es debatido. Dado que la arteria maxilar transcurría entre las dos raíces del nervio alveolar inferior, y el nervio estaba fijado entre el foramen oval y el foramen mandibular, el atrapamiento vásculo-nervioso pudo causar entume-cimiento o dolor de cabeza e interferir con la inyección de anestésicos locales en la fosa infratemporal.  Variaciones anatómicas en esta región deben ser tenidas en cuenta, especialmente en casos de tratamiento fallido de neuralgia del trigémino. Infratemporal fossa is clinically important anatomical area for the delivery of local anesthetic agents in dentistry and maxillofacial surgery. Variations in the anatomy of the inferior alveolar nerve and maxillary artery were studied in infratemporal dissection. During routine dissection of the head in an adult male cadaver an unusual variation in the origin of the inferior alveolar nerve and its relationship with the surrounding structures was observed. The inferior alveolar nerve originated from the mandibular nerve by two roots and the first part of the maxillary artery was incorporated between them. An embryologic origin of this variation and its clinical implications is discussed. Because the maxillary artery runs between the two roots of

  15. Treatment of sharp mandibular alveolar process with hybrid prosthesis

    OpenAIRE

    Sukaedi, Sukaedi; Djulaeha, Eha

    2010-01-01

    Background: Losing posterior teeth for a long time would occasionally lead to the sharpening of alveolar process. The removable partial denture usually have problems when used during mastication, because of the pressure on the mucosa under the alveolar ridge. Purpose: The purpose of this case report was to manage patients with sharp mandibular alveolar process by wearing hybrid prosthesis with extra coronal precision attachment retention and soft liner on the surface base beneath the removabl...

  16. The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

    Science.gov (United States)

    Atochina-Vasserman, Elena N.; Massa, Christopher B.; Birkelbach, Bastian; Guo, Chang-Jiang; Scott, Pamela; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

    2015-01-01

    Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces. PMID:26320150

  17. Electrokinetic effects and fluid permeability

    International Nuclear Information System (INIS)

    Berryman, J.G.

    2003-01-01

    Fluid permeability of porous media depends mainly on connectivity of the pore space and two physical parameters: porosity and a pertinent length-scale parameter. Electrical imaging methods typically establish connectivity and directly measure electrical conductivity, which can then often be related to porosity by Archie's law. When electrical phase measurements are made in addition to the amplitude measurements, information about the pertinent length scale can then be obtained. Since fluid permeability controls the ability to flush unwanted fluid contaminants from the subsurface, inexpensive maps of permeability could improve planning strategies for remediation efforts. Detailed knowledge of fluid permeability is also important for oil field exploitation, where knowledge of permeability distribution in three dimensions is a common requirement for petroleum reservoir simulation and analysis, as well as for estimates on the economics of recovery

  18. Intranasal Fentanyl Intoxication Leading to Diffuse Alveolar Hemorrhage.

    Science.gov (United States)

    Ruzycki, Shannon; Yarema, Mark; Dunham, Michael; Sadrzadeh, Hossein; Tremblay, Alain

    2016-06-01

    Increasing rates of opioid abuse, particularly fentanyl, may lead to more presentations of unusual effects of opioid toxicity. Diffuse alveolar hemorrhage is a rare complication of fentanyl overdose. A 45-year-old male presented in hypoxic respiratory failure secondary to diffuse alveolar hemorrhage requiring intubation. Comprehensive drug screening detected fentanyl without exposure to cocaine. Further history upon the patient's recovery revealed exposure to snorted fentanyl powder immediately prior to presentation. Diffuse alveolar hemorrhage is a potential, though rare, presentation of opioid intoxication. Recognition of less common complications of opioid abuse such as diffuse alveolar hemorrhage is important in proper management of overdoses.

  19. Effect of permeability enhancers on paracellular permeability of acyclovir.

    Science.gov (United States)

    Ates, Muge; Kaynak, Mustafa Sinan; Sahin, Selma

    2016-06-01

    According to Biopharmaceutics Classification System (BCS), acyclovir is a class III (high solubility, low permeability) compound, and it is transported through paracellular route by passive diffusion. The aim of this study was to investigate the effect of various pharmaceutical excipients on the intestinal permeability of acyclovir. The single-pass in-situ intestinal perfusion (SPIP) method was used to estimate the permeability values of acyclovir and metoprolol across different intestinal segments (jejunum, ileum and colon). Permeability coefficient (Peff ) of acyclovir was determined in the absence and presence of a permeation enhancer such as dimethyl β-cyclodextrin (DM-β-CD), sodium lauryl sulfate (SLS), sodium caprate (Cap-Na) and chitosan chloride. All enhancers increased the permeability of paracellularly transported acyclovir. Although Cap-Na has the highest permeability-enhancing effect in all segments, permeation-enhancing effect of chitosan and SLS was only significant in ileum. On the other hand, DM-β-CD slightly decreased the permeability in all intestinal segments. These findings have potential implication concerning the enhancement of absorption of paracellularly transported compounds with limited oral bioavailability. In the case of acyclovir, Cap-Na either alone or in combination with SLS or chitosan has the potential to improve its absorption and bioavailability and has yet to be explored. © 2016 Royal Pharmaceutical Society.

  20. 3D-CT evaluation of secondary alveolar bone grafts in alveolar clefts

    Energy Technology Data Exchange (ETDEWEB)

    Naitoh, Hiroshi; Nishimura, Yoshihiko [Kyoto Univ. (Japan). Graduate School of Medicine; Yamawaki, Yoshiroh [Kyoto Katsura Hospital (Japan); Morimoto, Naoki [Kobe City General Hospital (Japan)

    2002-07-01

    From 1994 to 2000, we treated 116 patients with cleft alveolus by secondary alveolar bone grafts, and 48 of them were evaluated morphologically with 3D-CT. The frequency of successful bony bridging was significantly higher in the group whose grafts were completely enveloped (including the anterior alveolar ridge) with a mucoperiosteal flap. The frequency was also significantly higher in the group who underwent bone grafts at the age of 13 or less, and canine eruptions did not influence the ratio. Some cases showed such an improved growth pattern of grafted bone that the shape of the affected maxilla resembled that of the normal side, after long-term follow-up observations. The growth increment was remarkable in anterior maxillary height. Orthodontic management guides the canine or incisor into the reconstructed area of the previous cleft. We surmise that the new occlusal position puts pressure on the grafted bone and promotes further osteogenesis. These findings show that it is important to produce sufficient bony bridge to guide the canine or incisor, not the volume of grafted bone, in secondary alveolar bone grafts. Long-term follow-up observation, after more than 2-3 years, is also necessary to evaluate secondary alveolar bone grafts. (author)

  1. Permeability testing of biomaterial membranes

    Energy Technology Data Exchange (ETDEWEB)

    Dreesmann, L; Hajosch, R; Nuernberger, J Vaz; Schlosshauer, B [NMI Natural and Medical Sciences Institute at University Tuebingen, Markwiesenstr. 55, D-72770 Reutlingen (Germany); Ahlers, M [GELITA AG, Gammelsbacher Str. 2, D-69412 Eberbach (Germany)], E-mail: schlosshauer@nmi.de

    2008-09-01

    The permeability characteristics of biomaterials are critical parameters for a variety of implants. To analyse the permeability of membranes made from crosslinked ultrathin gelatin membranes and the transmigration of cells across the membranes, we combined three technical approaches: (1) a two-chamber-based permeability assay, (2) cell culturing with cytochemical analysis and (3) biochemical enzyme electrophoresis (zymography). Based on the diffusion of a coloured marker molecule in conjunction with photometric quantification, permeability data for a gelatin membrane were determined in the presence or absence of gelatin degrading fibroblasts. Cytochemical evaluation after cryosectioning of the membranes was used to ascertain whether fibroblasts had infiltrated the membrane inside. Zymography was used to investigate the potential release of proteases from fibroblasts, which are known to degrade collagen derivatives such as gelatin. Our data show that the diffusion equilibrium of a low molecular weight dye across the selected gelatin membrane is approached after about 6-8 h. Fibroblasts increase the permeability due to cavity formation in the membrane inside without penetrating the membrane for an extended time period (>21 days in vitro). Zymography indicates that cavity formation is most likely due to the secretion of matrix metalloproteinases. In summary, the combination of the depicted methods promises to facilitate a more rational development of biomaterials, because it provides a rapid means of determining permeability characteristics and bridges the gap between descriptive methodology and the mechanistic understanding of permeability alterations due to biological degradation.

  2. Permeability testing of biomaterial membranes

    International Nuclear Information System (INIS)

    Dreesmann, L; Hajosch, R; Nuernberger, J Vaz; Schlosshauer, B; Ahlers, M

    2008-01-01

    The permeability characteristics of biomaterials are critical parameters for a variety of implants. To analyse the permeability of membranes made from crosslinked ultrathin gelatin membranes and the transmigration of cells across the membranes, we combined three technical approaches: (1) a two-chamber-based permeability assay, (2) cell culturing with cytochemical analysis and (3) biochemical enzyme electrophoresis (zymography). Based on the diffusion of a coloured marker molecule in conjunction with photometric quantification, permeability data for a gelatin membrane were determined in the presence or absence of gelatin degrading fibroblasts. Cytochemical evaluation after cryosectioning of the membranes was used to ascertain whether fibroblasts had infiltrated the membrane inside. Zymography was used to investigate the potential release of proteases from fibroblasts, which are known to degrade collagen derivatives such as gelatin. Our data show that the diffusion equilibrium of a low molecular weight dye across the selected gelatin membrane is approached after about 6-8 h. Fibroblasts increase the permeability due to cavity formation in the membrane inside without penetrating the membrane for an extended time period (>21 days in vitro). Zymography indicates that cavity formation is most likely due to the secretion of matrix metalloproteinases. In summary, the combination of the depicted methods promises to facilitate a more rational development of biomaterials, because it provides a rapid means of determining permeability characteristics and bridges the gap between descriptive methodology and the mechanistic understanding of permeability alterations due to biological degradation

  3. Pre prosthetic reconstruction of alveolar ridge

    Directory of Open Access Journals (Sweden)

    Prabhuji Munivenkatappa Lakshmaiahenkatesh

    2011-01-01

    Full Text Available Dento-alveolar bony defects are common and occur due to a variety of causes, such as, pulpal pathology, traumatic tooth extraction, advanced periodontal disease, implant failure, tumor or congenital anomalies. These defects often cause a significant problem in dental treatment and rehabilitation. Many techniques exist for effective soft and hard tissue augmentation. The approach is largely based on the extent of the defect and specific procedures to be performed for the implant or prosthetic rehabilitation. This article presents case reports of soft and hard tissue ridge augmentation.

  4. Nostril Base Augmentation Effect of Alveolar Bone Graft

    Directory of Open Access Journals (Sweden)

    Woojin Lee

    2013-09-01

    Full Text Available Background The aims of alveolar bone grafting are closure of the fistula, stabilization ofthe maxillary arch, support for the roots of the teeth adjacent to the cleft on each side.We observed nostril base augmentation in patients with alveolar clefts after alveolar bonegrafting. The purpose of this study was to evaluate the nostril base augmentation effect ofsecondary alveolar bone grafting in patients with unilateral alveolar cleft.Methods Records of 15 children with alveolar clefts who underwent secondary alveolar bonegrafting with autogenous iliac cancellous bone between March of 2011 and May of 2012 werereviewed. Preoperative and postoperative worm’s-eye view photographs and reconstructedthree-dimensional computed tomography (CT scans were used for photogrammetry. Thedepression of the nostril base and thickness of the philtrum on the cleft side were measuredin comparison to the normal side. The depression of the cleft side pyriform aperture wasmeasured in comparison to the normal side on reconstructed three-dimensional CT.Results Significant changes were seen in the nostril base (P=0.005, the philtrum length(P=0.013, and the angle (P=0.006. The CT measurements showed significant changes in thepyriform aperture (P<0.001 and the angle (P<0.001.Conclusions An alveolar bone graft not only fills the gap in the alveolar process but alsoaugments the nostril base after surgery. In this study, only an alveolar bone graft was performedto prevent bias from other procedures. Nostril base augmentation can be achieved byperforming alveolar bone grafts in children, in whom invasive methods are not advised.

  5. Relative Permeability of Fractured Rock

    Energy Technology Data Exchange (ETDEWEB)

    Mark D. Habana

    2002-06-30

    Contemporary understanding of multiphase flow through fractures is limited. Different studies using synthetic fractures and various fluids have yielded different relative permeability-saturation relations. This study aimed to extend the understanding of multiphase flow by conducting nitrogen-water relative permeability experiments on a naturally-fractured rock from The Geysers geothermal field. The steady-state approach was used. However, steady state was achieved only at the endpoint saturations. Several difficulties were encountered that are attributed to phase interference and changes in fracture aperture and surface roughness, along with fracture propagation/initiation. Absolute permeabilities were determined using nitrogen and water. The permeability values obtained change with the number of load cycles. Determining the absolute permeability of a core is especially important in a fractured rock. The rock may change as asperities are destroyed and fractures propagate or st rain harden as the net stresses vary. Pressure spikes occurred in water a solute permeability experiments. Conceptual models of an elastic fracture network can explain the pressure spike behavior. At the endpoint saturations the water relative permeabilities obtained are much less than the nitrogen gas relative permeabilities. Saturations were determined by weighing and by resistivity calculations. The resistivity-saturation relationship developed for the core gave saturation values that differ by 5% from the value determined by weighing. Further work is required to complete the relative permeability curve. The steady-state experimental approach encountered difficulties due to phase interference and fracture change. Steady state may not be reached until an impractical length of time. Thus, unsteady-state methods should be pursued. In unsteady-state experiments the challenge will be in quantifying rock fracture change in addition to fluid flow changes.

  6. Bronchoalveolar permeability changes in rats inhaling gas/particle combinations during rest or exercise

    International Nuclear Information System (INIS)

    Bhalla, D.K.; Phalen, R.F.; Mannix, R.C.; Lavan, S.M.; Crocker, T.T.

    1986-01-01

    Bronchoalveolar (BA) injury in rats exposed at rest or exercise to air pollutants was studied by changes in epithelial permeability. Rats exposed to air, single gases or pollutant combinations were anesthetized, tracheostomized, and placed on an incline. /sup 99m/Tc-DTPA was delivered directly to a major bronchus. Radioactivity measurements were made on blood samples collected during first 10 min. Exposure of resting rats to 0.6 ppm O 3 increased BA permeability just after exposure, but it was normal 24 hrs later; in exercising rats the increase was greater than in rats exposed at rest, and it persisted up to 24 hrs. NO 2 at 6 ppm did not affect permeability. Exposure of resting rats to 2.5 ppm NO 2 + 0.6 ppm O 3 only increased permeability right after the exposure, but in exercising rats this exposure resulted in a greater permeability which remained elevated up to 24 hrs. Exposure of exercising rats to 0.8 ppm O 3 + 10 ppm HCHO increased permeability. Exposure of resting rats to an atmosphere of 0.6 ppm O 3 + 2.5 ppm NO 2 + 5 ppm SO 2 + 1 mg/m 3 sulfates of ferric, ammonium and manganese also produced an increase in permeability that persisted up to 24 hrs. The results suggest potentiation of the pollutant effects by exercise, but there is no indication of synergistic effect of pollutant combinations on BA permeability

  7. Alveolar macrophage phagocytosis is enhanced after blunt chest trauma and alters the posttraumatic mediator release.

    Science.gov (United States)

    Seitz, Daniel H; Palmer, Annette; Niesler, Ulrike; Fröba, Janine S; Heidemann, Vera; Rittlinger, Anne; Braumüller, Sonja T; Zhou, Shaoxia; Gebhard, Florian; Knöferl, Markus W

    2011-12-01

    Blunt chest trauma is known to induce a pulmonary invasion of short-lived polymorphonuclear neutrophils and apoptosis of alveolar epithelial type 2 (AT2) cells. Apoptotic cells are removed by alveolar macrophages (AMΦ). We hypothesized that chest trauma alters the phagocytic response of AMΦ as well as the mediator release of AMΦ during phagocytosis. To study this, male Sprague-Dawley rats were subjected to blunt chest trauma. Phagocytosis assays were performed in AMΦ isolated 2 or 24 h after trauma with apoptotic cells or opsonized beads. Phagocytosis of apoptotic AT2 cells by unstimulated AMΦ was significantly increased 2 h after trauma. At 24 h, AMΦ from traumatized animals, stimulated with phorbol-12-myristate-13-acetate, ingested significantly more apoptotic polymorphonuclear neutrophils than AMΦ from sham animals. Alveolar macrophages after trauma released significantly higher levels of tumor necrosis factor α, macrophage inflammatory protein 1α, and cytokine-induced neutrophil chemoattractant 1 when they incorporated latex beads, but significantly lower levels of interleukin 1β and macrophage inflammatory protein 1α when they ingested apoptotic cells. In vivo, phagocytosis of intratracheally instilled latex beads was decreased in traumatized rats. The bronchoalveolar lavage concentrations of the phagocytosis-supporting surfactant proteins A and D after blunt chest trauma were slightly decreased, whereas surfactant protein D mRNA expression in AT2 cells was significantly increased after 2 h. These findings indicate that chest trauma augments the phagocytosis of apoptotic cells by AMΦ. Phagocytosis of opsonized beads enhances and ingestion of apoptotic cells downregulates the immunologic response following lung contusion. Our data emphasize the important role of phagocytosis during posttraumatic inflammation after lung contusion.

  8. House dust mite allergen Der p 1 effects on sinonasal epithelial tight junctions.

    Science.gov (United States)

    Henriquez, Oswaldo A; Den Beste, Kyle; Hoddeson, Elizabeth K; Parkos, Charles A; Nusrat, Asma; Wise, Sarah K

    2013-08-01

    Epithelial permeability is highly dependent upon the integrity of tight junctions, which are cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer. Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen vs control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of TJPs was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total. Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1-exposed cultured sinonasal cells vs controls. Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis. © 2013 ARS-AAOA, LLC.

  9. House Dust Mite Der p 1 Effects on Sinonasal Epithelial Tight Junctions

    Science.gov (United States)

    Henriquez, Oswaldo A.; Beste, Kyle Den; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma; Wise, Sarah K.

    2013-01-01

    Background Epithelial permeability is highly dependent upon the integrity of tight junctions, cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer. Methods Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen versus control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of tight junction proteins was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total. Results Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1 exposed cultured sinonasal cells versus controls. Conclusion Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis. PMID:23592402

  10. Classification of alveolar bone destruction patterns on maxillary ...

    African Journals Online (AJOL)

    Objective: The defective diagnosis of alveolar structures is one of most serious handicaps when assessing available periodontal treatment options for the prevention of tooth loss. The aim of this research was to classify alveolar bone defects in the maxillary molar region which is a challenging area for dental implant ...

  11. Role of alveolar topology on acinar flows and convective mixing.

    Science.gov (United States)

    Hofemeier, Philipp; Sznitman, Josué

    2014-06-01

    Due to experimental challenges, computational simulations are often sought to quantify inhaled aerosol transport in the pulmonary acinus. Commonly, these are performed using generic alveolar topologies, including spheres, toroids, and polyhedra, to mimic the complex acinar morphology. Yet, local acinar flows and ensuing particle transport are anticipated to be influenced by the specific morphological structures. We have assessed a range of acinar models under self-similar breathing conditions with respect to alveolar flow patterns, convective flow mixing, and deposition of fine particles (1.3 μm diameter). By tracking passive tracers over cumulative breathing cycles, we find that irreversible flow mixing correlates with the location and strength of the recirculating vortex inside the cavity. Such effects are strongest in proximal acinar generations where the ratio of alveolar to ductal flow rates is low and interalveolar disparities are most apparent. Our results for multi-alveolated acinar ducts highlight that fine 1 μm inhaled particles subject to alveolar flows are sensitive to the alveolar topology, underlining interalveolar disparities in particle deposition patterns. Despite the simplicity of the acinar models investigated, our findings suggest that alveolar topologies influence more significantly local flow patterns and deposition sites of fine particles for upper generations emphasizing the importance of the selected acinar model. In distal acinar generations, however, the alveolar geometry primarily needs to mimic the space-filling alveolar arrangement dictated by lung morphology.

  12. A radiographic study of alveolar bone loss in Irish schoolchildren

    International Nuclear Information System (INIS)

    Buckley, L.A.

    1982-01-01

    Bitewing radiographs were used to assess evidence of alveolar bone loss in 1492 children in the age range 7-12 years. According to the method used in this study, alveolar bone loss was shown to occur in 1.7% of the children, and maxillary teeth were affected twice as frequently as mandibular teeth. (Author)

  13. Structural changes and effect of denopamine on alveolar fluid ...

    African Journals Online (AJOL)

    GREGORY

    2010-09-13

    Sep 13, 2010 ... alveolar fluid clearance in hypoxic rat lungs. Nai-jing Li1, Wei Li2, ... for absorption of excess alveolar fluid (Sartori et al.,. 2001 ... free access to food and water. ..... Dopamine increases lung liquid clearance during mechanical.

  14. Diffuse alveolar hemorrhage in a young woman with systemic lupus ...

    African Journals Online (AJOL)

    Diffuse Alveolar Hemorrhage (DAH) is rarely reported complication of Systemic Lupus Erythematosus (SLE). A young woman diagnosed SLE, with a previously normal plain chest radiograph, developed acute onset cough, dyspnoea and hemoptysis. The repeat urgent chest radiograph revealed alveolar opacities. The triad ...

  15. Enhancement and inhibition effects on the corneal permeability of timolol maleate: Polymers, cyclodextrins and chelating agents.

    Science.gov (United States)

    Rodríguez, Isabel; Vázquez, José Antonio; Pastrana, Lorenzo; Khutoryanskiy, Vitaliy V

    2017-08-30

    This study investigates how both bioadhesive polymers (chitosan, hyaluronic acid and alginate) and permeability enhancers (ethylene glycol- bis(2-aminoethylether)- N, N, N', N'- tetraacetic acid (EGTA) and hydroxypropyl-ß-cyclodextrin) influence the permeability of the anti-glaucoma drug timolol maleate through ex vivo bovine corneas. Our results showed that only the permeability enhancers alone were able to increase drug permeability, whereas the polymers significantly reduced drug permeation, and however, they increased the pre-corneal residence of timolol. Ternary systems (polymer-enhancer-drug) showed a reduced drug permeability compared to the polymers alone. Fluorescence microscopy analysis of the epithelium surface confirmed there was no evidence of epithelial disruption caused by these formulations, suggesting that polymer-enhancer interactions reduce drug solubilization and counteract the disruptive effect of the permeability enhancers on the surface of the cornea. Further mucoadhesive tests, revealed a stable interaction of chitosan and hyaluronic acid with the epithelium, while alginate showed poor mucoadhesive properties. The differences in mucoadhesion correlated with the permeability of timolol maleate observed, i.e. formulations containing mucoadhesive polymers showed lower drug permeabilities. The results of the present study indicate polymers acting as an additional barrier towards drug permeability which is even more evident in the presence of permeability enhancers like EGTA and hydroxypropyl-ß-cyclodextrin. Then, this study highlights the need to adequately select additives intended for ocular applications since interactions between them can have opposite results to what expected in terms of drug permeability. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Cultured fibroblasts from alveolar and gingival mucosae are biologically and biochemically different

    International Nuclear Information System (INIS)

    Lanz, J.; Banes, A.

    1986-01-01

    Tissues removed from the alveolar or gingival mucosa of 5 patients were separated into cell populations to assess the relative contributions each might make in wound healing intraorally. Growth curves and protein synthetic patterns of fibroblasts, free of epithelial cells, were obtained at pass 5. The morphologies of the two cell types were not grossly different. However, the AM cells (alveolar mucosa) had a generation time (gt) of 18.7 hrs. whereas the gt for KG cells (keratinized gingiva) was 49.6 hrs. Cells labeled in vitro with 35 S-methionine had distinct patterns of protein synthesis. The AM cells had more of the 275, 220, 92, 80, 50 and 46 kd bands on the autoradiogram of a 7.5% PAGE slab gel than did the KG cells. The KG cells contained more of the 165, 84, 68, 60, 54, 51, 43, 36, and 32a kd bands. In a wound healing situation, the AM cells may be the first fibroblasts to rapidly divide to fill a defect, whereas the KG cells may require a longer time period to divide. This is the first report of biochemical and biological differences in these two fibroblast populations from cultured, human tissues

  17. Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro

    International Nuclear Information System (INIS)

    Lipchik, R.J.; Chauncey, J.B.; Paine, R.; Simon, R.H.; Peters-Golden, M.

    1990-01-01

    Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung

  18. Geothermal Permeability Enhancement - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Joe Beall; Mark Walters

    2009-06-30

    The overall objective is to apply known permeability enhancement techniques to reduce the number of wells needed and demonstrate the applicability of the techniques to other undeveloped or under-developed fields. The Enhanced Geothermal System (EGS) concept presented in this project enhances energy extraction from reduced permeability zones in the super-heated, vapor-dominated Aidlin Field of the The Geysers geothermal reservoir. Numerous geothermal reservoirs worldwide, over a wide temperature range, contain zones of low permeability which limit the development potential and the efficient recovery of heat from these reservoirs. Low permeability results from poorly connected fractures or the lack of fractures. The Enhanced Geothermal System concept presented here expands these technologies by applying and evaluating them in a systematic, integrated program.

  19. Contemporary Approaches in the Repair of Alveolar Clefts

    Directory of Open Access Journals (Sweden)

    Ufuk Tatli

    2014-08-01

    Full Text Available Cleft lip and palate is one of the most common craniofacial anomalies. The repair of the alveolar clefts is an important part of the treatment for patients with cleft lip and palate. The treatment concepts of alveolar bone grafting are still controversial. The corresponding controversial issues are; timing of alveolar bone grafting, graft materials, and timing of the orthodontic expansion. In the present article, aforementioned controversial issues and contemporary treatment modalities of the maxillary alveolar clefts were reviewed in the light of current literature. In conclusion, the most suitable time for alveolar bone grafting is mixed dentition period. Grafting procedure may be performed in the early or late phases of this period depending on some clinical features. Adjunct orthodontic expansion procedures should be performed before and/or after grafting depending on the patient's current features. [Archives Medical Review Journal 2014; 23(4.000: 563-574

  20. Radiolabeled microsphere measurements of alveolar bone blood flow in dogs

    International Nuclear Information System (INIS)

    Kaplan, M.L.; Jeffcoat, M.K.; Goldhaber, P.

    1978-01-01

    Radiolabeled microspheres were injected into the left cardiac ventricle in healthy adult dogs to quantify blood in maxillary and mandibular alveolar bone. Heart rate, arterial blood pressure and pulse contour were monitored throughout each experiment. Blood flow in maxillary alveolar bone was more than 30 % greater (p<.001) than in mandibular alveolar bone. Alveolar bone blood flow (mean +- S.D.) measured as ml/min per gram was 0.12 +- .02 in the maxilla compared to 0.09 +- .02 in the mandible. The cardiovascular parameters monitored were constant immediately prior to the injection of microspheres and remained unchanged during and following injection. It is possible that radiolabeled microspheres can be used to quantify the circulatory changes in alveolar bone during the development of destructive periodontal disease in dogs. (author)

  1. Hydroxyapatite paste Ostim, without elevation of full-thickness flaps, improves alveolar healing stimulating BMP- and VEGF-mediated signal pathways: an experimental study in humans.

    Science.gov (United States)

    Canuto, R A; Pol, R; Martinasso, G; Muzio, G; Gallesio, G; Mozzati, M

    2013-08-01

    Tooth extraction is considered as the starting point of jaw atrophy via osteoclast activity stimulation. The maintenance of dental alveolar bone depends on surgery procedure and use of materials to maintain prior space favoring bone regeneration. Among substitutes used in dentistry to fill bone defects, Ostim-Pastes (Ostim) is a nanocrystalline paste tested for treatment of severe clinical conditions. This research first investigated the effect of Ostim on alveolar healing, comparing in the same healthy subjects, an Ostim-filled socket with a not-filled one. Moreover, it also proposed a new surgical protocol for the post-extractive socket treatment using the graft materials without elevation of full-thickness flaps. Fourteen patients were enrolled to bilateral maxillary or mandibular extraction that was performed without elevation of full-thickness flaps. In each patient, one socket was filled using Ostim, and the other one was allowed to undergo natural healing. No suture was carried out. Clinical and biologic parameters were screened at 1, 7, and 14 days. Obtained results evidenced that nanocrystalline hydroxyapatite supports bone regeneration, increasing the synthesis of pro-osteogenic factors as bone morphogenetics protein (BMP)-4, BMP-7, alkaline phosphatase, and osteocalcin. Moreover, filling post-extractive socket with nanocrystalline hydroxyapatite paste leads to a complete epithelialization already at 7 days after extraction, despite the fact that the teeth were extracted without elevation of full-thickness flaps . The improved epithelialization is mediated by increased vascular endothelial growth factor (VEGF) expression. No significant change was observed in inflammatory parameters, with exception of an early and transient IL-1β induction, that could trigger and improve alveolar healing. Clinical and biomolecular observations of this explorative study evidenced that nanocrystalline hydroxyapatite improves alveolar socket healing, increasing angiogenesis

  2. Clinical research on high oxygen permeable contact lens used after photorefractive keratectomy surgery

    Directory of Open Access Journals (Sweden)

    Hao-Jiang Yang

    2013-07-01

    Full Text Available AIM: To evaluate the outcome of high oxygen permeable contact lens used after photorefractive keratectomy(PRKsurgery.METHODS: Totally 95 patients(190 eyesafter PRK were included. Patients were randomly assigned to wear high oxygen permeable contact lens in one eye and normal lens in the fellow eye after surgery. The subjective symptoms and corneal epithelial status after PRK were evaluated. Uncorrected visual acuity(UCVAand haze were assessed at 6 months after PRK.RESULTS: Complaints of blurred vision, pain and photophobia were statistically more among the normal lens group than high oxygen permeable contact lens group(PPP=0.35. There was no difference in UCVA and haze 6 months after surgery(P=0.55. CONCLUSION: High oxygen permeable contact lens can significantly produce less the corneal irritated symptoms, reduce the discomfort feeling and promote healing of corneal epithelium after PRK.

  3. Permeability of cork to gases.

    Science.gov (United States)

    Faria, David P; Fonseca, Ana L; Pereira, Helen; Teodoro, Orlando M N D

    2011-04-27

    The permeability of gases through uncompressed cork was investigated. More than 100 samples were assessed from different plank qualities to provide a picture of the permeability distribution. A novel technique based on a mass spectrometer leak detector was used to directly measure the helium flow through the central area of small disks 10 mm in diameter and 2 mm thick. The permeability for nitrogen, oxygen, and other gases was measured by the pressure rise technique. Boiled and nonboiled cork samples from different sections were evaluated. An asymmetric frequency distribution ranging 3 orders of magnitude (roughly from 1 to 1000 μmol/(cm·atm·day)) for selected samples without macroscopic defects was found, having a peak below 100 μmol/(cm·atm·day). Correlation was found between density and permeability: higher density samples tend to show lower permeability. However, boiled cork showed a mean lower permeability despite having a lower density. The transport mechanism of gases through cork was also examined. Calculations suggest that gases permeate uncompressed cork mainly through small channels between cells under a molecular flow regime. The diameter of such channels was estimated to be in the range of 100 nm, in agreement with the plasmodesmata size in the cork cell walls.

  4. Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer

    International Nuclear Information System (INIS)

    Kamiya, Kenji; Yokoro, Kenjiro; Clifton, K.H.; Gould, M.N.

    1991-01-01

    We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: a) in the presence of E 2 and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, b) in cortisol deficient rats, Prl and E 2 synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, c) E 2 without progesterone stimulates alveolar colony formation in the presence of cortical and high Prl, d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E 2 , cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure. (author)

  5. Neutrophil migration through preexisting holes in the basal laminae of alveolar capillaries and epithelium during streptococcal pneumonia.

    Science.gov (United States)

    Walker, D C; Behzad, A R; Chu, F

    1995-11-01

    The purpose of this study was to determine whether or not there are preexisting holes in the endothelial and epithelial basal laminae of alveolar walls and to determine the path taken by neutrophils as they migrate from the capillaries to the airspace of the alveoli during inflammation. Using transmission electron microscopy and serial thin sections of normal rabbit and mouse lung, we have demonstrated the presence of slit-like holes in the capillary basal laminae and round holes in the basal laminae of type 2 pneumocytes. The slits in the capillary basal laminae were observed at the intersection of the thick and thin walls where endothelium, pericytes, and fibroblasts make close contact. The round holes in the type 2 cell basal laminae were observed at sites of close contact with fibroblasts. Neutrophils were observed to migrate through these slits and holes during streptococcal pneumonia in rabbit lungs. We conclude that during inflammation in the lung, migrating neutrophils displace pericytes and fibroblasts from the slits in the capillary basal lamina and then crawl through these slits into the alveolar interstitium. We postulate that neutrophils find their way to type 2 pneumocytes by following interstitial fibroblasts. We believe that neutrophils displace fibroblasts from their close contacts with the type 2 cells and then crawl through the holes in the basal lamina into the basal lateral space of the type 2 cells. From there, neutrophils migrate into the alveolar airspace.

  6. Interaction of the pathogenic mold Aspergillus fumigatus with lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Nir eOsherov

    2012-09-01

    Full Text Available Aspergillus fumigatus is an opportunistic environmental mold that can cause severe allergic responses in atopic individuals and poses a life-threatening risk for severely immunocompromised patients. Infection is caused by inhalation of fungal spores (conidia into the lungs. The initial point of contact between the fungus and the host is a monolayer of lung epithelial cells. Understanding how these cells react to fungal contact is crucial to elucidating the pathobiology of Aspergillus-related disease states. The experimental systems, both in vitro and in vivo, used to study these interactions, are described. Distinction is made between bronchial and alveolar epithelial cells. The experimental findings suggest that lung epithelial cells are more than just innocent bystanders or a purely physical barrier against infection. They can be better described as an active extension of our innate immune system, operating as a surveillance mechanism that can specifically identify fungal spores and activate an offensive response to block infection. This response includes the internalization of adherent conidia and the release of cytokines, antimicrobial peptides and reactive oxygen species. In the case of allergy, lung epithelial cells can dampen an over-reactive immune response by releasing anti-inflammatory compounds such as kinurenine. This review summarizes our current knowledge regarding the interaction of A. fumigatus with lung epithelial cells. A better understanding of the interactions between A. fumigatus and lung epithelial cells has therapeutic implications, as stimulation or inhibition of the epithelial response may alter disease outcome.

  7. Pulmonary and intestinal permeabilities in alcoholic hepatic cirrhosis

    International Nuclear Information System (INIS)

    De Botton, S.; Huglo, B.; Canva-Delacambre, V.; Colombel, J.F.; Beauchat, V.; Ziegels, P.; Prangere, T.; Steinling, M.; Machandise, X.; Wallaert, B.

    1997-01-01

    The aim of this prospective study was to evaluate simultaneously the intestinal permeability (IP), usually normal, and the pulmonary permeability, (PP) rather rarely studied, in patients afflicted with hepatic cirrhosis of alcoholic (HCA) origin. Thirty five non-smoker patients, afflicted with HCA, proved by biopsy, without pulmonary pathology and with normal pulmonary scanography were subject to our investigation. The pre-graft hepatic examination contained also respiratory functional explorations as well as bronchi-alveolar clearance (BAC) explorations. After inhalation of the DTPA- 99m Tc aerosols, a 20 min dynamical study in posterior-front condition was achieved. After exponential matching on the activity/time curve of the right lung, the half life (T 1/2 in min) and the Residual Activity at 10 min (RA in %) were calculated. The PI were than estimated and on the basis of urinary activity of EDTA- 51 Cr obtained on 24 h and expressed in % of the uptake activity, according to the Bjarnasson's technique. The results were compared (significant non-parametric tests if p 1/2 and 87.1% ± 6.7 vs 92.8% ± 2.6 (p < 0.002) for RA. It is significantly correlated with the total number of cells (r = -0.379) and with the number of lymphocytes (r = 0.351) in the BAC. For the first time an enhanced PP was observed in HCA, correlated with the increase in the number of cells at BAC

  8. Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

    OpenAIRE

    Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

    2013-01-01

    Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival sof...

  9. Bentonite Permeability at Elevated Temperature

    Directory of Open Access Journals (Sweden)

    Katherine A. Daniels

    2017-01-01

    Full Text Available Repository designs frequently favour geological disposal of radioactive waste with a backfill material occupying void space around the waste. The backfill material must tolerate the high temperatures produced by decaying radioactive waste to prevent its failure or degradation, leading to increased hydraulic conductivity and reduced sealing performance. The results of four experiments investigating the effect of temperature on the permeability of a bentonite backfill are presented. Bentonite is a clay commonly proposed as the backfill in repository designs because of its high swelling capacity and very low permeability. The experiments were conducted in two sets of purpose-built, temperature controlled apparatus, designed to simulate isotropic pressure and constant volume conditions within the testing range of 4–6 MPa average effective stress. The response of bentonite during thermal loading at temperatures up to 200 °C was investigated, extending the previously considered temperature range. The results provide details of bentonite’s intrinsic permeability, total stress, swelling pressure and porewater pressure during thermal cycles. We find that bentonite’s hydraulic properties are sensitive to thermal loading and the type of imposed boundary condition. However, the permeability change is not large and can mostly be accounted for by water viscosity changes. Thus, under 150 °C, temperature has a minimal impact on bentonite’s hydraulic permeability.

  10. Paracytosis of Haemophilus influenzae through cell layers of NCI-H292 lung epithelial cells

    NARCIS (Netherlands)

    van Schilfgaarde, M.; van Alphen, L.; Eijk, P.; Everts, V.; Dankert, J.

    1995-01-01

    Haemophilus influenzae penetrates the respiratory epithelium during carriage and invasive disease, including respiratory tract infections. We developed an in vitro model system consisting of lung epithelial NCI-H292 cells on permeable supports to study the passage of H. influenzae through lung

  11. Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.

    Science.gov (United States)

    Hasan, Djo; Blankman, Paul; Nieman, Gary F

    2017-09-01

    Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis.

  12. Permeability enhancement by shock cooling

    Science.gov (United States)

    Griffiths, Luke; Heap, Michael; Reuschlé, Thierry; Baud, Patrick; Schmittbuhl, Jean

    2015-04-01

    The permeability of an efficient reservoir, e.g. a geothermal reservoir, should be sufficient to permit the circulation of fluids. Generally speaking, permeability decreases over the life cycle of the geothermal system. As a result, is usually necessary to artificially maintain and enhance the natural permeability of these systems. One of the methods of enhancement -- studied here -- is thermal stimulation (injecting cold water at low pressure). This goal of this method is to encourage new thermal cracks within the reservoir host rocks, thereby increasing reservoir permeability. To investigate the development of thermal microcracking in the laboratory we selected two granites: a fine-grained (Garibaldi Grey granite, grain size = 0.5 mm) and a course-grained granite (Lanhelin granite, grain size = 2 mm). Both granites have an initial porosity of about 1%. Our samples were heated to a range of temperatures (100-1000 °C) and were either cooled slowly (1 °C/min) or shock cooled (100 °C/s). A systematic microstructural (2D crack area density, using standard stereological techniques, and 3D BET specific surface area measurements) and rock physical property (porosity, P-wave velocity, uniaxial compressive strength, and permeability) analysis was undertaken to understand the influence of slow and shock cooling on our reservoir granites. Microstructurally, we observe that the 2D crack surface area per unit volume and the specific surface area increase as a result of thermal stressing, and, for the same maximum temperature, crack surface area is higher in the shock cooled samples. This observation is echoed by our rock physical property measurements: we see greater changes for the shock cooled samples. We can conclude that shock cooling is an extremely efficient method of generating thermal microcracks and modifying rock physical properties. Our study highlights that thermal treatments are likely to be an efficient method for the "matrix" permeability enhancement of

  13. Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

    Science.gov (United States)

    Gon, Yasuhiro; Hashimoto, Shu

    2018-01-01

    Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Law, M.P.; Ahier, R.G.

    1989-01-01

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

  15. Nicotine transport in lung and non-lung epithelial cells.

    Science.gov (United States)

    Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

    2017-11-01

    Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Normal morphogenesis of epithelial tissues and progression of epithelial tumors

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

    2011-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

  17. Alveolar cleft closure with iliac bone graft: A case report.

    Directory of Open Access Journals (Sweden)

    Tichvy Tammama

    2017-04-01

    Conclusion: The timing of alveolar bone grafting usually associated with the state of the developing of dentition. Post operative management is important to get a good result, and to prevent any complications.

  18. Prevention of alveolar osteitis after third molar surgery: Comparative ...

    African Journals Online (AJOL)

    Prevention of alveolar osteitis after third molar surgery: Comparative study of the ... for surgical extraction of lower third molar were prospectively, consecutively, and ... Information on demographic, types and level of impaction, indications for ...

  19. Omphalocele and alveolar capillary dysplasia: a new association.

    NARCIS (Netherlands)

    Gerrits, L.C.; Mol, A.C. de; Bulten, J.; Staak, F.H.J.M. van der; Heijst, A.F.J. van

    2010-01-01

    OBJECTIVE: First report of an infant with coexistent omphalocele and alveolar capillary dysplasia. DESIGN: Descriptive case report. SETTING: Neonatal intensive care unit of a tertiary care children's hospital. PATIENT: We describe a term infant with omphalocele and respiratory insufficiency

  20. Alveolar distraction osteogenesis: revive and restore the native bone.

    Science.gov (United States)

    Sant, Sumedha; Jagtap, Amit

    2009-12-01

    In prosthodontics, knife-edge bony alveolar ridges can cause a problem in their rehabilitation. The distraction osteogenesis process raises the medullary component of the alveolus, allowing the labial plate of the existing natural bone to be displaced. This process involves mobilization, transport, and fixation of a healthy segment of bone adjacent to the deficient site. It entails use of the gradual controlled displacement of surgically created fractures, which results in simultaneous expansion of soft tissue and bone volume. A mechanical device, the alveolar distraction device, is used for this purpose. This modality of treatment can be used in implant dentistry cases for rehabilitation of resorbed ridges. The objective of this overview is to explain this procedure wherein the alveolar housing, including the osseous and soft-tissue components, is enlarged in a single, simultaneous process, which makes creation of an appropriate alveolar morphology possible.

  1. Probiotics promote endocytic allergen degradation in gut epithelial cells

    International Nuclear Information System (INIS)

    Song, Chun-Hua; Liu, Zhi-Qiang; Huang, Shelly; Zheng, Peng-Yuan; Yang, Ping-Chang

    2012-01-01

    Highlights: ► Knockdown of A20 compromised the epithelial barrier function. ► The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. ► Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. ► Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

  2. Probiotics promote endocytic allergen degradation in gut epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chun-Hua [Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou (China); Liu, Zhi-Qiang [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Huang, Shelly [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Zheng, Peng-Yuan, E-mail: medp7123@126.com [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Yang, Ping-Chang, E-mail: yangp@mcmaster.ca [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada)

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

  3. Alveolar lymphangioma in infants: report of two cases.

    LENUS (Irish Health Repository)

    FitzGerald, Kirsten

    2012-02-01

    The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children\\'s hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.

  4. Alveolar lymphangioma in infants: report of two cases.

    LENUS (Irish Health Repository)

    FitzGerald, Kirsten

    2009-06-01

    The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children\\'s hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.

  5. Dynamic thermal performance of alveolar brick construction system

    International Nuclear Information System (INIS)

    Gracia, A. de; Castell, A.; Medrano, M.; Cabeza, L.F.

    2011-01-01

    Highlights: → Even though U-value does not measure thermal inertia, it is the commonly used parameter. → The thermal performance analysis of buildings must include the evaluation of transient parameters. → Transient parameters of alveolar brick constructive system show good agreement with its low energy consumption. -- Abstract: Alveolar bricks are being introduced in building sector due to the simplicity of their construction system and to the elimination of the insulation material. Nevertheless, it is not clear if this new system is energetically efficient and which is its thermal behaviour. This paper presents an experimental and theoretical study to evaluate the thermal behaviour of the alveolar brick construction system, compared with a traditional Mediterranean brick system with insulation. The experimental study consists of measuring the thermal performance of four real house-like cubicles. The thermal transmittance in steady-state, also known as U-value, is calculated theoretically and experimentally for each cubicle, presenting the insulated cubicles as the best construction system, with differences around 45% in comparison to the alveolar one. On the other hand, experimental results show significantly smaller differences on the energy consumption between the alveolar and insulated construction systems during summer period (around 13% higher for the alveolar cubicle). These values demonstrate the high thermal efficiency of the alveolar system. In addition, the lack of agreement between the measured energy consumption and the calculated U-values, guides the authors to analyze the thermal inertia of the different building components. Therefore, several transient parameters, extracted from the heat transfer matrix and from experimental data, are also evaluated. It can be concluded that the alveolar brick construction system presents higher thermal inertia than the insulated one, justifying the low measured energy consumption.

  6. In Vitro Toxicity of Aluminum Nanoparticles in Rat Alveolar Macrophages

    Science.gov (United States)

    2006-03-01

    including intravenous, intramuscular , and subcutaneous injections, and including oral and ocular administration (Kreuter, 1991). NPs allow delivery of... NANOPARTICLES IN RAT ALVEOLAR MACROPHAGES THESIS Andrew J Wagner, 1st Lt, USAF AFIT/GES/ENV/06M-06 DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY ORCE...TOXICITY OF ALUMINUM NANOPARTICLES IN RAT ALVEOLAR MACROPHAGES THESIS Presented to the Faculty Department of Systems and Engineering

  7. Soft tissue healing in alveolar socket preservation technique: histologic evaluations.

    Science.gov (United States)

    Pellegrini, Gaia; Rasperini, Giulio; Obot, Gregory; Farronato, Davide; Dellavia, Claudia

    2014-01-01

    After tooth extraction, 14 alveolar sockets were grafted with porous bovine bone mineral particles and covered with non-cross-linked collagen membrane (test group), and 14 alveolar sockets were left uncovered. At 5 and 12 weeks, microvascular density (MVD), collagen content, and amount of lymphocytes (Lym) T and B were analyzed in soft tissue. At 5 weeks, MVD was significantly lower and Lym T was significantly higher in tests than in controls (P healing process of the soft tissue.

  8. A basic review on the inferior alveolar nerve block techniques

    OpenAIRE

    Khalil, Hesham

    2014-01-01

    The inferior alveolar nerve block is the most common injection technique used in dentistry and many modifications of the conventional nerve block have been recently described in the literature. Selecting the best technique by the dentist or surgeon depends on many factors including the success rate and complications related to the selected technique. Dentists should be aware of the available current modifications of the inferior alveolar nerve block techniques in order to effectively choose b...

  9. Alveolar ridge rehabilitation to increase full denture retention and stability

    OpenAIRE

    Mefina Kuntjoro; Rostiny Rostiny; Wahjuni Widajati

    2010-01-01

    Background: Atrophic mandibular alveolar ridge generally complicates prostetic restoration expecially full denture. Low residual alveolar ridge and basal seat can cause unstable denture, permanent ulcer, pain, neuralgia, and mastication difficulty. Pre-proshetic surgery is needed to improve denture retention and stability. Augmentation is a major surgery to increase vertical height of the atrophic mandible while vestibuloplasty is aimed to increase the denture bearing area. Purpose: The augme...

  10. Alveolar ridge augmentation by osteoinductive materials in goats

    DEFF Research Database (Denmark)

    Pinholt, E M; Haanaes, H R; Roervik, M

    1992-01-01

    The purpose of the present study was to determine whether alveolar ridge augmentation could be induced in goats. In 12 male goats allogenic, demineralized, and lyophilized dentin or bone was implanted subperiosteally on the buccal sides of the natural edentulous regions of the alveolar process...... of the mandible. Light microscopic evaluation revealed fibrous encapsulation, a few multinuclear giant cells, little inflammatory reaction, and no osteoinduction. It was concluded that no osteoinduction took place in goats....

  11. Cigarette smoke alters the secretome of lung epithelial cells.

    Science.gov (United States)

    Mossina, Alessandra; Lukas, Christina; Merl-Pham, Juliane; Uhl, Franziska E; Mutze, Kathrin; Schamberger, Andrea; Staab-Weijnitz, Claudia; Jia, Jie; Yildirim, Ali Ö; Königshoff, Melanie; Hauck, Stefanie M; Eickelberg, Oliver; Meiners, Silke

    2017-01-01

    Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease. Many of its more than 4500 chemicals are highly reactive, thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative MS to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix organization. In particular, secretion of secreted protein acidic and rich in cysteine, a matricellular protein that functions in tissue response to injury, was consistently diminished by cigarette smoke extract in various pulmonary epithelial cell lines and primary cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures. Our study reveals a previously unrecognized acute response of lung epithelial cells to cigarette smoke that includes altered secretion of proteins involved in extracellular matrix organization and wound healing. This may contribute to sustained alterations in tissue remodeling as observed in lung cancer and chronic obstructive pulmonary disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Horizontal alveolar bone loss: A periodontal orphan

    Science.gov (United States)

    Jayakumar, A.; Rohini, S.; Naveen, A.; Haritha, A.; Reddy, Krishnanjeneya

    2010-01-01

    Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician’s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs) (of patients diagnosed with chronic periodontitis and seeking periodontal care), which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm) or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36%) OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2%) teeth, and vertical defects were found only in 264 (7.8%) of the teeth, which was statistically significant (P<.001). Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3%) have addressed vertical bone loss, and 18 (3.7%) have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment modalities for

  13. Proximal alveolar bone loss in a longitudinal radiographic investigation

    International Nuclear Information System (INIS)

    Lavstvedt, S.; Bolin, A.; Henrikson, C.O.

    1986-01-01

    Four hundred and six individuals from an unselected sample from the County of Stockholm aged 18 to 65 years in 1970 were examined radiographically in 1970 and 1980. The differences in proximal alveolar bone height were recorded, attention being paid to the divergences in projection between the two investigations. The mean of the alveolar bone differnce was 5.5% of the mean root length, which corresponds to an average annual bone loss of 0.09 mm. Ninety per cent of the individuals had a difference in alveolar bone height of less than 10% of the root length, that is an average bone loss of 1.6 mm or less during 10 years. By linear regression analysis it was shown that the difference in alveolar bone height is a function of the initial bone loss; that is, the greater the initial bone loss, the greater the alveolar bone loss during the 10-year period. The result of the regression analysis may facilitate predictions of alveolar bone loss

  14. [Fatal alveolar haemorrhage following a "bang" of cannabis].

    Science.gov (United States)

    Grassin, F; André, M; Rallec, B; Combes, E; Vinsonneau, U; Paleiron, N

    2011-09-01

    The new methods of cannabis consumption (home made water pipe or "bang") may be responsible for fatal respiratory complications. We present a case, with fatal outcome, of a man of 19 years with no previous history other than an addiction to cannabis using "bang". He was admitted to intensive care with acute dyspnoea. A CT scan showed bilateral, diffuse alveolar shadowing. He was anaemic with an Hb of 9.3g/l. Bronchoalveolar lavage revealed massive alveolar haemorrhage. Investigations for infection and immunological disorder were negative and toxicology was negative except for cannabis. Antibiotic treatment was given and favourable progress allowed early discharge. Death occurred 15 days later due to alveolar haemorrhage following a further "bang" of cannabis. Autopsy showed toxic alveolar haemorrhage. The probable mechanism is pulmonary damage due to acid anhydrides released by the incomplete combustion of cannabis in contact with plastic. These acids have a double effect on the lungs: a direct toxicity with severe inflammation of the mucosa leading to alveolar haemorrhage and subsequently the acid anhydrides may lead to the syndrome of intra-alveolar haemorrhage and anaemia described in occupational lung diseases by Herbert in Oxford in 1979. It manifests itself by haemoptysis and intravascular haemolysis. We draw attention to the extremely serious potential consequences of new methods of using cannabis, particularly the use of "bang" in homemade plastic materials. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  15. Tritiated thymidine incorporation and the development of an interstitial lesion in the bronchiolar-alveolar regions of the lungs of normal and complement deficient mice after inhalation of chrysotile asbestos

    International Nuclear Information System (INIS)

    McGavran, P.D.; Butterick, C.J.; Brody, A.R.

    1989-01-01

    Inhaled asbestos causes the proliferation of bronchiolar-alveolar epithelial and interstitial cells in rats and mice 19 to 72 hours after a single 5-hour exposure. This condition is associated with rapid macrophage accumulation and development of an interstitial fibrotic lesion at alveolar duct bifurcations. In an attempt to define the mechanisms mediating asbestos-induced cell proliferation and fibrogenesis, we studied mice exposed to chrysotile asbestos for five hours. The mice were normal and a congenic strain (B10.D2/oSn), deficient in the fifth component of complement (C5-). We knew that the latter exhibit a depressed asbestos-induced macrophage response and wanted to learn whether the depressed response correlated with measurements of cell proliferation and progression of an interstitial lesion. Sections of first alveolar duct bifurcations were prepared for light microscopic autoradiography and ultrastructural morphometry at varying times after animal exposure to asbestos. In sham-exposed C5+ and C5- animals, less than 1% of epithelial and interstitial cells of the terminal bronchioles and alveolar ducts incorporated tritiated thymidine (3H-TdR) at any time after exposure to asbestos. Between 19 and 72 hours after exposure, epithelial and interstitial cells in both strains of mice exhibited significantly increased levels of 3H-TdR incorporation. The response decreased by eight days postexposure, and 3H-TdR incorporation was normal one month after exposure. Similarly, morphometry showed that both the C5+ and C5- asbestos-exposed mice exhibited significant increases in the volume density of epithelial and interstitial cells 48 hours after exposure. However, one month after exposure, the normal C5+ asbestos-exposed mice developed a fibrotic lesion, whereas the C5- asbestos-exposed animals were no different from sham-exposed C5- controls

  16. Alveolar socket healing: what can we learn?

    Science.gov (United States)

    Araújo, Mauricio G; Silva, Cléverson O; Misawa, Mônica; Sukekava, Flavia

    2015-06-01

    Tooth extraction induces a series of complex and integrated local changes within the investing hard and soft tissues. These local alterations arise in order to close the socket wound and to restore tissue homeostasis, and are referred to as '"socket healing". The aims of the present report were twofold: first, to describe the socket-healing process; and, second, to discuss what can be learned from the temporal sequence of healing events, in order to improve treatment outcomes. The socket-healing process may be divided into three sequential, and frequently overlapping, phases: inflammatory; proliferative; and modeling/remodeling. Several clinical and experimental studies have demonstrated that the socket-healing process promotes up to 50% reduction of the original ridge width, greater bone resorption at the buccal aspect than at the lingual/palatal counterpart and a larger amount of alveolar bone reduction in the molar region. In conclusion, tooth extraction, once a simple and straightforward surgical procedure, should be performed in the knowledge that ridge reduction will follow and that further clinical steps should be considered to compensate for this, when considering future options for tooth replacement. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

    Science.gov (United States)

    Liu, Xinxin; Zheng, Wei; Sivasankar, M Preeti

    2016-01-01

    Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3) expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001). Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (pacrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (pacrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium.

  18. Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

    Directory of Open Access Journals (Sweden)

    Richter Joachim

    2008-01-01

    Full Text Available Abstract Background Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells. Methods Rats were randomly assigned to a control, Celsior (CE or Celsior + surfactant (CE+S group (n = 5 each. In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4°C and 50 min of reperfusion at 37°C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups or immediately after sacrifice (Control, the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells. Results Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation: CE: 160 mm3 (0.61 vs. CE+S: 4 mm3 (0.75; p 3 (0.90 vs. CE+S: 0 mm3; p 3 (0.39 vs. CE+S: 268 mm3 (0.43; p 3(0.10 and CE+S (481 μm3(0.10 compared with controls (323 μm3(0.07; p Conclusion Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of

  19. Quantifying Evaporation in a Permeable Pavement System

    Science.gov (United States)

    Studies quantifying evaporation from permeable pavement systems are limited to a few laboratory studies and one field application. This research quantifies evaporation for a larger-scale field application by measuring the water balance from lined permeable pavement sections. Th...

  20. Permeable Pavement Research - Edison, New Jersey

    Science.gov (United States)

    This presentation provides the background and summary of results collected at the permeable pavement parking lot monitored at the EPA facility in Edison, NJ. This parking lot is surfaced with permeable interlocking concrete pavers (PICP), pervious concrete, and porous asphalt. ...

  1. Distracción osteogénica alveolar como método de aumento del reborde alveolar Alveolar osteogenic distraction as method to increase the alveolar ridge

    Directory of Open Access Journals (Sweden)

    Denia Morales Navarro

    2011-03-01

    Full Text Available La distracción osteogénica alveolar, como proceso biológico de neoformación de hueso alveolar, nos motivó a la realización de la presente revisión bibliográfica, con el objetivo enfatizar en el análisis de las variables: antecedentes históricos en Cuba, clasificación de los distractores, fases de la distracción (latencia, distracción y consolidación, indicaciones, contraindicaciones, ventajas, desventajas y complicaciones. Se realizó una revisión bibliográfica mediante la consulta de bases de datos de los sistemas referativos, como MEDLINE y PubMed con la utilización de descriptores "alveolar distraction" y "osteogenic distraction". Se consultaron las fuentes bibliográficas publicadas fundamentalmente en los últimos 5 años, lo que reveló que esta técnica es una excelente alternativa para la formación de huesos y tejidos blandos en zonas de atrofia alveolar, que consta de tres etapas: latencia, distracción y consolidación; un método previsible y con bajas tasas de reabsorción ósea en comparación con otras técnicas de aumento del reborde alveolar. Tiene su principal indicación en la terapia de implantes al proveer volumen óseo. Debemos individualizar cada caso y usar el método más adecuado según las características clínicas y personales del paciente. Una adecuada selección de los casos y una mejor comprensión de la técnica son los puntales para lograr exitosos resultados mediante la distracción osteogénica alveolar. En Cuba se ha aplicado poco la distracción alveolar, por lo que ha sido necesario ampliar los estudios sobre esta temática.The alveolar osteogenic distraction, as a biological process of alveolar bone neoformation, motivates us to make the bibliographic review whose objective was to emphasize in analysis the following variables: historical backgrounds in Cuba, distraction classification, distraction phases (latency, distraction and consolidation, indications, contraindications, advantages

  2. Quantifying porosity, compressibility and permeability in Shale

    DEFF Research Database (Denmark)

    Mbia, Ernest Ncha; Fabricius, Ida Lykke; Frykman, Peter

    strain data. We found that Kozeny's modelled permeability fall in the same order of magnitude with measured permeability for shale rich in kaolinite but overestimates permeability by two to three orders of magnitudes for shale with high content of smectite. The empirical Yang and Aplin model gives good...... permeability estimate comparable to the measured one for shale rich in smectite. This is probably because Yang and Aplin model was calibrated in London clay which is rich in smectite....

  3. Multifocal Epithelial Hyperplasia.

    Science.gov (United States)

    Agnew, Caitlin; Alexander, Sherene; Prabhu, Neeta

    2017-01-15

    Multifocal epithelial hyperplasia is a rare disease associated with human papilloma virus types 13 and 32. Diagnosis is based on clinical and histopathological findings, and most lesions are asymptomatic and regress spontaneously with time. The purpose of this paper is to describe a five-year-old girl who presented with multiple intraoral lesions on the buccal mucosa and tongue, which regressed spontaneously in 15 months.

  4. Possible links between intestinal permeablity and food processing: a potential therapeutic niche for glutamine

    Directory of Open Access Journals (Sweden)

    Jean Robert Rapin

    2010-01-01

    Full Text Available Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes.

  5. Possible Links between Intestinal Permeablity and Food Processing: A Potential Therapeutic Niche for Glutamine

    Science.gov (United States)

    Rapin, Jean Robert; Wiernsperger, Nicolas

    2010-01-01

    Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes. PMID:20613941

  6. Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte Activation

    DEFF Research Database (Denmark)

    Mitzscherling, Katja; Volynets, Valentina; Parlesak, Alexandr

    2009-01-01

    Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver disease (ALD......). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent transepithelial...... activation of human leukocytes. For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without the addition of CPBS (1.5 m...

  7. Phosphatidylcholine reverses ethanol-induced increase in transepithelial endotoxin permeability and abolishes transepithelial leukocyte activation

    DEFF Research Database (Denmark)

    Mitscherling, K.; Volynets, V.; Parlesak, Alexandr

    2009-01-01

    BACKGROUND: Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver...... disease (ALD). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent...... transepithelial activation of human leukocytes. METHODS: For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without...

  8. Gene expression profiles of human dendritic cells interacting with Aspergillus fumigatus in a bilayer model of the alveolar epithelium/endothelium interface.

    Directory of Open Access Journals (Sweden)

    Charles Oliver Morton

    Full Text Available The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549 and endothelium (human pulmonary artery epithelial cells, HPAEC on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC, monocyte-derived DC (moDC and myeloid DC (mDC, were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA.

  9. Partial pulmonary embolization disrupts alveolarization in fetal sheep

    Directory of Open Access Journals (Sweden)

    Hooper Stuart B

    2010-04-01

    Full Text Available Abstract Background Although bronchopulmonary dysplasia is closely associated with an arrest of alveolar development and pulmonary capillary dysplasia, it is unknown whether these two features are causally related. To investigate the relationship between pulmonary capillaries and alveolar formation, we partially embolized the pulmonary capillary bed. Methods Partial pulmonary embolization (PPE was induced in chronically catheterized fetal sheep by injection of microspheres into the left pulmonary artery for 1 day (1d PPE; 115d gestational age; GA or 5 days (5d PPE; 110-115d GA. Control fetuses received vehicle injections. Lung morphology, secondary septal crests, elastin, collagen, myofibroblast, PECAM1 and HIF1α abundance and localization were determined histologically. VEGF-A, Flk-1, PDGF-A and PDGF-Rα mRNA levels were measured using real-time PCR. Results At 130d GA (term ~147d, in embolized regions of the lung the percentage of lung occupied by tissue was increased from 29 ± 1% in controls to 35 ± 1% in 1d PPE and 44 ± 1% in 5d PPE fetuses (p VEGF and Flk-1, although a small increase in PDGF-Rα expression at 116d GA, from 1.00 ± 0.12 in control fetuses to 1.61 ± 0.18 in 5d PPE fetuses may account for impaired differentiation of alveolar myofibroblasts and alveolar development. Conclusions PPE impairs alveolarization without adverse systemic effects and is a novel model for investigating the role of pulmonary capillaries and alveolar myofibroblasts in alveolar formation.

  10. Viscous fingering with permeability heterogeneity

    International Nuclear Information System (INIS)

    Tan, C.; Homsy, G.M.

    1992-01-01

    Viscous fingering in miscible displacements in the presence of permeability heterogeneities is studied using two-dimensional simulations. The heterogeneities are modeled as stationary random functions of space with finite correlation scale. Both the variance and scale of the heterogeneities are varied over modest ranges. It is found that the fingered zone grows linearly in time in a fashion analogous to that found in homogeneous media by Tan and Homsy [Phys. Fluids 31, 1330 (1988)], indicating a close coupling between viscous fingering on the one hand and flow through preferentially more permeable paths on the other. The growth rate of the mixing zone increases monotonically with the variance of the heterogeneity, as expected, but shows a maximum as the correlation scale is varied. The latter is explained as a ''resonance'' between the natural scale of fingers in homogeneous media and the correlation scale

  11. Vacuolar ATPase regulates surfactant secretion in rat alveolar type II cells by modulating lamellar body calcium.

    Directory of Open Access Journals (Sweden)

    Narendranath Reddy Chintagari

    2010-02-01

    Full Text Available Lung surfactant reduces surface tension and maintains the stability of alveoli. How surfactant is released from alveolar epithelial type II cells is not fully understood. Vacuolar ATPase (V-ATPase is the enzyme responsible for pumping H(+ into lamellar bodies and is required for the processing of surfactant proteins and the packaging of surfactant lipids. However, its role in lung surfactant secretion is unknown. Proteomic analysis revealed that vacuolar ATPase (V-ATPase dominated the alveolar type II cell lipid raft proteome. Western blotting confirmed the association of V-ATPase a1 and B1/2 subunits with lipid rafts and their enrichment in lamellar bodies. The dissipation of lamellar body pH gradient by Bafilomycin A1 (Baf A1, an inhibitor of V-ATPase, increased surfactant secretion. Baf A1-stimulated secretion was blocked by the intracellular Ca(2+ chelator, BAPTA-AM, the protein kinase C (PKC inhibitor, staurosporine, and the Ca(2+/calmodulin-dependent protein kinase II (CaMKII, KN-62. Baf A1 induced Ca(2+ release from isolated lamellar bodies. Thapsigargin reduced the Baf A1-induced secretion, indicating cross-talk between lamellar body and endoplasmic reticulum Ca(2+ pools. Stimulation of type II cells with surfactant secretagogues dissipated the pH gradient across lamellar bodies and disassembled the V-ATPase complex, indicating the physiological relevance of the V-ATPase-mediated surfactant secretion. Finally, silencing of V-ATPase a1 and B2 subunits decreased stimulated surfactant secretion, indicating that these subunits were crucial for surfactant secretion. We conclude that V-ATPase regulates surfactant secretion via an increased Ca(2+ mobilization from lamellar bodies and endoplasmic reticulum, and the activation of PKC and CaMKII. Our finding revealed a previously unrealized role of V-ATPase in surfactant secretion.

  12. The global burden of alveolar echinococcosis.

    Directory of Open Access Journals (Sweden)

    Paul R Torgerson

    Full Text Available BACKGROUND: Human alveolar echinococcosis (AE is known to be common in certain rural communities in China whilst it is generally rare and sporadic elsewhere. The objective of this study was to provide a first estimate of the global incidence of this disease by country. The second objective was to estimate the global disease burden using age and gender stratified incidences and estimated life expectancy with the disease from previous results of survival analysis. Disability weights were suggested from previous burden studies on echinococcosis. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a detailed review of published literature and data from other sources. We were unable to make a standardised systematic review as the quality of the data was highly variable from different countries and hence if we had used uniform inclusion criteria many endemic areas lacking data would not have been included. Therefore we used evidence based stochastic techniques to model uncertainty and other modelling and estimating techniques, particularly in regions where data quality was poor. We were able to make an estimate of the annual global incidence of disease and annual disease burden using standard techniques for calculation of DALYs. Our studies suggest that there are approximately 18,235 (CIs 11,900-28,200 new cases of AE per annum globally with 16,629 (91% occurring in China and 1,606 outside China. Most of these cases are in regions where there is little treatment available and therefore will be fatal cases. Based on using disability weights for hepatic carcinoma and estimated age and gender specific incidence we were able to calculate that AE results in a median of 666,434 DALYs per annum (CIs 331,000-1.3 million. CONCLUSIONS/SIGNIFICANCE: The global burden of AE is comparable to several diseases in the neglected tropical disease cluster and is likely to be one of the most important diseases in certain communities in rural China on the Tibetan plateau.

  13. Cediranib for Metastatic Alveolar Soft Part Sarcoma

    Science.gov (United States)

    Kummar, Shivaani; Allen, Deborah; Monks, Anne; Polley, Eric C.; Hose, Curtis D.; Ivy, S. Percy; Turkbey, Ismail B.; Lawrence, Scott; Kinders, Robert J.; Choyke, Peter; Simon, Richard; Steinberg, Seth M.; Doroshow, James H.; Helman, Lee

    2013-01-01

    Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib. PMID:23630200

  14. Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

    Directory of Open Access Journals (Sweden)

    Dagmar A. Kuhn

    2014-09-01

    Full Text Available Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1 and a human alveolar epithelial type II cell line (A549. In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis. Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line.

  15. Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

    DEFF Research Database (Denmark)

    Jung, A; Allen, L; Nyengaard, Jens Randel

    2005-01-01

    Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have......, but the mean volume of a single lamellar body remains constant. These results demonstrate that chronic deficiency of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism. The design-based stereological approach...

  16. Regional alveolar partial pressure of oxygen measurement with parallel accelerated hyperpolarized gas MRI.

    Science.gov (United States)

    Kadlecek, Stephen; Hamedani, Hooman; Xu, Yinan; Emami, Kiarash; Xin, Yi; Ishii, Masaru; Rizi, Rahim

    2013-10-01

    Alveolar oxygen tension (Pao2) is sensitive to the interplay between local ventilation, perfusion, and alveolar-capillary membrane permeability, and thus reflects physiologic heterogeneity of healthy and diseased lung function. Several hyperpolarized helium ((3)He) magnetic resonance imaging (MRI)-based Pao2 mapping techniques have been reported, and considerable effort has gone toward reducing Pao2 measurement error. We present a new Pao2 imaging scheme, using parallel accelerated MRI, which significantly reduces measurement error. The proposed Pao2 mapping scheme was computer-simulated and was tested on both phantoms and five human subjects. Where possible, correspondence between actual local oxygen concentration and derived values was assessed for both bias (deviation from the true mean) and imaging artifact (deviation from the true spatial distribution). Phantom experiments demonstrated a significantly reduced coefficient of variation using the accelerated scheme. Simulation results support this observation and predict that correspondence between the true spatial distribution and the derived map is always superior using the accelerated scheme, although the improvement becomes less significant as the signal-to-noise ratio increases. Paired measurements in the human subjects, comparing accelerated and fully sampled schemes, show a reduced Pao2 distribution width for 41 of 46 slices. In contrast to proton MRI, acceleration of hyperpolarized imaging has no signal-to-noise penalty; its use in Pao2 measurement is therefore always beneficial. Comparison of multiple schemes shows that the benefit arises from a longer time-base during which oxygen-induced depolarization modifies the signal strength. Demonstration of the accelerated technique in human studies shows the feasibility of the method and suggests that measurement error is reduced here as well, particularly at low signal-to-noise levels. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

  17. [Alveolar ventilation and recruitment under lung protective ventilation].

    Science.gov (United States)

    Putensen, Christian; Muders, Thomas; Kreyer, Stefan; Wrigge, Hermann

    2008-11-01

    Goal of mechanical ventilation is to improve gas exchange and reduce work of breathing without contributing to further lung injury. Besides providing adequate EELV and thereby arterial oxygenation PEEP in addition to a reduction in tidal volume is required to prevent cyclic alveolar collapse and tidal recruitment and hence protective mechanical ventilation. Currently, there is no consensus if and if yes at which price alveolar recruitment with high airway pressures should be intended ("open up the lung"), or if it is more important to reduce the mechanical stress and strain to the lungs as much as possible ("keep the lung closed"). Potential of alveolar recruitment differs from patient to patient but also between lung regions. Potential for recruitment depends probably more on regional lung mechanics - especially on lung elastance - than on the underlying disease. Based on available data neither high PEEP nor other methods used for alveolar recruitment could demonstrate a survival benefit in patients with ARDS. These results may support an individualized titration of PEEP or other manoeuvres used for recruitment taking into consideration the regional effects. Bedside imaging techniques allowing titration of PEEP or other manoeuvres to prevent end-expiratory alveolar collapse (tidal recruitment) and inspiratory overinflation may be a promising development.

  18. A basic review on the inferior alveolar nerve block techniques.

    Science.gov (United States)

    Khalil, Hesham

    2014-01-01

    The inferior alveolar nerve block is the most common injection technique used in dentistry and many modifications of the conventional nerve block have been recently described in the literature. Selecting the best technique by the dentist or surgeon depends on many factors including the success rate and complications related to the selected technique. Dentists should be aware of the available current modifications of the inferior alveolar nerve block techniques in order to effectively choose between these modifications. Some operators may encounter difficulty in identifying the anatomical landmarks which are useful in applying the inferior alveolar nerve block and rely instead on assumptions as to where the needle should be positioned. Such assumptions can lead to failure and the failure rate of inferior alveolar nerve block has been reported to be 20-25% which is considered very high. In this basic review, the anatomical details of the inferior alveolar nerve will be given together with a description of its both conventional and modified blocking techniques; in addition, an overview of the complications which may result from the application of this important technique will be mentioned.

  19. Hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption.

    Science.gov (United States)

    Myrianthefs, Pavlos M; Briva, Arturo; Lecuona, Emilia; Dumasius, Vidas; Rutschman, David H; Ridge, Karen M; Baltopoulos, George J; Sznajder, Jacob Iasha

    2005-06-01

    Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO2 partial pressure (PCO2; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO2 higher than 30 mm Hg or metabolic alkalosis did not have an effect on this process. The hypocapnia-mediated decrease of alveolar fluid reabsorption was associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membranes of distal airspaces. The effect of low PCO2 on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO2 back to normal levels. These data suggest that hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption. Conceivably, correction of hypocapnic alkalosis in critically ill patients may contribute to the normalization of lung ability to clear edema.

  20. Region-specific role for Pten in maintenance of epithelial phenotype and integrity

    Science.gov (United States)

    Flodby, Per; Sunohara, Mitsuhiro; Castillo, Dan R.; McConnell, Alicia M.; Krishnaveni, Manda S.; Banfalvi, Agnes; Li, Min; Stripp, Barry; Zhou, Beiyun; Crandall, Edward D.; Minoo, Parviz

    2017-01-01

    Previous studies have demonstrated resistance to naphthalene-induced injury in proximal airways of mice with lung epithelial-specific deletion of the tumor-suppressor gene Pten, attributed to increased proliferation of airway progenitors. We tested effects of Pten loss following bleomycin injury, a model typically used to study distal lung epithelial injury, in conditional PtenSFTPC-cre knockout mice. Pten-deficient airway epithelium exhibited marked hyperplasia, particularly in small bronchioles and at bronchoalveolar duct junctions, with reduced E-cadherin and β-catenin expression between cells toward the luminal aspect of the hyperplastic epithelium. Bronchiolar epithelial and alveolar epithelial type II (AT2) cells in PtenSFTPC-cre mice showed decreased expression of epithelial markers and increased expression of mesenchymal markers, suggesting at least partial epithelial-mesenchymal transition at baseline. Surprisingly, and in contrast to previous studies, mutant mice were exquisitely sensitive to bleomycin, manifesting rapid weight loss, respiratory distress, increased early mortality (by day 5), and reduced dynamic lung compliance. This was accompanied by sloughing of the hyperplastic airway epithelium with occlusion of small bronchioles by cellular debris, without evidence of increased parenchymal lung injury. Increased airway epithelial cell apoptosis due to loss of antioxidant defenses, reflected by decreased expression of superoxide dismutase 3, in combination with deficient intercellular adhesion, likely predisposed to airway sloughing in knockout mice. These findings demonstrate an important role for Pten in maintenance of airway epithelial phenotype integrity and indicate that responses to Pten deletion in respiratory epithelium following acute lung injury are highly context-dependent and region-specific. PMID:27864284

  1. Effect of aggregate grain size distribution on properties of permeable ...

    African Journals Online (AJOL)

    ) ratio on the mechanical properties of permeable concrete is investigated. The aim of this study is to prepare permeable concrete mixture with optimum properties in terms of strength and permeability. For this purpose, five different permeable ...

  2. Polarity in Mammalian Epithelial Morphogenesis

    OpenAIRE

    Roignot, Julie; Peng, Xiao; Mostov, Keith

    2013-01-01

    Cell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture model...

  3. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane

    Energy Technology Data Exchange (ETDEWEB)

    BARCELLOS-HOFF, M. H; AGGELER, J.; RAM, T. G; BISSELL, M. J

    1989-02-01

    An essential feature of mammary gland differentiation during pregnancy is the formation of alveoli composed of polarized epithelial cells, which, under the influence of lactogenic hormones, secrete vectorially and sequester milk proteins. Previous culture studies have described either organization of cells polarized towards lumina containing little or no demonstrable tissue-specific protein, or establishment of functional secretory cells exhibiting little or no glandular architecture. In this paper, we report that tissue-specific vectorial secretion coincides with the formation of functional alveoli-like structures by primary mammary epithelial cells cultured on a reconstituted basement membrane matrix (derived from Engelbreth-Holm-Swarm murine tumour). Morphogenesis of these unique three-dimensional structures was initiated by cell-directed remodelling of the exogenous matrix leading to reorganization of cells into matrixensheathed aggregates by 24 h after plating. The aggregates subsequently cavitated, so that by day 6 the cells were organized into hollow spheres in which apical cell surfaces faced lumina sealed by tight junctions and basal surfaces were surrounded by a distinct basal lamina. The profiles of proteins secreted into the apical (luminal) and basal (medium) compartments indicated that these alveoli-like structures were capable of an appreciable amount of vectorial secretion. Immunoprecipitation with a broad spectrum milk antiserum showed that more than 80% of caseins were secreted into the lumina, whereas iron-binding proteins (both lactoferrin and transferrin) were present in comparable amounts in each compartment. Thus, these mammary cells established protein targeting pathways directing milk-specific proteins to the luminal compartment. A time course monitoring secretory activity demonstrated that establishment of tissue-specific vectorial secretion and increased total and milk protein secretion coincided with functional alveolar

  4. The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae

    Science.gov (United States)

    Jagoe, R. Thomas; Jarman, Elizabeth R.; North, James C.; Pridmore, Alison; Musaya, Janelisa; French, Neil; Zijlstra, Eduard E.; Molyneux, Malcolm E.; Read, Robert C.

    2013-01-01

    We tested the hypothesis that HIV infection results in activation of alveolar macrophages and that this might be associated with impaired defense against pneumococcus. We compared alveolar macrophages and lymphocytes in 131 bronchoalveolar lavage samples from HIV-infected and healthy controls using inflammatory gene microarrays, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA) to determine the pattern of macrophage activation associated with HIV infection and the effect of this activation on defense against pneumococcus. We used gamma interferon (IFN-γ) priming to mimic the cellular milieu in HIV-infected lungs. InnateDB and BioLayout 3D were used to analyze the interactions of the upregulated genes. Alveolar macrophages from HIV-infected adults showed increased gene expression and cytokine production in a classical pattern. Bronchoalveolar lavage from HIV-infected subjects showed excess CD8+ lymphocytes with activated phenotype. Toll-like receptor 4 (TLR4) expression was increased in macrophages from HIV-infected subjects, but function was similar between the groups; lung lavage fluid did not inhibit TLR function in transfected HeLa cells. Alveolar macrophages from HIV-infected subjects showed normal binding and internalization of opsonized pneumococci, with or without IFN-γ priming. Alveolar macrophages from HIV-infected subjects showed classical activation compared to that of healthy controls, but this does not alter macrophage interactions with pneumococci. PMID:23576675

  5. Dressing for alveolopalatal wounds after alveolar bone grafting.

    Science.gov (United States)

    Kondoh, Shoji; Matsuo, Kiyoshi; Yuzuriha, Shunsuke; Kikuchi, Nirou; Ban, Ryokuya

    2003-09-01

    Cotton gauze with alpha cyanoacrylate was used for alveolopalatal wound dressing after alveolar bone grafting to treat 93 alveolar clefts in 74 cleft patients to reduce mechanical injuries, tension for wound dehiscence, and adhesion of food remnants. T-shaped cotton gauze was put on the gingivoperiosteal flaps and was impregnated with cyanoacrylate. The procedure required no preoperative preparation and its intraoperative execution took less than 5 minutes. The gauze with cyanoacrylate was removed approximately 1 week after surgery. No infection was observed at any of the operational sites, but tiny fistulas developed at four of them. The mean bone graft score was 1.4 point. No complications such as thermal injury resulted from the use of cyanoacrylate. Gauze impregnated with cyanoacrylate proved to be a convenient and dependable dressing for alveolopalatal wounds resulting from gingivoperiosteoplasty for alveolar bone grafting.

  6. Peripheral epithelial odontogenic tumor

    International Nuclear Information System (INIS)

    Carzoglio, J.; Tancredi, N.; Capurro, S.; Ravecca, T.; Scarrone, P.

    2006-01-01

    A new case of peripheral epithelial odontogenic tumor (Pindborg tumor) is reported. It is localized in the superior right gingival region, a less frequent site, and has the histopathological features previously reported. Immunochemical studies were performed, revealing a differential positive stain to cytokeratins in tumor cells deeply seated in the tumor mass, probably related to tumoral cell heterogeneity.Interestingly, in this particular case S-100 protein positive reactivity was also detected in arborescent cells intermingled with tumoral cells, resembling Langerhans cells. Even though referred in the literature in central Pindborg tumors, no references were found about their presence in peripheral tumors, like the one that is presented here

  7. Human corneal epithelial subpopulations

    DEFF Research Database (Denmark)

    Søndergaard, Chris Bath

    2013-01-01

    Corneal epithelium is being regenerated throughout life by limbal epithelial stem cells (LESCs) believed to be located in histologically defined stem cell niches in corneal limbus. Defective or dysfunctional LESCs result in limbal stem cell deficiency (LSCD) causing pain and decreased visual acuity...... subpopulations in human corneal epithelium using a combination of laser capture microdissection and RNA sequencing for global transcriptomic profiling. We compared dissociation cultures, using either expansion on γ-irradiated NIH/3T3 feeder cells in serum-rich medium or expansion directly on plastic in serum...

  8. De novo expression of sodium-glucose cotransporter SGLT2 in Bowman’s capsule coincides with replacement of parietal epithelial cell layer with proximal tubule-like epithelium

    OpenAIRE

    Tabatabai, Niloofar M.; North, Paula E.; Regner, Kevin R.; Kumar, Suresh N.; Duris, Christine B.; Blodgett, Amy B.

    2014-01-01

    In kidney nephron, parietal epithelial cells line the Bowman’s capsule and function as a permeability barrier for the glomerular filtrate. Bowman’s capsule cells with proximal tubule epithelial morphology have been found. However, the effects of tubular metaplasia in Bowman’s capsule on kidney function remain poorly understood. Sodium-glucose cotransporter 2 (SGLT2) plays a major role in reabsorption of glucose in the kidney and is expressed on brush border membrane of epithelial cells in the...

  9. Disrupted epithelial/macrophage crosstalk via Spinster homologue 2-mediated S1P signaling may drive defective macrophage phagocytic function in COPD.

    Directory of Open Access Journals (Sweden)

    Hai B Tran

    Full Text Available We have previously established a link between impaired phagocytic capacity and deregulated S1P signaling in alveolar macrophages from COPD subjects. We hypothesize that this defect may include a disruption of epithelial-macrophage crosstalk via Spns2-mediated intercellular S1P signaling.Primary alveolar macrophages and bronchial epithelial cells from COPD subjects and controls, cell lines, and a mouse model of chronic cigarette smoke exposure were studied. Cells were exposed to 10% cigarette smoke extract, or vehicle control. Spns2 expression and subcellular localization was studied by immunofluorescence, confocal microscopy and RT-PCR. Phagocytosis was assessed by flow-cytometry. Levels of intra- and extracellular S1P were measured by S1P [3H]-labeling.Spns2 expression was significantly increased (p<0.05 in alveolar macrophages from current-smokers/COPD patients (n = 5 compared to healthy nonsmokers (n = 8 and non-smoker lung transplant patients (n = 4. Consistent with this finding, cigarette smoke induced a significant increase in Spns2 expression in both human alveolar and THP-1 macrophages. In contrast, a remarkable Spns2 down-regulation was noted in response to cigarette smoke in 16HBE14o- cell line (p<0.001 in 3 experiments, primary nasal epithelial cells (p<0.01 in 2 experiments, and in smoke-exposed mice (p<0.001, n = 6 animals per group. Spns2 was localized to cilia in primary bronchial epithelial cells. In both macrophage and epithelial cell types, Spns2 was also found localized to cytoplasm and the nucleus, in line with a predicted bipartile Nuclear Localization Signal at the position aa282 of the human Spns2 sequence. In smoke-exposed mice, alveolar macrophage phagocytic function positively correlated with Spns2 protein expression in bronchial epithelial cells.Our data suggest that the epithelium may be the major source for extracellular S1P in the airway and that there is a possible disruption of epithelial/macrophage cross talk via

  10. Hard and Soft Tissue Management of a Localized Alveolar Ridge Atrophy with Autogenous Sources and Biomaterials: A Challenging Clinical Case

    Directory of Open Access Journals (Sweden)

    C. Maiorana

    2016-01-01

    Full Text Available Particularly in the premaxillary area, the stability of hard and soft tissues plays a pivotal role in the success of the rehabilitation from both a functional and aesthetic aspect. The present case report describes the clinical management of a localized alveolar ridge atrophy in the area of the upper right canine associated with a thin gingival biotype with a lack of keratinized tissue. An autogenous bone block harvested from the chin associated with heterologous bone particles was used to replace the missing bone, allowing for a prosthetic driven implant placement. Soft tissues deficiency was corrected by means of a combined epithelialized and subepithelial connective tissue graft. The 3-year clinical and radiological follow-up demonstrated symmetric gingival levels of the upper canines, with physiological peri-implant probing depths and bone loss. Thus, the use of autogenous tissues combined with biomaterials might be considered a reliable technique in case of highly aesthetic demanding cases.

  11. Reconstruction of alveolar defects in patients with cleft lip and palate - 111 consecutive patients

    DEFF Research Database (Denmark)

    Andersen, Kristian

    2012-01-01

    Reconstruction of alveolar defects in patients with cleft lip and palate - 111 consecutive patients......Reconstruction of alveolar defects in patients with cleft lip and palate - 111 consecutive patients...

  12. Secondary bone grafting for alveolar cleft in children with cleft lip or cleft lip and palate

    NARCIS (Netherlands)

    Guo, J.; Li, C.; Zhang, Q.; Wu, G.; Deacon, S.A.; Chen, J.; Hu, H.; Zou, S.; Ye, Q.

    2011-01-01

    BACKGROUND: Secondary alveolar bone grafting has been widely used to reconstruct alveolar cleft. However, there is still some controversy. OBJECTIVES: To compare the effectiveness and safety of different secondary bone grafting methods. SEARCH STRATEGY: The final electronic and handsearches were

  13. Permeability of highly compacted bentonite

    International Nuclear Information System (INIS)

    Pusch, R.

    1980-12-01

    The object of the study was the water flow through the bentonite which is caused by hydraulic gradients. The study comprised laboratory tests and theoretical considerations. It was found that high bulk densities reduced the permeability to very low values. It was concluded that practically impervious conditions prevail when the gradients are low. Thus with a regional gradient of 10 -2 and a premeability of 10 -13 m/s the flow rate will not be higher than approximately 1 mm in 30 000 years. (G.B.)

  14. Proximal alveolar bone loss in a longitudinal radiographic investigation

    International Nuclear Information System (INIS)

    Bolin, A.; Lavstedt, S.; Henrikson, C.O.; Frithiof, L.

    1986-01-01

    The difference in proximal alveolar bone height between 1970 and 1980, the ''ABD index'', has been measured longitudinally in radiographs from an unselected material. The group constitutes 406 individuals born in 1904 - 1952 in the county of Stockholm. 13 of 18 predictors determined in 1970 were significantly related to the ABD index in the simple correlation analyses. The predictor ''the alveolar bone loss 1970'' (ABL index 1970) had the strongest correlation to the ABD index. In the stepwise multiple regression analysis the predictor ABL index 1970 and three other predictors reached significant levels. These were age, number of lost teeth and Russell's Periodontal Index

  15. Alveolar ridge rehabilitation to increase full denture retention and stability

    Directory of Open Access Journals (Sweden)

    Mefina Kuntjoro

    2010-12-01

    Full Text Available Background: Atrophic mandibular alveolar ridge generally complicates prostetic restoration expecially full denture. Low residual alveolar ridge and basal seat can cause unstable denture, permanent ulcer, pain, neuralgia, and mastication difficulty. Pre-proshetic surgery is needed to improve denture retention and stability. Augmentation is a major surgery to increase vertical height of the atrophic mandible while vestibuloplasty is aimed to increase the denture bearing area. Purpose: The augmentation and vestibuloplasty was aimed to provide stability and retentive denture atrophic mandibular alveolar ridge. Case: A 65 years old woman patient complained about uncomfortable denture. Clinical evaluate showed flat ridge in the anterior mandible, flabby tissue and candidiasis, while residual ridge height was classified into class IV. Case management: Augmentation using autograph was conducted as the mandible vertical height is less than 15 mm. Autograph was used to achieve better bone quantity and quality. Separated alveolar ridge was conducted from left to right canine region and was elevated 0.5 mm from the previous position to get new ridge in the anterior region. The separated alveolar ridge was fixated by using T-plate and ligature wire. Three months after augmentation fixation appliances was removed vestibuloplasty was performed to increase denture bearing area that can make a stable and retentive denture. Conclusion: Augmentation and vestibuloplasty can improve flat ridge to become prominent.Latar belakang: Ridge mandibula yang atrofi pada umumnya mempersulit pembuatan restorasi prostetik terutama gigi tiruan lengkap (GTL. Residual alveolar ridge dan basal seat yang rendah menyebabkan gigi tiruan menjadi tidak stabil, menimbulkan ulser permanen, nyeri, neuralgia, dan kesulitan mengunyah. Tujuan: Augmentasi dan vestibuloplasti pada ridge mandibula yang atrofi dilakukan untuk menciptakan gigi tiruan yang stabil dan retentive. Kasus: Pasien wanita

  16. Autoradiographic study of the permeability characteristics of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Kingham, J G.C.; Baker, J H; Loehry, C A [Royal Victoria Hospital, Bournemouth (UK)

    1978-02-01

    This autoradiographic study demonstrates the distribution of a range of small solutes and macromolecules in the mucosa of the guinea-pig small intestine after intracardiac injection. The substances investigated were: /sup 14/C-urea, /sup 3/H-mannose, /sup 3/H-inulin, and /sup 125/I polyvinylpyrrolidone (PVP). Small bowel biopsies were taken at intervals from one to 60 minutes after injection and the tissues processed for autoradiography. Light microscopic examination of the autoradiographs showed that the compartmental distribution depended on the molecular size of the substances being studied. Urea and mannose, as small solutes, were uniformly distributed throughout the intravascular, extravascular, and epithelial compartments. Inulin was evenly distributed in the vessel lumen and extravascular space but there was a considerable drop in concentration in the epithelium. PVP exhibited the most marked gradients, the concentration being greatest in the vascular lumina, lower in the extravascular space, least in the epithelium. Thus there appear to be two barriers to macromolecular passage which are freely permeable to small solutes: the capillary wall and the epithelium. At a light microscopical level it was not possible to observe whether the limiting membrane of each of these barriers is the cell plasmalemmal membrane or the basement membrane. The selectivity of the epithelial barrier was greater than that of the capillary barrier.

  17. Epithelial Cell Cultures

    Directory of Open Access Journals (Sweden)

    Imran S. Chaudhry

    2011-01-01

    Full Text Available The biological effects of only a finite number of tobacco toxins have been studied. Here, we describe exposure of cultures of human bronchial epithelial cells to low concentrations of tobacco carcinogens: nickel sulphate, benzo(bfluoranthene, N-nitrosodiethylamine, and 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK. After a 24-hour exposure, EGFR was expressed in cell membrane and cytoplasm, BCL-2 was expressed only in the irregular nuclei of large atypical cells, MKI67 was expressed in nuclei with no staining in larger cells, cytoplasmic BIRC5 with stronger nuclear staining was seen in large atypical cells, and nuclear TP53 was strongly expressed in all cells. After only a 24-hour exposure, cells exhibited atypical nuclear and cytoplasmic features. After a 48-hour exposure, EGFR staining was localized to the nucleus, BCL-2 was slightly decreased in intensity, BIRC5 was localized to the cytoplasm, and TP53 staining was increased in small and large cells. BCL2L1 was expressed in both the cytoplasm and nuclei of cells at 24- and 48-hour exposures. We illustrate that short-termexposure of a bronchial epithelial cell line to smoking-equivalent concentrations of tobacco carcinogens alters the expression of key proliferation regulatory genes, EGFR, BCL-2, BCL2L1, BIRC5, TP53, and MKI67, similar to that reported in biopsy specimens of pulmonary epithelium described to be preneoplastic lesions.

  18. Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease: Role of Cigarette Smoke Exposure.

    Science.gov (United States)

    Aghapour, Mahyar; Raee, Pourya; Moghaddam, Seyed Javad; Hiemstra, Pieter S; Heijink, Irene H

    2018-02-01

    The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.

  19. Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury.

    Science.gov (United States)

    Proper, Steven P; Saini, Yogesh; Greenwood, Krista K; Bramble, Lori A; Downing, Nathaniel J; Harkema, Jack R; Lapres, John J

    2014-02-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2α(Δ/Δ)) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2α(Δ/Δ) mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2α(Δ/Δ) and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung.

  20. Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

    OpenAIRE

    Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

    2013-01-01

    Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infectio...

  1. Mobility of macrophages and alveolar decontamination in different kinds of animals

    Energy Technology Data Exchange (ETDEWEB)

    Nolibe, D; Metivier, H; Masse, R

    1973-05-01

    From congress on alveolar macrophage; Lille, France (28 May The mobility of macrophages in relation to alveolar decontamination following the inhalation of toxic substances was studied in the dog, monkey, cat, rat, and guinea pig. The alveolar macroPhages showed a migration rate that varied from 30 to 10% in the rat and rabbit. The measurement of alveolar decontamination should take into consideration inter-species differences in macrophage mobility. (JSR)

  2. Functional and structural alterations of epithelial barrier properties of rat ileum following X-irradiation

    International Nuclear Information System (INIS)

    Dublineau, I.; Lebrun, F.; Grison, S.; Griffiths, N.M.

    2004-01-01

    Irradiation of the digestive system leads to alterations of the small intestine. We have characterized the disruption of the barrier integrity in rat ileum from 1 to 14 days following irradiation ranging from 6 to 12 Gy. The intestinal permeability to 14 C-mannitol and 3 H-dextran 70,000 was measured in vitro in Ussing chambers. In parallel to these functional studies, immunohistochemical analyses of junctional proteins (ZO-1 and β-catenin) of ileal epithelium were performed by confocal microscopy. Irradiation with 10 Gy induced a marked decrease in epithelial tissue resistance at three days and a fivefold increase in mannitol permeability, without modifications of dextran permeability. A disorganization of the localization for ZO-1 and β-catenin was also observed. At 7 days after irradiation, we observed a recovery of the organization of junctional proteins in parallel to a return of intestinal permeability to control value. In addition to these time-dependent effects, a gradual effect on epithelial integrity of the radiation doses was observed 3 days after irradiation. This study shows a disruption of the integrity of the intestinal barrier in rat ileum following abdominal X-irradiation, depending on the time postirradiation and on the delivered dose. The loss of barrier integrity was characterized by a disorganization of proteins of tight and adherent junctions, leading to increased intestinal permeability to mannitol. (author)

  3. The world of epithelial sheets.

    Science.gov (United States)

    Honda, Hisao

    2017-06-01

    An epithelium is a layer of closely connected cells covering the body or lining a body cavity. In this review, several fundamental questions are addressed regarding the epithelium. (i) While an epithelium functions as barrier against the external environment, how is barrier function maintained during its construction? (ii) What determines the apical and basal sides of epithelial layer? (iii) Is there any relationship between the apical side of the epithelium and the apical membrane of an epithelial cell? (iv) Why are hepatocytes (liver cells) called epithelial, even though they differ completely from column-like shape of typical epithelial cells? Keeping these questions in mind, multiple shapes of epithelia were considered, extracting a few of their elemental processes, and constructing a virtual world of epithelia by combining them. Epithelial cells were also classified into several types based on the number of apical domains of each cell. In addition, an intracellular organelle was introduced within epithelial cells, the vacuolar apical compartment (VAC), which is produced within epithelial cells surrounded by external cell matrix (ECM). The VAC interacts with areas of cell-cell contact of the cell surface membrane and is converted to apical membrane. The properties of VACs enable us to answer the initial questions posed above. Finally, the genetic and molecular mechanisms of epithelial morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

  4. Steam-water relative permeability

    Energy Technology Data Exchange (ETDEWEB)

    Ambusso, W.; Satik, C.; Home, R.N. [Stanford Univ., CA (United States)

    1997-12-31

    A set of relative permeability relations for simultaneous flow of steam and water in porous media have been measured in steady state experiments conducted under the conditions that eliminate most errors associated with saturation and pressure measurements. These relations show that the relative permeabilities for steam-water flow in porous media vary approximately linearly with saturation. This departure from the nitrogen/water behavior indicates that there are fundamental differences between steam/water and nitrogen/water flows. The saturations in these experiments were measured by using a high resolution X-ray computer tomography (CT) scanner. In addition the pressure gradients were obtained from the measurements of liquid phase pressure over the portions with flat saturation profiles. These two aspects constitute a major improvement in the experimental method compared to those used in the past. Comparison of the saturation profiles measured by the X-ray CT scanner during the experiments shows a good agreement with those predicted by numerical simulations. To obtain results that are applicable to general flow of steam and water in porous media similar experiments will be conducted at higher temperature and with porous rocks of different wetting characteristics and porosity distribution.

  5. DMPD: Silica binding and toxicity in alveolar macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18226603 Silica binding and toxicity in alveolar macrophages. Hamilton RF Jr, Thaku...l) Show Silica binding and toxicity in alveolar macrophages. PubmedID 18226603 Title Silica binding and toxicity in alveolar macropha...ges. Authors Hamilton RF Jr, Thakur SA, Holian A. Public

  6. Clogging in permeable concrete: A review.

    Science.gov (United States)

    Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

    2017-05-15

    Permeable concrete (or "pervious concrete" in North America) is used to reduce local flooding in urban areas and is an important sustainable urban drainage system. However, permeable concrete exhibits reduction in permeability due to clogging by particulates, which severely limits service life. This paper reviews the clogging mechanism and current mitigating strategies in order to inform future research needs. The pore structure of permeable concrete and characteristics of flowing particulates influence clogging, which occurs when particles build-up and block connected porosity. Permeable concrete requires regular maintenance by vacuum sweeping and pressure washing, but the effectiveness and viability of these methods is questionable. The potential for clogging is related to the tortuosity of the connected porosity, with greater tortuosity resulting in increased potential for clogging. Research is required to develop permeable concrete that can be poured on-site, which produces a pore structure with significantly reduced tortuosity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Different Methods of Predicting Permeability in Shale

    DEFF Research Database (Denmark)

    Mbia, Ernest Ncha; Fabricius, Ida Lykke; Krogsbøll, Anette

    by two to five orders of magnitudes at lower vertical effective stress below 40 MPa as the content of clay minerals increases causing heterogeneity in shale material. Indirect permeability from consolidation can give maximum and minimum values of shale permeability needed in simulating fluid flow......Permeability is often very difficult to measure or predict in shale lithology. In this work we are determining shale permeability from consolidation tests data using Wissa et al., (1971) approach and comparing the results with predicted permeability from Kozeny’s model. Core and cuttings materials...... effective stress to 9 μD at high vertical effective stress of 100 MPa. The indirect permeability calculated from consolidation tests falls in the same magnitude at higher vertical effective stress, above 40 MPa, as that of the Kozeny model for shale samples with high non-clay content ≥ 70% but are higher...

  8. CCAAT/enhancer binding protein beta (C/EBPβ) isoform balance as a regulator of epithelial-mesenchymal transition in mouse mammary epithelial cells

    International Nuclear Information System (INIS)

    Miura, Yuka; Hagiwara, Natsumi; Radisky, Derek C.; Hirai, Yohei

    2014-01-01

    Activation of the epithelial-mesenchymal transition (EMT) program promotes cell invasion and metastasis, and is reversed through mesenchymal-epithelial transition (MET) after formation of distant metastases. Here, we show that an imbalance of gene products encoded by the transcriptional factor C/EBPβ, LAP (liver-enriched activating protein) and LIP (liver-enriched inhibitory protein), can regulate both EMT- and MET-like phenotypic changes in mouse mammary epithelial cells. By using tetracycline repressive LIP expression constructs, we found that SCp2 cells, a clonal epithelial line of COMMA1-D cells, expressed EMT markers, lost the ability to undergo alveolar-like morphogenesis in 3D Matrigel, and acquired properties of benign adenoma cells. Conversely, we found that inducible expression of LAP in SCg6 cells, a clonal fibroblastic line of COMMA1-D cells, began to express epithelial keratins with suppression of proliferation. The overexpression of the C/EBPβ gene products in these COMMA1-D derivatives was suppressed by long-term cultivation on tissue culture plastic, but gene expression was maintained in cells grown on Matrigel or exposed to proteasome inhibitors. Thus, imbalances of C/EBPβ gene products in mouse mammary epithelial cells, which are affected by contact with basement membrane, are defined as a potential regulator of metastatic potential. - Highlights: • We created a temporal imbalance of C/EBPβ gene products in the mammary model cells. • The temporal up-regulation of LIP protein induced EMT-like cell behaviors. • The temporal up-regulation of LAP protein induced MET-like cell behaviors. • Excess amount of C/EBPβ gene products were eliminated by proteasomal-degradation. • Basement membrane components attenuated proteasome-triggered protein elimination

  9. Intestinal infection with Giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion.

    Science.gov (United States)

    Scott, Kevin G-E; Meddings, Jonathon B; Kirk, David R; Lees-Miller, Susan P; Buret, André G

    2002-10-01

    Giardiasis causes malabsorptive diarrhea, and symptoms can be present in the absence of any significant morphologic injury to the intestinal mucosa. The effects of giardiasis on epithelial permeability in vivo remain unknown, and the role of T cells and myosin light chain kinase (MLCK) in altered intestinal barrier function is unclear. This study was conducted to determine whether Giardia spp. alters intestinal permeability in vivo, to assess whether these abnormalities are dependent on T cells, and to assess the role of MLCK in altered epithelial barrier function. Immunocompetent and isogenic athymic mice were inoculated with axenic Giardia muris trophozoites or sterile vehicle (control), then assessed for trophozoite colonization and gastrointestinal permeability. Mechanistic studies using nontransformed human duodenal epithelial monolayers (SCBN) determined the effects of Giardia on myosin light chain (MLC) phosphorylation, transepithelial fluorescein isothiocyanate-dextran fluxes, cytoskeletal F-actin, tight junctional zonula occludens-1 (ZO-1), and MLCK. Giardia infection caused a significant increase in small intestinal, but not gastric or colonic, permeability that correlated with trophozoite colonization in both immunocompetent and athymic mice. In vitro, Giardia increased permeability and phosphorylation of MLC and reorganized F-actin and ZO-1. These alterations were abolished with an MLCK inhibitor. Disruption of small intestinal barrier function is T cell independent, disappears on parasite clearance, and correlates with reorganization of cytoskeletal F-actin and tight junctional ZO-1 in an MLCK-dependent fashion.

  10. Buccal Infiltration versus Inferior Alveolar Nerve Block in Mandibular ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... Purpose: The purpose of this study is to compare the success rates of inferior alveolar nerve block (IANB) and buccal infiltration anesthesia of mandibular second premolar with irreversible pulpitis and to evaluate the level of patient discomfort with these methods. Matherials and Methods: Forty patients, who.

  11. Correlation between alveolar ventilation and electrical properties of lung parenchyma.

    Science.gov (United States)

    Roth, Christian J; Ehrl, Andreas; Becher, Tobias; Frerichs, Inéz; Schittny, Johannes C; Weiler, Norbert; Wall, Wolfgang A

    2015-06-01

    One key problem in modern medical imaging is linking measured data and actual physiological quantities. In this article we derive such a link between the electrical bioimpedance of lung parenchyma, which can be measured by electrical impedance tomography (EIT), and the magnitude of regional ventilation, a key to understanding lung mechanics and developing novel protective ventilation strategies. Two rat-derived three-dimensional alveolar microstructures obtained from synchrotron-based x-ray tomography are each exposed to a constant potential difference for different states of ventilation in a finite element simulation. While the alveolar wall volume remains constant during stretch, the enclosed air volume varies, similar to the lung volume during ventilation. The enclosed air, serving as insulator in the alveolar ensemble, determines the resulting current and accordingly local tissue bioimpedance. From this we can derive a relationship between lung tissue bioimpedance and regional alveolar ventilation. The derived relationship shows a linear dependence between air content and tissue impedance and matches clinical data determined from a ventilated patient at the bedside.

  12. Pulmonary scan in evaluating alveolar-interstitial syndrome in ER

    Directory of Open Access Journals (Sweden)

    Giovanni Volpicelli

    2006-10-01

    Full Text Available Diffuse comet-tail artifacts at lung ultrasound are due to thickened interlobular septa and extravascular lung water. This condition is typical of the alveolar-interstitial syndrome due to pulmonary edema, diffuse parenchymal lung disease or ARDS. Aim of our study is to assess the potential of bedside lung ultrasound to diagnose the alveolar-interstitial syndrome in patients admitted to our emergency medicine unit. The ultrasonic feature of multiple and diffuse comet-tail artifacts was investigated during 5 months, in 121 consecutive patients admitted to our unit. Each patient was studied bedside in a supine position, by 8 antero-lateral pulmonary intercostal scans. Ultrasonic results were compared with chest radiograph and clinical outcome. Lung ultrasound showed a sensitivity of 84% and a specificity of 98% in diagnosing the radiologic alveolar-interstitial syndrome. Corresponding figures in the identification of a disease involving lung interstitium were 83% and 96%. These preliminary data show that the study of comet-tail artifacts at lung ultrasound is a method reasonably accurate for diagnosing the alveolar-interstitial syndrome at bedside. This conclusion opens the hypothesis of the usefullness of bedside lung ultrasound in the evaluation of dyspnoeic patients in the emergency setting.

  13. Sensitivity of MRI in detecting alveolar infiltrates. Experimental studies

    International Nuclear Information System (INIS)

    Biederer, J.; Busse, I.; Grimm, J.; Reuter, M.; Heller, M.; Muhle, C.; Freitag, S.

    2002-01-01

    Purpose: An experimental study using porcine lung explants and a dedicated chest phantom to evaluate the signal intensity of artificial alveolar infiltrates with T 1 - and T 2 -weighted MRI sequences. Material and Methods: 10 porcine lung explants were intubated, transferred into the cavity of a MRI-compatible chest phantom and inflated by continuous evacuation of the artificial pleural space. All lungs were examined with MRI at 1.5 T before and after intra-tracheal instillation of either 100 or 200 ml gelatine-stabilised liquid to simulate alveolar infiltrates. MR-examination comprised gradient echo (2D- and 3D-GRE) and fast spin echo sequences (T 2 -TSE and T 2 -HASTE). The signal intensity of lung parenchyma was evaluated at representative cross sections using a standardised scheme. Control studies were acquired with helical CT. Results: The instilled liquid caused patchy confluent alveolar infiltrates resembling the findings in patients with pneumonia or ARDS. CT revealed typical ground-glass opacities. Before the application of the liquid, only T 2 -HASTE and T 2 -TSE displayed lung parenchyma signals with a signal/noise ratio of 3.62 and 1.39, respectively. After application of the liquid, both T 2 -weighted sequences showed clearly visible infiltrates with an increase in signal intensity of approx. 30% at 100 ml (p 2 -weighted sequences detects artificial alveolar infiltrates with high signal intensity and may be a highly sensitive tool to detect pneumonia in patients. (orig.) [de

  14. Mechanisms of alveolar fibrosis after acute lung injury.

    Science.gov (United States)

    Marinelli, W A; Henke, C A; Harmon, K R; Hertz, M I; Bitterman, P B

    1990-12-01

    In patients who die after severe acute lung injury, a dramatic fibroproliferative response occurs within the alveolar air space, interstitium, and microvessels. Profound shunt physiology, dead space ventilation, and pulmonary hypertension are the physiologic consequences of this fibroproliferative response. The anatomic pattern of the response is unique within each alveolar compartment. For example, the air space is obliterated by granulation tissue, with replicating mesenchymal cells, their connective tissue products, and an expanding network of intra-alveolar capillaries. In contrast, the vascular fibroproliferative response is dominated by mesenchymal cell replication and connective tissue deposition within the walls of microvessels. Despite the unique anatomic features of these fibroproliferative processes, the regulatory signals involved are likely to be similar. Although our current understanding of the signals regulating the fibroproliferative response to acute lung injury is limited, inferences can be made from in vitro studies of mesenchymal cell behavior and several better understood fibroproliferative processes, including wound healing and chronic fibrotic lung diseases. As clinicians, our future ability to enhance effective lung repair will likely utilize therapeutic strategies specifically targeted to the signals that regulate the fibroproliferative process within the alveolar microenvironment.

  15. Prevention of Alveolar Osteitis After Third Molar Surgery ...

    African Journals Online (AJOL)

    2017-05-16

    May 16, 2017 ... Nigerian Journal of Clinical Practice ¦ Volume 20 ¦ Issue 4 ¦ April 2017 observed similar percentages of alveolar osteitis using mouthwashes of warm saline and 0.2% chlorhexidine. (23.7% and 20.9%, respectively) in a randomized controlled study. The use of warm saline rinse is a common postextraction.

  16. Autochthonous human alveolar echinococcosis in a Hungarian patient.

    Science.gov (United States)

    Dezsényi, Balázs; Strausz, Tamás; Makrai, Zita; Csomor, Judit; Danka, József; Kern, Peter; Rezza, Giovanni; Barth, Thomas F E; Casulli, Adriano

    2017-02-01

    Alveolar echinococcosis is a zoonotic parasitic disease causing a severe clinical condition and is known as the most deadly of all helminth infections. Moreover, this disease is also an increasing concern in Northern and Eastern Europe due to its spread in the wildlife animal host. An asymptomatic 70-year-old woman from south-western Hungary was diagnosed with multiple liver lesions. Imaging techniques (ultrasound, computed tomography and magnetic resonance imaging), serology (ELISA, indirect hemagglutination and Western blot), and conventional staining methods (hematoxylin-eosin and periodic acid-Schiff) were used for the detection of the disease. A histopathological re-evaluation of formalin-fixed paraffin block by immunohistochemical staining with the monoclonal antibody Em2G11 definitively confirmed the diagnosis of alveolar echinococcosis. To our knowledge, this is the first confirmed autochthonous case of human alveolar echinococcosis in Hungary. To what extent diagnostic difficulties may contribute to underestimate this zoonosis in Eastern Europe is unknown. Differential diagnosis with alveolar echinococcosis should be considered for patients with multiple, tumor-like cystic lesions of the liver, in countries where this parasite is emerging.

  17. Alveolar Ridge Split Technique Using Piezosurgery with Specially Designed Tips

    Directory of Open Access Journals (Sweden)

    Alessandro Moro

    2017-01-01

    Full Text Available The treatment of patients with atrophic ridge who need prosthetic rehabilitation is a common problem in oral and maxillofacial surgery. Among the various techniques introduced for the expansion of alveolar ridges with a horizontal bone deficit is the alveolar ridge split technique. The aim of this article is to give a description of some new tips that have been specifically designed for the treatment of atrophic ridges with transversal bone deficit. A two-step piezosurgical split technique is also described, based on specific osteotomies of the vestibular cortex and the use of a mandibular ramus graft as interpositional graft. A total of 15 patients were treated with the proposed new tips by our department. All the expanded areas were successful in providing an adequate width and height to insert implants according to the prosthetic plan and the proposed tips allowed obtaining the most from the alveolar ridge split technique and piezosurgery. These tips have made alveolar ridge split technique simple, safe, and effective for the treatment of horizontal and vertical bone defects. Furthermore the proposed piezosurgical split technique allows obtaining horizontal and vertical bone augmentation.

  18. Alveolar Ridge Split Technique Using Piezosurgery with Specially Designed Tips.

    Science.gov (United States)

    Moro, Alessandro; Gasparini, Giulio; Foresta, Enrico; Saponaro, Gianmarco; Falchi, Marco; Cardarelli, Lorenzo; De Angelis, Paolo; Forcione, Mario; Garagiola, Umberto; D'Amato, Giuseppe; Pelo, Sandro

    2017-01-01

    The treatment of patients with atrophic ridge who need prosthetic rehabilitation is a common problem in oral and maxillofacial surgery. Among the various techniques introduced for the expansion of alveolar ridges with a horizontal bone deficit is the alveolar ridge split technique. The aim of this article is to give a description of some new tips that have been specifically designed for the treatment of atrophic ridges with transversal bone deficit. A two-step piezosurgical split technique is also described, based on specific osteotomies of the vestibular cortex and the use of a mandibular ramus graft as interpositional graft. A total of 15 patients were treated with the proposed new tips by our department. All the expanded areas were successful in providing an adequate width and height to insert implants according to the prosthetic plan and the proposed tips allowed obtaining the most from the alveolar ridge split technique and piezosurgery. These tips have made alveolar ridge split technique simple, safe, and effective for the treatment of horizontal and vertical bone defects. Furthermore the proposed piezosurgical split technique allows obtaining horizontal and vertical bone augmentation.

  19. Proximal alveolar bone loss in a longitudinal radiographic investigation

    International Nuclear Information System (INIS)

    Bolin, A.; Lavstedt, S.; Henrikson, C.O.; Frithiof, L.

    1986-01-01

    In Sweden people in all age groups now have more remaining teeth than previosly. An investigation has been made to identify some predictors of alveolar bone loss in a 10-year period in subjects with at least 20 remaining teeth. The material consisted of 349 individuals, examined radiographically, clinically and by interview in 1970 and in 1980. These subjects, born in 1904-1952, constituted a subgroup, with regard to remaining teeth, of an unselected sample of the population of the old county of Stockholm. In the unselected sample statistically significant predictors of alveolar bone loss found in a stepwise multiple regression analysis were 1) alveolar bone loss in 1970, 2) age, 3) number of lost teeth and 4) Russell's Periodontol Index (PI). In the subgroup the predictors were in the order 1) Russell's PI and 2) smoking. The prediction values (R 2 ) of further variables were marginal. The analyses showed that there was an interaction between PI and smoking, implying that the effect of smoking on alveolar bone loss was increased in individuals with high PI values. Furthermore, a tendency was found for a dose-response effect of tobacco consumption. This tendency almost disappeared when controlling for PI

  20. Pulmonary alveolar proteinosis in a child from an informal settlement

    African Journals Online (AJOL)

    Pulmonary alveolar proteinosis (PAP) is a syndrome characterised by respiratory failure caused by pulmonary surfactant accumulation and resulting in respiratory insu ciency and an increased incidence of infections.[1] e current standard therapy is whole- lung lavage, which is used to physically remove the accumulated.

  1. Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins

    NARCIS (Netherlands)

    Szafranski, P.; Gambin, T.; Dharmadhikari, A.V.; Akdemir, K.C.; Jhangiani, S.N.; Schuette, J.; Godiwala, N.; Yatsenko, S.A.; Sebastian, J.; Madan-Khetarpal, S.; Surti, U.; Abellar, R.G.; Bateman, D.A.; Wilson, A.L.; Markham, M.H.; Slamon, J.; Santos-Simarro, F.; Palomares, M.; Nevado, J.; Lapunzina, P.; Chung, B.H.; Wong, W.L.; Chu, Y.W.; Mok, G.T.; Kerem, E.; Reiter, J.; Ambalavanan, N.; Anderson, S.A.; Kelly, D.R.; Shieh, J.; Rosenthal, T.C.; Scheible, K.; Steiner, L.; Iqbal, M.A.; McKinnon, M.L.; Hamilton, S.J.; Schlade-Bartusiak, K.; English, D.; Hendson, G.; Roeder, E.R.; DeNapoli, T.S.; Littlejohn, R.O.; Wolff, D.J.; Wagner, C.L.; Yeung, A.; Francis, D.; Fiorino, E.K.; Edelman, M.; Fox, J.; Hayes, D.A.; Janssens, S.; Baere, E. De; Menten, B.; Loccufier, A.; Vanwalleghem, L.; Moerman, P.; Sznajer, Y.; Lay, A.S.; Kussmann, J.L.; Chawla, J.; Payton, D.J.; Phillips, G.E.; Brosens, E.; Tibboel, D.; Klein, A.; Maystadt, I.; Fisher, R.; Sebire, N.; Male, A.; Chopra, M.; Pinner, J.; Malcolm, G.; Peters, G.; Arbuckle, S.; Lees, M.; Mead, Z.; Quarrell, O.; Sayers, R.; Owens, M.; Shaw-Smith, C.; Lioy, J.; McKay, E.; Leeuw, N. de; Feenstra, I.; Spruijt, L.; Elmslie, F.; Thiruchelvam, T.; Bacino, C.A.; Langston, C.; Lupski, J.R.; Sen, P.; Popek, E.; Stankiewicz, P.

    2016-01-01

    Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes

  2. Multisystem involvement of alveolar echinococcosis in a child.

    Science.gov (United States)

    Kantarci, Mecit; Bayraktutan, Ummugulsum; Pirimoglu, Berhan; Ogul, Hayri; Oral, Akgun; Eren, Suat; Gundogdu, Betul

    2014-11-13

    Alveolar echinococcosis (AE) is a chronic progressive infestation inducing a slowly progressing, life-threatening tumor-like growth in the liver. It may spread to other organs by regional extension or hematogenous or lymphatic metastasis. Herein, we report a fifteen-year-old patient diagnosed with AE of the liver and simultaneous lung and brain metastasis with a literature review.

  3. Pulmonary alveolar hemorrhage mimicking a pneumopathy: a rare ...

    African Journals Online (AJOL)

    Diffuse alveolar hemorrhage after percutaneous coronary intervention (PCI) is a rare complication. The diagnosis is difficult and can mimic by clinical and radiological features other diagnosis as pneumopathy. We herein report the case of a 63-year-old female admitted to the hospital for ST elevation myocardial infarction.

  4. Alveolar occupation infiltrations, eosinophilia in peripheral blood and bronchoalveolar lavage

    International Nuclear Information System (INIS)

    Hincapie Diaz, Gustavo Adolfo; Yama Mosquera, Erica; Guevara, Jairo

    2006-01-01

    A case of a patient of 25 years old is shown with the antecedent of no potable water consumption who entered for having pulmonary symptoms, fever, presence of alveolar occupation infiltrations and eosinophilia in peripheral blood treatment with antiparasitary started with a significant improvement of the symptoms, infiltrations and eosinophilia. It is considered eosinophilic pneumonia diagnostic by parasitary infection (Loefffers Syndrome)

  5. Alveolar occupation infiltrations, eosinophilia in peripheral blood and bronchoalveolar lavage

    International Nuclear Information System (INIS)

    Hincapie Diaz, Gustavo Adolfo; Yama Mosquera, Erica; Guevara, Jairo

    2006-01-01

    A case of a patient of 25 years old is shown with the antecedent of no potable water consumption who entered for having pulmonary symptoms. Fever, presence of alveolar occupation infiltrations and eosinophilia in peripheral blood a treatment with antiparasitary started with a significant improvement of the symptoms, infiltrations and eosinophilia. it is considered eosinophilic pneumonia diagnostic by parasitary infection (Loeffler's syndrome)

  6. Alveolar pulmonary proteinosis: case report and literature review

    International Nuclear Information System (INIS)

    Vergara, Erika; Saenz, Alberto; Ojeda, Paulina

    2009-01-01

    We describe the case of a young women with primary alveolar proteinosis, with a short period of symptoms that are uncommon for this disease, without risk factors for this entity, the clinical evolution of the patient and some complications with the treatment. We review the literature for this entity.

  7. Low Permeability Polyimide Insulation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Resodyn Technologies proposes a new technology that enables the application of polyimide based cryogenic insulation with low hydrogen permeability. This effort...

  8. Modelling of water permeability in cementitious materials

    DEFF Research Database (Denmark)

    Guang, Ye; Lura, Pietro; van Breugel, K.

    2006-01-01

    This paper presents a network model to predict the permeability of cement paste from a numerical simulation of its microstructure. Based on a linked list pore network structure, the effective hydraulic conductivity is estimated and the fluid flow is calculated according to the Hagen-Poiseuille law....... The pressure gradient at all nodes is calculated with the Gauss elimination method and the absolute permeability of the pore network is calculated directly from Darcy's law. Finally, the permeability model is validated by comparison with direct water permeability measurements. According to this model...

  9. Splenic epithelial cyst

    International Nuclear Information System (INIS)

    Yousuf, M.; Jalali, U.

    2011-01-01

    Cysts of spleen are rare entities. Congenital splenic cysts are even more uncommon comprising of only 10% of benign non-parasitic cysts. We report a case of 22 years old female who presented with history of 2 years abdominal pain and gradual distension. Ultrasound and computed tomography (CT) both were suggestive of splenic cyst. Laboratory tests show thrombocytopenia with platelets count of 97000 per cubic millimeter and anemia with hemoglobin 8.7 gram per deciliter. Serological tests were negative for parasitic infection. Splenectomy was done and the weight of the spleen was found to be 1.5 kilogram. Histopathological findings are consistent with splenic epithelial cyst. The aetiology, diagnostic modalities and treatment options are discussed in the case report. (author)

  10. Cytotoxicity and gene expression profiling of polyhexamethylene guanidine hydrochloride in human alveolar A549 cells.

    Science.gov (United States)

    Jung, Ha-Na; Zerin, Tamanna; Podder, Biswajit; Song, Ho-Yeon; Kim, Yong-Sik

    2014-06-01

    In Korea, lung disease of children and pregnant women associated with humidifier disinfectant use has become a major concern. A common sterilizer is polyhexamethylene guanidine (PHMG), a member of the guanidine family of antiseptics. This study was done to elucidate the putative cytotoxic effect of PHMG and the PHMG-mediated altered gene expression in human alveolar epithelial A549 cells in vitro. Cell viability analyses revealed the potent cytotoxicity of PHMG, with cell death evident at as low as 5 μg/mL. Death was dose- and time-dependent, and was associated with formation of intracellular reactive oxygen species, and apoptosis significantly, at even 2 μg/mL concentration. The gene expression profile in A549 cells following 24 h exposure to 5 μg/mL of PHMG was investigated using DNA microarray analysis. Changes in gene expression relevant to the progression of cell death included induction of genes related to apoptosis, autophagy, fibrosis, and cell cycle. However, the expressions of genes encoding antioxidant and detoxifying enzymes were down-regulated or not affected. The altered expression of selected genes was confirmed by quantitative reverse transcription-polymerase chain reaction and Western blot analyses. The collective data suggest that PHMG confers cellular toxicity through the generation of intracellular reactive oxygen species and alteration of gene expression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. An in vitro cytotoxicity assessment of graphene nanosheets on alveolar cells

    Science.gov (United States)

    Dervin, Saoirse; Murphy, James; Aviles, Ruth; Pillai, Suresh C.; Garvey, Mary

    2018-03-01

    The collection of intrinsic properties possessed by graphene family nanomaterials (GFNs) results in their continuous exploitation for biomedical applications. The materials biomedical potential has motivated an upsurge in green preparation routes for the production of graphene like materials with limited toxicity. A number of bio-friendly reducing agents have been utilized for the preparation of chemically reduced graphene oxide (GO), and their resulting cytotoxic effects examined. However, the toxicology effects of one of the first biomolecules implemented for the reduction of GO, ascorbic acid (AA) has yet to be investigated. Herein, the toxicity of three distinct GFNs; GO, hydrazine reduced GO (H.rGO) and AA.rGO, prepared through diverse chemical routes are studied, to demonstrate the cytotoxic activity of a green reducer, in comparison to an established reduction method using hydrazine hydrate. The variation in atomic structure of GO, H.rGO and AA.rGO resulting from different synthesis techniques demonstrates the dependence of toxicity on particle shape and size. All GFNs induced high levels of alveolar cell toxicity. Interaction of AA.rGO with the A549 human lung epithelial carcinoma cell line resulted in increased leakage of lactate dehydrogenase, indicative of diminished cell membrane integrity. The uncharacteristic shape of the AA.rGO may be responsible for this proliferated release of the essential protein. The presented data therefore demonstrates that modification of synthetic processes significantly alter the biological activities of GFNs.

  12. Receptor for advanced glycation end-products is a marker of type I lung alveolar cells.

    Science.gov (United States)

    Shirasawa, Madoka; Fujiwara, Naoyuki; Hirabayashi, Susumu; Ohno, Hideki; Iida, Junko; Makita, Koshi; Hata, Yutaka

    2004-02-01

    Lung alveolar epithelial cells are comprised of type I (ATI) and type II (ATII) cells. ATI cells are polarized, although they have very flat morphology. The identification of marker proteins for apical and basolateral membranes of ATI cells is important to investigate into the differentiation of ATI cells. In this paper, we characterized receptor for advanced glycation end-products (RAGE) as a marker for ATI cells. RAGE was localized on basolateral membranes of ATI cells in the immunoelectron microscopy and its expression was enhanced in a parallel manner to the differentiation of ATI cells in vivo and in primary cultures of ATII cells. RAGE and T1 alpha, a well-known ATI marker protein, were targeted to basolateral and apical membranes, respectively, when expressed in polarized Madine Darby canine kidney cells. Moreover, RAGE was expressed in ATI cells after T1 alpha in vivo and in ex in vivo organ cultures. In conclusion, RAGE is a marker for basolateral membranes of well-differentiated ATI cells. ATI cells require some signal provided by the in vivo environment to express RAGE.

  13. Alveolar ridge atrophy related to facial morphology in edentulous patients

    Directory of Open Access Journals (Sweden)

    Kuć J

    2017-09-01

    Full Text Available Joanna Kuć,1 Teresa Sierpińska,2 Maria Gołębiewska1 1Department of Prosthodontics, 2Department of Dental Technology, Medical University of Bialystok, Bialystok, Poland Objectives: The morphology of the alveolar process determines the retention and stability of prosthetic restorations, thereby determining the result of the therapy. Considering that the edentulous jaws may be affected by the atrophy process, it was hypothesized that the morphology of the alveolar process of the maxilla may be dependent on the anterior facial height and anatomy of the mandible. Subjects and methods: Twenty-five healthy edentulous Caucasian individuals were randomly chosen. Each subject underwent a lateral cephalogram before and after prosthetic rehabilitation. During exposition, newly made prostheses were placed in the patient’s mouth. Teeth remained in maximal intercuspidation. Morphological parameters were evaluated according to the Ricketts, McNamara, and Tallgren’s method. Results: An inversely proportional association was observed between patient age and the distal part of the maxilla. A statistically significant connection was noted between the vertical dimension of alveolar ridge and anterior total and lower facial height conditioned by prosthetic rehabilitation. Conclusion: The height of the lateral part of the alveolar ridge of the maxilla remains in connection with the anterior total and lower facial height obtained in the course of prosthetic rehabilitation. The vertical dimension of the alveolar ridge of the maxilla seems to be in close relationship with the morphology of the lower jaw. Keywords: anterior facial height, cephalometric analysis, complete dentures, vertical occlusal dimension

  14. Immunoregulation by airway epithelial cells (AECs against respiratory virus infection

    Directory of Open Access Journals (Sweden)

    Yan YAN

    2017-11-01

    Full Text Available The respiratory tract is primary contact site of the body and environment, and it is ventilated by 10-20 thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbes, which contain the disease-causing pathogens. Airway epithelial cells (AECs are known to have innate sensor functions, which are similar to the "professional" immune cells, such as alveolar macrophage and sub- or intra-epithelial dendritic cells (DCs. Thus AECs are able to detect invading microbial danger including different types of respiratory viruses, and mount a potent host response, for example, activating type Ⅰ interferon signaling pathway genes. To avoid chronic inflammation and maintain the immunological homeostasis, the pulmonary system has developed intrinsic mechanisms to control local immune responses. Most recently, the role of AECs in control of local immunity has gained much attention, as 1 AECs express the pattern recognition receptors (PRRs, such as Toll-like receptors, retinoic acid inducible gene Ⅰ (RIG-I-like receptor, and so on, thus AECs are equipped to participate in innate detection of microbial encounter; 2 To keep immunological homeostasis in the respiratory tract, AECs behave not only as innate immune sensors but also as immune modulators in parallel, through modulating the sensitivity of innate immune sensing of both AECs per se and sub- or intra-epithelial immune cells; 3 Loss of modularity capacity of AECs might be involved in the development of chronic airway diseases. In present review, how the AECs act will be intensively discussed in response to respiratory viruses and modulate the local immunity through cis- and trans-factors (direct and indirect factors, as well as the consequence of impairment of this control of local immunity, in the development and exacerbation of airway diseases, such as acute and chronic rhinosinusitis. DOI: 10.11855/j.issn.0577-7402.2017.10.02

  15. Distracción osteogénica alveolar como método de aumento del reborde alveolar

    Directory of Open Access Journals (Sweden)

    Denia Morales Navarro

    2011-03-01

    Full Text Available La distracción osteogénica alveolar, como proceso biológico de neoformación de hueso alveolar, nos motivó a la realización de la presente revisión bibliográfica, con el objetivo enfatizar en el análisis de las variables: antecedentes históricos en Cuba, clasificación de los distractores, fases de la distracción (latencia, distracción y consolidación, indicaciones, contraindicaciones, ventajas, desventajas y complicaciones. Se realizó una revisión bibliográfica mediante la consulta de bases de datos de los sistemas referativos, como MEDLINE y PubMed con la utilización de descriptores "alveolar distraction" y "osteogenic distraction". Se consultaron las fuentes bibliográficas publicadas fundamentalmente en los últimos 5 años, lo que reveló que esta técnica es una excelente alternativa para la formación de huesos y tejidos blandos en zonas de atrofia alveolar, que consta de tres etapas: latencia, distracción y consolidación; un método previsible y con bajas tasas de reabsorción ósea en comparación con otras técnicas de aumento del reborde alveolar. Tiene su principal indicación en la terapia de implantes al proveer volumen óseo. Debemos individualizar cada caso y usar el método más adecuado según las características clínicas y personales del paciente. Una adecuada selección de los casos y una mejor comprensión de la técnica son los puntales para lograr exitosos resultados mediante la distracción osteogénica alveolar. En Cuba se ha aplicado poco la distracción alveolar, por lo que ha sido necesario ampliar los estudios sobre esta temática.

  16. Three-dimensional analysis of alveolar wall destruction in the early stage of pulmonary emphysema.

    Science.gov (United States)

    Kobayashi, Yukihiro; Uehara, Takeshi; Kawasaki, Kenji; Sugano, Mitsutoshi; Matsumoto, Takehisa; Matsumoto, Gou; Honda, Takayuki

    2015-03-01

    The morphological mechanism of alveolar wall destruction during pulmonary emphysema has not been clarified. The aim of this study was to elucidate this process three-dimensionally. Lung specimens from five patients with pulmonary emphysema were used, and five controls with normal alveolar structure were also examined. Sections 150 μm thick were stained with hematoxylin and eosin, elastica, and silver impregnation, and immunostained with selected antibodies. We examined these sections three-dimensionally using a laser confocal microscope and a light microscope. There were only a few Kohn's pores and no fenestrae in the normal alveoli from the controls. In the lungs of the emphysema patients a small rupture appeared in the extremely thin alveolar wall among the alveolar capillaries. This rupture enlarged to form a circle surrounded by the capillaries, which was called an alveolar fenestra. Two neighboring fenestrae fused by breakdown of the collapsed or cord-like capillary between them to form a large fenestra. The large fenestrae fused repeatedly to become larger, and these were bordered by thick elastic fibers constructing an alveolar framework. Alveolar wall destruction during emphysema could start from small ruptures of the alveolar wall that become fenestrae surrounded by capillaries, which fuse repeatedly to become larger fenestrae rimmed with elastic fibers. The alveolar capillary network could initially prevent enlargement of the fenestrae, and the thick elastic fibers constituting the alveolar framework could secondarily prevent destruction of the alveolar wall structure. © 2014 Wiley Periodicals, Inc.

  17. Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression.

    Science.gov (United States)

    Wise, Sarah K; Laury, Adrienne M; Katz, Elizabeth H; Den Beste, Kyle A; Parkos, Charles A; Nusrat, Asma

    2014-05-01

    Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a "leaky" epithelial barrier phenotype. We hypothesize that T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 modulate epithelial junction proteins, thereby contributing to the leaky epithelial barrier. Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n = 6) and 68.6% (n = 8) of baseline, respectively. Tight junction protein junctional adhesion molecule-A (JAM-A) expression decreased 42.2% with IL-4 exposure (n = 9) and 37.5% with IL-13 exposure (n = 9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n = 9) and 32.9% with IL-13 exposure (n = 9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or zonula occludens-1 (ZO-1) with IL-4 or IL-13 exposure. Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. © 2014 ARS-AAOA, LLC.

  18. IL-4 and IL-13 Compromise the Sinonasal Epithelial Barrier and Perturb Intercellular Junction Protein Expression

    Science.gov (United States)

    Wise, Sarah K.; Laury, Adrienne M.; Katz, Elizabeth H.; Den Beste, Kyle A.; Parkos, Charles A.; Nusrat, Asma

    2014-01-01

    Introduction Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a “leaky” epithelial barrier phenotype. We hypothesize that Th2 cytokines IL-4 and IL-13 modulate epithelial junction proteins thereby contributing to the leaky epithelial barrier. Methods Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. Results IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n=6) and 68.6% (n=8) of baseline, respectively. Tight junction protein JAM-A expression decreased 42.2% with IL-4 exposure (n=9) and 37.5% with IL-13 exposure (n=9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n=9) and 32.9% with IL-13 exposure (n=9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or ZO-1 with IL-4 or IL-13 exposure. Conclusion Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. PMID:24510479

  19. Integrated Transcriptomic and Epigenomic Analysis of Primary Human Lung Epithelial Cell Differentiation

    Science.gov (United States)

    Marconett, Crystal N.; Zhou, Beiyun; Rieger, Megan E.; Selamat, Suhaida A.; Dubourd, Mickael; Fang, Xiaohui; Lynch, Sean K.; Stueve, Theresa Ryan; Siegmund, Kimberly D.; Berman, Benjamin P.

    2013-01-01

    Elucidation of the epigenetic basis for cell-type specific gene regulation is key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how epigenetic changes are integrated with transcriptional activation to determine cell phenotype during differentiation. We performed epigenomic profiling in conjunction with transcriptomic profiling using in vitro differentiation of human primary alveolar epithelial cells (AEC). This model recapitulates an in vivo process in which AEC transition from one differentiated cell type to another during regeneration following lung injury. Interrogation of histone marks over time revealed enrichment of specific transcription factor binding motifs within regions of changing chromatin structure. Cross-referencing of these motifs with pathways showing transcriptional changes revealed known regulatory pathways of distal alveolar differentiation, such as the WNT and transforming growth factor beta (TGFB) pathways, and putative novel regulators of adult AEC differentiation including hepatocyte nuclear factor 4 alpha (HNF4A), and the retinoid X receptor (RXR) signaling pathways. Inhibition of the RXR pathway confirmed its functional relevance for alveolar differentiation. Our incorporation of epigenetic data allowed specific identification of transcription factors that are potential direct upstream regulators of the differentiation process, demonstrating the power of this approach. Integration of epigenomic data with transcriptomic profiling has broad application for the identification of regulatory pathways in other models of differentiation. PMID:23818859

  20. Characteristic aspects of alveolar proteinosis diagnosis Aspectos característicos do diagnóstico da proteinose alveolar

    Directory of Open Access Journals (Sweden)

    Thiago Prudente Bártholo

    2012-02-01

    Full Text Available Alveolar proteinosis is an uncommon pulmonary disease characterized by an accumulation of surfactant in terminal airway and alveoli, thereby impairing gas exchange and engendering respiratory insufficiency in some cases. Three clinically and etiologically distinct forms of pulmonary alveolar proteinosis are recognized: congenital, secondary and idiopathic, the latter corresponding to 90% of the cases. In this case report we present a young male patient that was diagnosed with alveolar proteinosis. Computed tomography of the thorax, bronchoscopy and transbronchial biopsy were performed. The histopathologic aspect was characteristic. The patient was discharged in good health conditions and remains asymptomatic to date.Proteinose alveolar é uma doença pulmonar incomum caracterizada pelo acúmulo de surfactante nas vias aéreas terminais e nos alvéolos, alterando a troca gasosa e, em alguns casos, promovendo insuficiência respiratória. Três formas clínicas e etiologicamente distintas de proteinose alveolar são reconhecidas: congênitas, secundárias e idiopáticas (mais de 90% dos casos são de etiologia idiopática. Neste relato, apresentamos um homem jovem que foi diagnosticado com proteinose pulmonar. Tomografia computadorizada de tórax, broncoscopia e biópsia transbrônquica foram realizadas. O aspecto histopatológico foi característico. O paciente teve alta, com boas condições de saúde, e encontra-se assintomático nos dias de hoje.

  1. Crustal permeability: Introduction to the special issue

    Science.gov (United States)

    Ingebritsen, Steven E.; Gleeson, Tom

    2015-01-01

    The topic of crustal permeability is of broad interest in light of the controlling effect of permeability on diverse geologic processes and also timely in light of the practical challenges associated with emerging technologies such as hydraulic fracturing for oil and gas production (‘fracking’), enhanced geothermal systems, and geologic carbon sequestration. This special issue of Geofluids is also motivated by the historical dichotomy between the hydrogeologic concept of permeability as a static material property that exerts control on fluid flow and the perspective of economic geologists, geophysicists, and crustal petrologists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions. Issues associated with fracking, enhanced geothermal systems, and geologic carbon sequestration have already begun to promote a constructive dialog between the static and dynamic views of permeability, and here we have made a conscious effort to include both viewpoints. This special issue also focuses on the quantification of permeability, encompassing both direct measurement of permeability in the uppermost crust and inferential permeability estimates, mainly for the deeper crust.

  2. Effect of temperature on sandstone permeability

    DEFF Research Database (Denmark)

    Rosenbrand, Esther; Kjøller, Claus

    Hot water injection in geothermal sandstone aquifers is considered for seasonal energy storage in Denmark. However, an increase in the aquifer temperature might reduce permeability, and thereby increase production costs. An understanding of the factors that control permeability is required in order...... and the Klinkenberg procedure showed the expected correlation between the two measures, however, differences could be around one order of magnitude. In tight gas sandstones, permeability is often sensitive to net stress, which might change due to the pore pressure change in the Klinkenberg procedure. Besides...... affecting the Klinkenberg procedure, the combined effect of slip and changes in permeability would affect production during pressure depletion in tight gas sandstone reservoirs; therefore effects of gas slip and net stress on permeability were combined in a model based on the Klinkenberg equation. A lower...

  3. Microorganism Removal in Permeable Pavement Parking Lots ...

    Science.gov (United States)

    Three types of permeable pavements (pervious concrete, permeable interlocking concrete pavers, and porous asphalt) were monitored at the Edison Environmental Center in Edison, New Jersey for indicator organisms such as fecal coliform, enterococci, and E. coli. Results showed that porous asphalt had much lower concentration in monitored infiltrate compared to pervious concrete and permeable interlocking concrete pavers. Concentrations of monitored organisms in infiltrate from porous asphalt were consistently below the bathing water quality standard. Fecal coliform and enterococci exceeded bathing water quality standards more than 72% and 34% of the time for permeable interlocking concrete pavers and pervious concrete, respectively. Purpose is to evaluate the performance of permeable pavement in removing indicator organisms from infiltrating stormwater runoff.

  4. Oral epithelial dysplasia classification systems

    DEFF Research Database (Denmark)

    Warnakulasuriya, S; Reibel, J; Bouquot, J

    2008-01-01

    At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the United Kingdom issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers....... In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine...... use. Although most oral pathologists possibly recognize and accept the criteria for grading epithelial dysplasia, firstly based on architectural features and then of cytology, there is great variability in their interpretation of the presence, degree and significance of the individual criteria...

  5. Leukotriene B4 receptors on guinea pig alveolar eosinophils

    International Nuclear Information System (INIS)

    Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P.

    1991-01-01

    The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 x 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 ± 0.22 nM; Bmax1 = 966 ± 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 ± 8.9 nM; Bmax2 = 5557 ± 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of [3H]LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 ± 0.14 and 18.14 ± 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 x 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 x 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions

  6. Heavy metal cations permeate the TRPV6 epithelial cation channel.

    Science.gov (United States)

    Kovacs, Gergely; Danko, Tamas; Bergeron, Marc J; Balazs, Bernadett; Suzuki, Yoshiro; Zsembery, Akos; Hediger, Matthias A

    2011-01-01

    TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms.

    Science.gov (United States)

    Lechuga, Susana; Ivanov, Andrei I

    2017-07-01

    The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.

    Directory of Open Access Journals (Sweden)

    Victoria A Meliopoulos

    2016-08-01

    Full Text Available The healthy lung maintains a steady state of immune readiness to rapidly respond to injury from invaders. Integrins are important for setting the parameters of this resting state, particularly the epithelial-restricted αVβ6 integrin, which is upregulated during injury. Once expressed, αVβ6 moderates acute lung injury (ALI through as yet undefined molecular mechanisms. We show that the upregulation of β6 during influenza infection is involved in disease pathogenesis. β6-deficient mice (β6 KO have increased survival during influenza infection likely due to the limited viral spread into the alveolar spaces leading to reduced ALI. Although the β6 KO have morphologically normal lungs, they harbor constitutively activated lung CD11b+ alveolar macrophages (AM and elevated type I IFN signaling activity, which we traced to the loss of β6-activated transforming growth factor-β (TGF-β. Administration of exogenous TGF-β to β6 KO mice leads to reduced numbers of CD11b+ AMs, decreased type I IFN signaling activity and loss of the protective phenotype during influenza infection. Protection extended to other respiratory pathogens such as Sendai virus and bacterial pneumonia. Our studies demonstrate that the loss of one epithelial protein, αVβ6 integrin, can alter the lung microenvironment during both homeostasis and respiratory infection leading to reduced lung injury and improved survival.

  9. Compact rock material gas permeability properties

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huanling, E-mail: whl_hm@163.com [Key Laboratory of Coastal Disaster and Defence, Ministry of Education, Hohai University, Nanjing 210098 (China); LML, University of Lille, Cite Scientifique, 59655 Villeneuve d’Ascq (France); Xu, Weiya; Zuo, Jing [Institutes of Geotechnical Engineering, Hohai University, Nanjing 210098 (China)

    2014-09-15

    Natural compact rocks, such as sandstone, granite, and rock salt, are the main materials and geological environment for storing underground oil, gas, CO{sub 2,} shale gas, and radioactive waste because they have extremely low permeabilities and high mechanical strengths. Using the inert gas argon as the fluid medium, the stress-dependent permeability and porosity of monzonitic granite and granite gneiss from an underground oil storage depot were measured using a permeability and porosity measurement system. Based on the test results, models for describing the relationships among the permeability, porosity, and confining pressure of rock specimens were analyzed and are discussed. A power law is suggested to describe the relationship between the stress-dependent porosity and permeability; for the monzonitic granite and granite gneiss (for monzonitic granite (A-2), the initial porosity is approximately 4.05%, and the permeability is approximately 10{sup −19} m{sup 2}; for the granite gneiss (B-2), the initial porosity is approximately 7.09%, the permeability is approximately 10{sup −17} m{sup 2}; and the porosity-sensitivity exponents that link porosity and permeability are 0.98 and 3.11, respectively). Compared with moderate-porosity and high-porosity rocks, for which φ > 15%, low-porosity rock permeability has a relatively lower sensitivity to stress, but the porosity is more sensitive to stress, and different types of rocks show similar trends. From the test results, it can be inferred that the test rock specimens’ permeability evolution is related to the relative particle movements and microcrack closure.

  10. Gas and Water Permeability of Concrete

    Energy Technology Data Exchange (ETDEWEB)

    Villar, M. V.; Martin, P. L.; Romero, F. J.; Gutierrez-Rodirgo, V.; Barcala, J. M.

    2012-11-01

    The gas pressure of concrete samples was measured in an unsteady-state equipment working under low injection pressures and in a newly fine tuned steady-state setup working under different pressures. These measurements allowed the estimation of the intrinsic and relative gas permeability of the concrete and of the effect of boundary conditions on them. Permeability decreased with water content, but it was also greatly affected by the hydraulic history of concrete, i.e. if it had been previously dried or wetted. In particular, and for a given degree of saturation, the gas permeability of concrete previously saturated was lower than if the concrete had been just air dried or saturated after air drying. In any case, the gas permeability was about two orders of magnitude higher than the liquid water permeability (10-16 vs. 10-18 m2), probably due to the chemical reactions taking place during saturation (carbonation). The relative gas permeability of concrete increased sharply for water degrees of saturation smaller than 50%. The boundary conditions also affected the gas permeability, which seemed to be mostly conditioned by the back pressure and the confining pressure, increasing as the former increased and decreasing as the latter increased, i.e. decreasing as the effective pressure increased. Overall the increase of pressure head or injection pressure implied a decrease in gas permeability. External,microcracking during air-drying could not be ruled out as responsible for the decrease of permeability with confining pressure. The apparent permeability obtained applying the Klinkenberg method for a given effective pressure was only slightly smaller than the average of all the values measured for the same confining pressure range. For this reason it is considered that the Klinkenberg effect was not relevant in the range of pressures applied. (Author) 37 refs.

  11. Permeability During Magma Expansion and Compaction

    Science.gov (United States)

    Gonnermann, Helge. M.; Giachetti, Thomas; Fliedner, Céline; Nguyen, Chinh T.; Houghton, Bruce F.; Crozier, Joshua A.; Carey, Rebecca J.

    2017-12-01

    Plinian lapilli from the 1060 Common Era Glass Mountain rhyolitic eruption of Medicine Lake Volcano, California, were collected and analyzed for vesicularity and permeability. A subset of the samples were deformed at a temperature of 975°, under shear and normal stress, and postdeformation porosities and permeabilities were measured. Almost all undeformed samples fall within a narrow range of vesicularity (0.7-0.9), encompassing permeabilities between approximately 10-15 m2 and 10-10 m2. A percolation threshold of approximately 0.7 is required to fit the data by a power law, whereas a percolation threshold of approximately 0.5 is estimated by fitting connected and total vesicularity using percolation modeling. The Glass Mountain samples completely overlap with a range of explosively erupted silicic samples, and it remains unclear whether the erupting magmas became permeable at porosities of approximately 0.7 or at lower values. Sample deformation resulted in compaction and vesicle connectivity either increased or decreased. At small strains permeability of some samples increased, but at higher strains permeability decreased. Samples remain permeable down to vesicularities of less than 0.2, consistent with a potential hysteresis in permeability-porosity between expansion (vesiculation) and compaction (outgassing). We attribute this to retention of vesicle interconnectivity, albeit at reduced vesicle size, as well as bubble coalescence during shear deformation. We provide an equation that approximates the change in permeability during compaction. Based on a comparison with data from effusively erupted silicic samples, we propose that this equation can be used to model the change in permeability during compaction of effusively erupting magmas.

  12. Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion

    Science.gov (United States)

    Townley, Anna K.; Schmidt, Katy; Hodgson, Lorna; Stephens, David J.

    2012-01-01

    Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13–Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture. PMID:22331354

  13. Epithelial organization and cyst lumen expansion require efficient Sec13-Sec31-driven secretion.

    Science.gov (United States)

    Townley, Anna K; Schmidt, Katy; Hodgson, Lorna; Stephens, David J

    2012-02-01

    Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.

  14. The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis

    Science.gov (United States)

    Lesko, Alyssa C.; Goss, Kathleen H.; Yang, Frank F.; Schwertner, Adam; Hulur, Imge; Onel, Kenan; Prosperi, Jenifer R.

    2015-01-01

    The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously implicated in the control of apical-basal polarity; yet, the consequence of APC loss-of-function in epithelial polarization and morphogenesis has not been characterized. To test the hypothesis that APC is required for the establishment of normal epithelial polarity and morphogenesis programs, we generated APC-knockdown epithelial cell lines. APC depletion resulted in loss of polarity and multi-layering on permeable supports, and enlarged, filled spheroids with disrupted polarity in 3D culture. Importantly, these effects of APC knockdown were independent of Wnt/β-catenin signaling, but were rescued with either full-length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene expression signature associated with APC knockdown that points to several candidates known to regulate cell-cell and cell-matrix communication. Analysis of epithelial tissues from mice and humans carrying heterozygous APC mutations further support the importance of APC as a regulator of epithelial behavior and tissue architecture. These data also suggest that the initiation of epithelial-derived tumors as a result of APC mutation or gene silencing may be driven by loss of polarity and dysmorphogenesis. PMID:25578398

  15. Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

    International Nuclear Information System (INIS)

    Dairou, Julien; Petit, Emile; Ragunathan, Nilusha; Baeza-Squiban, Armelle; Marano, Francelyne; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2009-01-01

    Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and β-naphthylamine (β-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H 2 O 2 or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.

  16. Suitability of Torrent Permeability Tester to measure air-permeability of covercrete

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, C.; Gonzales-Gasca, C. [Institute of Construction Sciences ' Eduardo Torroja' , Madrid (Spain); Torrent, R. [Portland Cement Institute, (Argentina)

    2000-07-01

    Suitability of the Torrent Permeability Tester (TPT) to measure the permeability of covercrete to air, both in the laboratory and the field, is investigated, and test results obtained in laboratory studies are discussed. The tests performed included the determination of air permeability (TPT method), oxygen permeability (Cembureau method) and capillary suction, rapid chloride permeability test (ASTM C 1202), as well as a one-year carbonation depth test. Concrete specimens of various compositions and curing regimes were used in the tests; the gas-permeability tests were repeated on the same specimens after 28 days, than again at 6 months and 12 months. Test results confirmed the suitability of the TPT as a useful tool in the characterization of the quality the of concrete cover. It was found to be sensitive to changes in concrete quality; repeatable for sensitive properties such as gas permeability ; also, it was found to correlate well with other durability-related properties. 10 refs., 8 tabs., 8 figs.

  17. Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

    Science.gov (United States)

    Rotoli, Bianca Maria; Bussolati, Ovidio; Costa, Anna Luisa; Blosi, Magda; Di Cristo, Luisana; Zanello, Pier Paolo; Bianchi, Massimiliano G.; Visigalli, Rossana; Bergamaschi, Enrico

    2012-09-01

    Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO2 NPs (size range 4-33 nm), two preparations of CeO2 NPs (9-36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15-240 μg/cm2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm2, in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO2 and CeO2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured nanomaterials.

  18. Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

    International Nuclear Information System (INIS)

    Rotoli, Bianca Maria; Bussolati, Ovidio; Costa, Anna Luisa; Blosi, Magda; Di Cristo, Luisana; Zanello, Pier Paolo; Bianchi, Massimiliano G.; Visigalli, Rossana; Bergamaschi, Enrico

    2012-01-01

    Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO 2 NPs (size range 4–33 nm), two preparations of CeO 2 NPs (9–36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15–240 μg/cm 2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm 2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm 2 , in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO 2 and CeO 2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured

  19. Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

    Science.gov (United States)

    Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

    2017-01-01

    Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

  20. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    2010-03-01

    Full Text Available Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  1. MRI and CT in alveolar echinococcosis of the liver

    International Nuclear Information System (INIS)

    Duewell, S.; Marincek, B.; Schulthess, G.K. von; Ammann, R.; Zurich Univ.

    1990-01-01

    To compare the value of MRI and CT in evaluating hepatic alveolar echinococcosis a study was conducted on 30 patients. The liver was initially affected in all patients. At the time of examination, 15 patients had undergone partial liver resection. MRI showed no advantage over CT in demonstrating an echinococcal mass lesion. MRI was superior in identifying concomitant pathological changes of the intrahepatic and extrahepatic venous system due to the intrinsic contrast of vascular structures. However, CT was superior in identifying calcifications, an important attribute of the disease. MRI should only be used in imaging alveolar echinococcosis of the liver if diagnostic questions remain open after CT, in particular questions concerning venous pathology. MRI may also be used to replace CT in patients with a contraindication to urographic contrast material. (orig.) [de

  2. CT findings of extrahepatic alveolar echinococcus (report of 12 cases)

    International Nuclear Information System (INIS)

    Liu Wenya; Shang Ge; Dang Jun

    2000-01-01

    Objective: To analyze the CT findings of extrahepatic alveolar echinococcus (EAE), and assess the value of CT scanning for the diagnosis of such cases. Methods: 12 patients with hepatic alveolar echinococcus (HAE) verified by operation and histology were examined by CT because of new complains. It was found that multiple organs were involved by the same lesions. Results: Brain AE (7 cases) showed single or multiple cerebral nodules, characterized by honeycombed hypodense structures or target sign after enhancement. Lung AE (3 cases) appeared as irregular, peripherally scattered nodules, with small vacuoles or cavities inside. The only 1 case with heart AE demonstrated a multiple calcifications and vacuoles within the mass. Adrenal gland AE (2 cases) presented as plaques containing different sizes of hypodense areas and calcifications. Retroperitoneal AE (2 cases) exhibited mass with plentiful calcifications. Conclusion: CT can define the location and morphology of the lesion, providing a reliable method for the diagnosis and treatment of the disease

  3. Imaging diagnosis of alveolar echinococcosis in young patients

    International Nuclear Information System (INIS)

    Sasaki, F.; Ohkawa, Y.; Sato, N.; Uchino, J.; Hata, Y.

    1997-01-01

    We review the imaging findings in seven children with alveolar echinococcosis of the liver. Calcification was seen on plain abdominal films in five of seven patients (66.6 %); the calcifications were small or coarse with irregular margins. Ultrasound was performed in four cases, identifying the lesions in all four as small calcifications with or without cysts. Computed tomography (CT) was performed in four cases and showed small calcifications, calcifications surrounding a cyst, or an aggregate of calcifications. Angiography was performed in all seven patients and showed changes of intrahepatic arterial stretching, overgrowth of small arteries, and a honeycomb pattern in the capillary phase. Venography revealed compression of the inferior vena cava in two patients. Serum screening together with ultrasonography and CT are useful for diagnostic imaging of alveolar echinococcosis. (orig.). With 3 figs., 2 tabs

  4. Proximal alveolar bone loss in a longitudinal radiographic investigation

    International Nuclear Information System (INIS)

    Lavstvedt, S.; Bolin, A.; Henrikson, C.O.; Carstensen, J.

    1986-01-01

    A longitudinal radiographic investigation was made of the progression of the proximal alveolar bone loss over a 10-year period (1970-1980). The material was unselected and consisted of 669 individuals in the county of Stockholm. 61 individuals were randomly selected for evaluation of a recording system using alternative methods of measurement, and 90% of the measurement sites could then be assessed. The correlations between some of the methods were high, such as between measurement of alveolar bone height and root length and between aleveolar bone height and tooth length. To reduce the number of measurements, a partial recording was made, giving a high correlation coefficient between the partial recording and total recording. When five measurement sites were used, the correlation coefficient was 0.96, and a slight increase of the coefficient was obtained when using additional sites

  5. Arched needle technique for inferior alveolar mandibular nerve block.

    Science.gov (United States)

    Chakranarayan, Ashish; Mukherjee, B

    2013-03-01

    One of the most commonly used local anesthetic techniques in dentistry is the Fischer's technique for the inferior alveolar nerve block. Incidentally this technique also suffers the maximum failure rate of approximately 35-45%. We studied a method of inferior alveolar nerve block by injecting a local anesthetic solution into the pterygomandibular space by arching and changing the approach angle of the conventional technique and estimated its efficacy. The needle after the initial insertion is arched and inserted in a manner that it approaches the medial surface of the ramus at an angle almost perpendicular to it. The technique was applied to 100 patients for mandibular molar extraction and the anesthetic effects were assessed. A success rate of 98% was obtained.

  6. Alveolar echinococcosis of the liver - computed tomographic findings

    International Nuclear Information System (INIS)

    Merkle, E.; Usadel, S.; Vogel, J.; Kern, P.; Friedrich, J.M.; Brambs, H.J.

    1995-01-01

    In order to ascertain the typical computed tomographic findings of hepatic alveolar echinococcosis, 24 computed tomograms of 19 patients were evaluated. The liver was involved in all cases whereas the diaphragma was infiltrated in 32%, and the retroperioteneal area in 42%. The right liver lobe was affected in 65%. Both before and after intravenous bolus contrast medium administration, the lesions were mainly inhomogeneous and of low density; a masking of the lesions due to the contrast medium administration was not observed; the enhancement pattern was irregular. Calcifications were detected in 96% of the cases, cystic structures in 50%, and cholestasis in 54%. On the basis of the crucial finding of calcifications in combination with the other typical observations, CT seems to be very suitable for the evaluation of hepatic alveolar echinococcosis. (orig.) [de

  7. A plate reader-based method for cell water permeability measurement

    DEFF Research Database (Denmark)

    Fenton, Robert A.; Moeller, H B; Nielsen, S

    2010-01-01

    Cell volume and water permeability measurements in cultured mammalian cells are typically conducted under a light microscope. Many of the employed approaches are time consuming and not applicable to a study of confluent epithelial cell monolayers. We present here an adaptation of a calcein......: AQP2-S256D > AQP2 wild-type > AQP2-S256A. We propose that the method can be applied to study AQP function and more generally to study cell volume changes in adherent cell lines. Furthermore, it should be adaptable for AQP inhibitor screening in chemical compound libraries....

  8. Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

    Directory of Open Access Journals (Sweden)

    Gintaras Juodzbalys

    2011-01-01

    Full Text Available Objectives: The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement.Material and Methods: Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies.Results: In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement.Conclusions: The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management.

  9. Effect of ozone and histamine on airway permeability to horseradish peroxidase in guinea pigs

    International Nuclear Information System (INIS)

    Miller, P.D.; Gordon, T.; Warnick, M.; Amdur, M.O.

    1986-01-01

    Airway permeability was studied in groups of male guinea pigs at 2, 8, and 24 h after a 1-h exposure to 1 ppm ozone or at 2 h after a 1-h exposure to filtered air (control). Intratracheal administration of 2 mg horseradish peroxidase (HRP) was followed by blood sampling at 5-min intervals up to 30 min. The rate of appearance of HRP in plasma was significantly higher at 2 and 8 h after ozone exposure than that found in animals examined 2 h after air exposure or 24 h after ozone exposure. A dose of 0.12 mg/kg of subcutaneous histamine given after the 15 min blood sample significantly increased the already elevated permeability seen at 2 h post ozone, but had no effect on animals exposed to filtered air 2 h earlier or to ozone 24 h earlier. No difference was seen in the amount of subcutaneous radiolabeled histamine in the lungs of animals exposed 2 h earlier either to air or to ozone. These data indicate that a short-term exposure to ozone produced a reversible increase in respiratory epithelial permeability to HRP in guinea pigs. The potentiation of this increased permeability by histamine may be another manifestation of ozone-induced hyperreactivity

  10. Water permeability of acinar cell membranes in the isolated perfused rabbit mandibular salivary gland.

    Science.gov (United States)

    Steward, M C; Seo, Y; Rawlings, J M; Case, R M

    1990-01-01

    1. The diffusive water permeability of epithelial cell membranes in the perfused rabbit mandibular salivary gland was measured at 37 degrees C by a 1H nuclear magnetic resonance relaxation method using an extracellular relaxation reagent, gadolinium diethylenetriaminepentaacetic acid (Gd(DTPA)). 2. In glands perfused with a HEPES-buffered solution containing 10 mmol l-1 Gd(DTPA), the spin-lattice (T1) relaxation of the water protons showed two exponential components. The water compartment responsible for the slower component corresponded in magnitude to 71 +/- 5% of the wet weight of the gland, and was attributed to the exchangeable intracellular water of the acinar cells. 3. The rate constant for water efflux from the cells was estimated to be 4.1 +/- 0.1 s-1 which would be consistent with a diffusive membrane permeability (Pd) of approximately 3 x 10(-3) cm s-1. Stimulation with acetylcholine (10(-6) mol l-1) did not cause any detectable change in membrane water permeability. 4. Since the basolateral membrane probably provides the main pathway for water efflux, the osmotic water permeability of this barrier (expressed per gland) was estimated to be less than 6.2 cm3 s-1. This would be insufficient to account for the generation of a near-isosmotic fluid at the flow rates observed during secretion, and suggests that a substantial fraction of the flow of water occurs via a paracellular route. PMID:1966053

  11. Primary Pulmonary Plasmacytoma with Diffuse Alveolar Consolidation: A Case Report

    Directory of Open Access Journals (Sweden)

    Zohreh Mohammad Taheri

    2010-01-01

    Full Text Available Solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the sinonasal or nasopharyngeal regions. Primary plasmacytoma of the lung is exceedingly rare and often presents as a solitary mass or nodule in mid-lung or hilar areas and diagnosed after resection. Herein, we report a case of primary pulmonary plasmacytoma that presented with diffuse alveolar consolidation and diagnosed by transbronchial lung biopsy.

  12. Role of Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Vlahos, Ross; Bozinovski, Steven

    2014-01-01

    Alveolar macrophages (AMs) represent a unique leukocyte population that responds to airborne irritants and microbes. This distinct microenvironment coordinates the maturation of long-lived AMs, which originate from fetal blood monocytes and self-renew through mechanisms dependent on GM-CSF and CSF-1 signaling. Peripheral blood monocytes can also replenish lung macrophages; however, this appears to occur in a stimuli specific manner. In addition to mounting an appropriate immune response durin...

  13. Correlation between alveolar ventilation and electrical properties of lung parenchyma

    OpenAIRE

    Roth, J. C., Ehrl, A., Becher, T., Frerichs, I., Schittny, J., Weller, N., Wall W. A.

    2016-01-01

    One key problem in modern medical imaging is linking measured data and actual physiological quantities. In this article we derive such a link between the electrical bioimpedance of lung parenchyma, which can be measured by electrical impedance tomography (EIT), and the magnitude of regional ventilation, a key towards understanding lung mechanics and developing novel protective ventilation strategies. Two rat-derived three-dimensional alveolar microstructures obtained from synchrotron-ba...

  14. Coronectomy - A viable alternative to prevent inferior alveolar nerve injury

    Directory of Open Access Journals (Sweden)

    Alok Sagtani

    2015-12-01

    Full Text Available Background and Objectives: Coronectomy is a relatively new method to prevent the risk of Inferior Alveolar Nerve (IAN injury during removal of lower third molars with limited scientific literature among Nepalese patients. Thus, a study was designed to evaluate coronectomy regarding its use, outcomes and complications.Materials and Methods: A descriptive study was conducted from December 2012 to December 2013 among patients attending Department of Oral and Maxillofacial Surgery, College of Dental Sciences, BP Koirala Institute of Health Sciences, Dharan, Nepal for removal of mandibular third molars. After reviewing the radiograph for proximity of third molar to the IAN, coronectomy was advised. A written informed consent was obtained from the patients and coronectomy was performed. Patients were recalled after one week. The outcome measures in the follow-up visit were primary healing, pain, infection, dry socket, root exposure and IAN injury. The prevalence of IAN proximity of lower third molars and incidence of complications were calculated.Results: A total 300 mandibular third molars were extracted in 278 patients during the study period. Out of 300 impacted mandibular third molar, 41 (13.7% showed close proximity to inferior alveolar nerve . The incidence of complications and failed procedure was 7.4% among the patients who underwent coronectomy. During the follow up visit, persistent pain and root exposure was reported while other complications like inferior alveolar nerve injury, dry socket and infection was not experienced by the study patients.Conclusion: With a success rate of 92.6% among the 41 patients, coronectomy is a viable alternative to conventional total extraction for mandibular third molars who have a higher risk for damage to the inferior alveolar nerve.JCMS Nepal. 2015;11(3:1-5.

  15. Alveolar cell carcinoma: diagnostic pitfalls in evaluating the chest roentgenogram

    International Nuclear Information System (INIS)

    Shin, M.S.; Bailey, W.C.

    1985-01-01

    A report is given of two patients with initial symptoms of congestive heart failure who had an extensive work-up that failed to reveal any signs of pulmonary malignancy. Subsequent biopsy by fiberoptic bronchoscopy confirmed alveolar cell carcinoma in both cases, suggesting that bronchoscopy with biopsy should be considered in patients with congestive heart failure if pulmonary edema does not resolve with appropriate therapy. 11 references, 2 figures

  16. Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis

    OpenAIRE

    Goroshi, Manjunath; Lila, Anurag R.; Bandgar, Tushar; Shah, Nalini S.

    2018-01-01

    Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhanceme...

  17. An unclassified Eubacterium taxon in acute dento-alveolar abscess.

    Science.gov (United States)

    Wade, W G; Lewis, M A; Cheeseman, S L; Absi, E G; Bishop, P A

    1994-02-01

    The microflora of pus samples aspirated from 50 acute dento-alveolar abscesses was examined. A total of 143 bacterial strains was isolated, consisting predominantly of Prevotella spp., alpha-haemolytic Streptococcus spp., Peptostreptococcus spp. and Eubacterium spp. An unclassified asaccharolytic Eubacterium taxon was encountered in 17 (34%) of the abscesses. This taxon was found to have a positive association with Fusobacterium spp. and a negative association with alpha-haemolytic Streptococcus spp.

  18. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse

    Science.gov (United States)

    Arrieta, M C; Madsen, K; Doyle, J; Meddings, J

    2008-01-01

    Background: Defects in the small intestinal epithelial barrier have been associated with inflammatory bowel disease but their role in the causation of disease is still a matter of debate. In some models of disease increased permeability appears to be a very early event. The interleukin 10 (IL10) gene-deficient mouse spontaneously develops colitis after 12 weeks of age. These mice have been shown to have increased small intestinal permeability that appears early in life. Furthermore, the development of colitis is dependent upon luminal agents, as animals do not develop disease if raised under germ-free conditions. Aims: To determine if the elevated small bowel permeability can be prevented, and if by doing so colonic disease is prevented or attenuated. Methods: IL10 gene-deficient (IL10−/−) mice) were treated with AT-1001 (a zonulin peptide inhibitor), a small peptide previously demonstrated to reduce small intestinal permeability. Small intestinal permeability was measured, in vivo, weekly from 4 to 17 weeks of age. Colonic disease was assessed at 8 weeks in Ussing chambers, and at 17 weeks of age inflammatory cytokines and myeloperoxidase were measured in the colon. Colonic permeability and histology were also endpoints. Results: Treated animals showed a marked reduction in small intestinal permeability. Average area under the lactulose/mannitol time curve: 5.36 (SE 0.08) in controls vs 3.97 (SE 0.07) in the high-dose AT-1001 group, p<0.05. At 8 weeks of age there was a significant reduction of colonic mucosal permeability and increased electrical resistance. By 17 weeks of age, secretion of tumour necrosis factor α (TNFα) from a colonic explant was significantly lower in the treated group (25.33 (SE 4.30) pg/mg vs 106.93 (SE 17.51) pg/ml in controls, p<0.01). All other markers also demonstrated a clear reduction of colitis in the treated animals. Additional experiments were performed which demonstrated that AT-1001 was functionally active only in the small

  19. Permeability Barrier Generation in the Martian Lithosphere

    Science.gov (United States)

    Schools, Joe; Montési, Laurent

    2015-11-01

    Permeability barriers develop when a magma produced in the interior of a planet rises into the cooler lithosphere and crystallizes more rapidly than the lithosphere can deform (Sparks and Parmentier, 1991). Crystallization products may then clog the porous network in which melt is propagating, reducing the permeability to almost zero, i.e., forming a permeability barrier. Subsequent melts cannot cross the barrier. Permeability barriers have been useful to explain variations in crustal thickness at mid-ocean ridges on Earth (Magde et al., 1997; Hebert and Montési, 2011; Montési et al., 2011). We explore here under what conditions permeability barriers may form on Mars.We use the MELTS thermodynamic calculator (Ghiorso and Sack, 1995; Ghiorso et al., 2002; Asimow et al., 2004) in conjunction with estimated Martian mantle compositions (Morgan and Anders, 1979; Wänke and Dreibus, 1994; Lodders and Fegley, 1997; Sanloup et al., 1999; Taylor 2013) to model the formation of permeability barriers in the lithosphere of Mars. In order to represent potential past and present conditions of Mars, we vary the lithospheric thickness, mantle potential temperature (heat flux), oxygen fugacity, and water content.Our results show that permeability layers can develop in the thermal boundary layer of the simulated Martian lithosphere if the mantle potential temperature is higher than ~1500°C. The various Martian mantle compositions yield barriers in the same locations, under matching variable conditions. There is no significant difference in barrier location over the range of accepted Martian oxygen fugacity values. Water content is the most significant influence on barrier development as it reduces the temperature of crystallization, allowing melt to rise further into the lithosphere. Our lower temperature and thicker lithosphere model runs, which are likely the most similar to modern Mars, show no permeability barrier generation. Losing the possibility of having a permeability

  20. Alveolar echinococcosis of the liver. Findings of magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hayasaka, Kazumasa; Tanaka, Yoshiaki; Okuhata, Yoshitaka; Yoshinobu, Takashi; Takemoto, Akiko; Himi, Kazuhisa; Mutoh, Haruomi [Nihon Univ., Tokyo (Japan). School of Medicine; Shuke, Noriyuki; Aburano, Tamio

    1995-06-01

    The purpose of the present study was to evaluate the findings of MR imaging obtained in patients with Echinococcus multilocularis involving the liver. For 10 patients with alveolar echinococcosis of the liver, the MR findings were compared with the histopathologic findings after biopsy or surgery. Conventional T1-weighted spin echo, T2-weighted spin echo and T1-weighted spin echo after Gd-DTPA were employed. The signal from the lesions of alveolar liver echinococcosis on T1-weighted images was hypointense in 16 of 23 lesions (69.6%), hyperintense in 4 (17.4%), and isointense in 3 (13.0%). The signal from the lesions on T2-weighted images was hyperintense in 20 lesions (87.0%), hypointense in 2 (8.7%), and isointense in one (4.3%). On using Gd-DTPA, 7 of 21 lesions (33.3%) were observed with rim enhancement, and 14 lesions (66.7%) were non-enhanced. We describe our clinical experience together with the various findings of MR imaging as observed in the patients with alveolar echinococcosis of the liver. MR imaging excels in visualizing a low-intensity rim and small cystic foci, with liquefaction necrotic foci displaying a variety of signal intensities. After Gd-DTPA administration, the surrounding inflammatory granulomatous foci could be more clearly visualized. (author).

  1. Alveolar echinococcosis of the liver. Findings of magnetic resonance imaging

    International Nuclear Information System (INIS)

    Hayasaka, Kazumasa; Tanaka, Yoshiaki; Okuhata, Yoshitaka; Yoshinobu, Takashi; Takemoto, Akiko; Himi, Kazuhisa; Mutoh, Haruomi; Shuke, Noriyuki; Aburano, Tamio.

    1995-01-01

    The purpose of the present study was to evaluate the findings of MR imaging obtained in patients with Echinococcus multilocularis involving the liver. For 10 patients with alveolar echinococcosis of the liver, the MR findings were compared with the histopathologic findings after biopsy or surgery. Conventional T1-weighted spin echo, T2-weighted spin echo and T1-weighted spin echo after Gd-DTPA were employed. The signal from the lesions of alveolar liver echinococcosis on T1-weighted images was hypointense in 16 of 23 lesions (69.6%), hyperintense in 4 (17.4%), and isointense in 3 (13.0%). The signal from the lesions on T2-weighted images was hyperintense in 20 lesions (87.0%), hypointense in 2 (8.7%), and isointense in one (4.3%). On using Gd-DTPA, 7 of 21 lesions (33.3%) were observed with rim enhancement, and 14 lesions (66.7%) were non-enhanced. We describe our clinical experience together with the various findings of MR imaging as observed in the patients with alveolar echinococcosis of the liver. MR imaging excels in visualizing a low-intensity rim and small cystic foci, with liquefaction necrotic foci displaying a variety of signal intensities. After Gd-DTPA administration, the surrounding inflammatory granulomatous foci could be more clearly visualized. (author)

  2. Massive Alveolar Hemorrhage During Wegener Granulomatosis: a Case Report

    Directory of Open Access Journals (Sweden)

    Gökhan Perincek

    2011-11-01

    Full Text Available This is a presentation of Wegener Granulomatosis (WG disease. Even though the lungs are rarely affected. massive alveolar hemorrhage is seen which leads to mortality. The patient was a 28 year old man. His illness was diagnosed as WG and glomerulonephritis a year previously and he was treated by administration of methylprednisolone orally. He had been treated irregularly. He applied to the emergency service with hemoptysis and asthma complaints two days earlier. After the results of his examination Hb: 3.6 gr/dl, Htc:10.3%, Üre:131 mg /dl, kreatini: 7.7 mg/dl, pH: 7.41, pO2: 55 mmHg, pCO2:33 mmHg, and being diagnosed as alveolar consolidation on lung X-ray, he was taken to the intensive care unit with a diagnosis of a massive alveolar hemorrhagei. He was intubated and attached to mechanical ventilation. He was treated with parenteral 1 mg/kg/day methylprednisolone and, siklofosfamid 2 mg/kg/day. He was extubated on the 21st day. He was taken to the chest service department on 24th day. He is still being treated.

  3. Requirement of alveolar bone formation for eruption of rat molars

    Science.gov (United States)

    Wise, Gary E.; He, Hongzhi; Gutierrez, Dina L.; Ring, Sherry; Yao, Shaomian

    2011-01-01

    Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (BMP6), was inhibited by injection of the 1st mandibular molar of the rat with an siRNA targeted against BMP6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption either was delayed or completely inhibited (7 molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced as compared to the erupted first molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that BMP6 may be an essential gene for promoting this growth. PMID:21896048

  4. Alveolar ridge keratosis--a retrospective clinicopathological study.

    Science.gov (United States)

    Bellato, Lorenzo; Martinelli-Kläy, Carla P; Martinelli, Celso R; Lombardi, Tommaso

    2013-04-16

    Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK. The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient's gender, age, anatomical location, tobacco and alcohol use were analyzed. Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia. Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK.

  5. Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

    Directory of Open Access Journals (Sweden)

    Xinxin Liu

    Full Text Available Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3 expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001. Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (p<0.05 and a reduction in transepithelial electrical resistance (TEER by 180.0% (p<0.001. While the expression of tight junctional protein did not change in acrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (p<0.05. Taken together, these data provide evidence that acute acrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium.

  6. Permeability Tests on Silkeborg Sand No. 0000

    DEFF Research Database (Denmark)

    Lund, Willy; Jakobsen, Kim Parsberg

    on the characteristics of the soil matrix, the permeability is determined for different void ratios. All tests are performed on reconstituted specimens of Silkeborg Sand No. 0000. The permeability is determined by use of a falling head apparatus. The apparatus, test procedures and the analysis method are described......The flow through porous media plays an important role in various engineering disciplines, as for example in ground water hydrology and soil mechanics. In the present study the permeability is determined for a fine, saturated sand. As the flow through a porous media strongly depends...

  7. Permeability Tests on Eastern Scheldt Sand

    DEFF Research Database (Denmark)

    Jakobsen, Kim Parsberg

    on the characteristics of the soil matrix, the permeability is determined for different void ratios. All tests are performed on reconstituted specimens of Eastern Scheldt Sand. The permeability is determined by use of a falling head apparatus. Finally the test results are briefly summarised and a relationship between......The flow through porous media plays an important role in various engineering disciplines, as for example in ground water hydrology and soil mechanics. In the present study the permeability is determined for a fine, saturated sand. As the flow through a porous media strongly depends...

  8. Oral epithelial cell reaction after exposure to Invisalign plastic material.

    Science.gov (United States)

    Premaraj, Thyagaseely; Simet, Samantha; Beatty, Mark; Premaraj, Sundaralingam

    2014-01-01

    Invisalign plastic aligners (Align Technology, Santa Clara, Calif) are used to correct malocclusions. The aligners wrap around the teeth and are in contact with gingival epithelium during treatment. The purpose of this study was to evaluate the cellular responses of oral epithelium exposed to Invisalign plastic in vitro. Oral epithelial cells were exposed to eluate obtained by soaking Invisalign plastic in either saline solution or artificial saliva for 2, 4, and 8 weeks. Cells grown in media containing saline solution or saliva served as controls. Morphologic changes were assessed by light microscopy. The 3-[4, 5-dimethythiazol- 2-yl]-2, 5-diphenyl tetrazolium bromide assay and flow cytometry were used to determine cell viability and membrane integrity, respectively. Cellular adhesion and micromotion of epithelial cells were measured in real time by electrical cell-substrate impedance sensing. Cells exposed to saline-solution eluate appeared rounded, were lifted from the culture plates, and demonstrated significantly increased metabolic inactivity or cell death (P <0.05). Saliva eluates did not induce significant changes in cell viability compared with untreated cells. Flow cytometry and electric cell-substrate impedance sensing showed that cells treated with saline-solution eluate exhibited compromised membrane integrity, and reduced cell-to-cell contact and mobility when compared with saliva-eluate treatment. Exposure to Invisalign plastic caused changes in viability, membrane permeability, and adhesion of epithelial cells in a saline-solution environment. Microleakage and hapten formation secondary to compromised epithelial integrity might lead to isocyanate allergy, which could be systemic or localized to gingiva. However, these results suggest that saliva might offer protection. Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  9. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.

    Science.gov (United States)

    Drago, Sandro; El Asmar, Ramzi; Di Pierro, Mariarosaria; Grazia Clemente, Maria; Tripathi, Amit; Sapone, Anna; Thakar, Manjusha; Iacono, Giuseppe; Carroccio, Antonio; D'Agate, Cinzia; Not, Tarcisio; Zampini, Lucia; Catassi, Carlo; Fasano, Alessio

    2006-04-01

    Little is known about the interaction of gliadin with intestinal epithelial cells and the mechanism(s) through which gliadin crosses the intestinal epithelial barrier. We investigated whether gliadin has any immediate effect on zonulin release and signaling. Both ex vivo human small intestines and intestinal cell monolayers were exposed to gliadin, and zonulin release and changes in paracellular permeability were monitored in the presence and absence of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement, and zonula occludens-1 (ZO-1) redistribution were evaluated by immunofluorescence microscopy. Tight junction occludin and ZO-1 gene expression was evaluated by real-time polymerase chain reaction (PCR). When exposed to gliadin, zonulin receptor-positive IEC6 and Caco2 cells released zonulin in the cell medium with subsequent zonulin binding to the cell surface, rearrangement of the cell cytoskeleton, loss of occludin-ZO1 protein-protein interaction, and increased monolayer permeability. Pretreatment with the zonulin antagonist FZI/0 blocked these changes without affecting zonulin release. When exposed to luminal gliadin, intestinal biopsies from celiac patients in remission expressed a sustained luminal zonulin release and increase in intestinal permeability that was blocked by FZI/0 pretreatment. Conversely, biopsies from non-celiac patients demonstrated a limited, transient zonulin release which was paralleled by an increase in intestinal permeability that never reached the level of permeability seen in celiac disease (CD) tissues. Chronic gliadin exposure caused down-regulation of both ZO-1 and occludin gene expression. Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.

  10. Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis

    International Nuclear Information System (INIS)

    Miller, M.J.; Adams, J.; Gu, X.A.; Zhang, X.J.; Clark, D.A.

    1990-01-01

    We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of [51Cr]EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loops receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in [51Cr]EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress

  11. Asbestosis. Bronchoalveolar lavage fluid proteins and their relationship to pulmonary epithelial permeability

    International Nuclear Information System (INIS)

    Gellert, A.R.; Perry, D.; Langford, J.A.; Riches, P.G.; Rudd, R.M.

    1985-01-01

    The authors measured levels of albumin and immunoglobulins in serum and bronchoalveolar lavage (BAL) fluid in 28 men with asbestosis and 11 control subjects. The half-time clearance of inhaled diethylene triamine pentacetate labelled with technetium-99m (/sup 99m/Tc-DTPA) from the lungs (t1/2LB) was measured in 26 patients with asbestosis and in 31 normal nonsmoking controls. In those individuals in whom immunoglobulins were detected in BAL fluid, the mean IgG:albumin ratio in BAL fluid was 0.30, significantly less than the ratio of 0.43 in control subjects. There was no significant difference in IgA:albumin ratios between patients and control subjects. The mean BAL:serum albumin ratio in patients with asbestosis was 2.3 X 10(-3). The t1/2LB was significantly shorter in both smokers and nonsmokers with asbestosis, compared with 31 normal nonsmoking controls, but there were no relationships between t1/2LB and BAL:serum albumin ratio or any other BAL protein levels in either smokers or nonsmokers with asbestosis

  12. Measurement of pulmonary epithelial permeability with /sup 99m/Tc-DTPA aerosol

    International Nuclear Information System (INIS)

    Coates, G.; O'Brodovich, H.

    1986-01-01

    The rate at which inhaled aerosol of /sup 99m/Tc-diethylenetriamine pentaacetate (DTPA) leaves the lung by diffusion into the vascular space can be measured with a gamma camera or simple probe. In normal humans, /sup 99m/Tc-DTPA clears from the lung with a half time of about 80 minutes. Many acute and chronic conditions that alter the integrity of the pulmonary epithelium cause an increased clearance rate. Thus cigarette smoking, alveolitis from a variety of causes, adult respiratory distress syndrome (ARDS), and hyaline membrane disease (HMD) in the infant have all been shown to be associated with rapid pulmonary clearance of /sup 99m/Tc-DTPA. Rapid clearance is also promoted by increased lung volume and decreased surfactant activity. Although the mechanism of increased clearance in pathological states is not known, the /sup 99m/Tc-DTPA lung-clearance technique has great potential clinically, particularly in patients at risk from ARDS and HMD and in the diagnosis and follow-up of alveolitis. 58 references

  13. Treatment of sharp mandibular alveolar process with hybrid prosthesis

    Directory of Open Access Journals (Sweden)

    Sukaedi Sukaedi

    2010-09-01

    Full Text Available Background: Losing posterior teeth for a long time would occasionally lead to the sharpening of alveolar process. The removable partial denture usually have problems when used during mastication, because of the pressure on the mucosa under the alveolar ridge. Purpose: The purpose of this case report was to manage patients with sharp mandibular alveolar process by wearing hybrid prosthesis with extra coronal precision attachment retention and soft liner on the surface base beneath the removable partial denture. Case: A 76 years old woman visited the Prosthodontic Clinic Faculty of Dentistry Airlangga University. The patient had a long span bridge on the upper jaw and a free end acrylic removable partial denture on the lower jaw. She was having problems with mastication. The patient did not wear her lower denture because of the discomfort with it during mastication. Hence, she would like to replace it with a new removable partial denture. Case management: The patient was treated by wearing a hybrid prosthesis with extra coronal precision attachment on the lower jaw. Soft liner was applied on the surface of the removable partial denture. Hybrid prosthesis is a complex denture consisting of removable partial denture and fixed bridge. Conclusion: It concluded that after restoration, the patient had no problems with sharp alveolar process with her new denture, and she was able to masticate well.Latar belakang: Kehilangan geligi posterior dapat menimbulkan processus alveolaris tajam. Gigi tiruan sebagian lepasan mempunyai masalah selama pengunyahan karena adanya tekanan di mukosa di bawah alveolar ridge. Tujuan: Tujuan laporan kasus ini adalah untuk menjelaskan cara menangani pasien yang mempunyai prosesus alveolaris yang tajam di rahang bawah dengan dibuatkan protesis hybrid dengan daya tahan extra coronal precision attachment dan soft liner di permukaan bawah basis gigi tiruan sebagian lepasan. Kasus: Pasien wanita berumur 76 tahun datang di klinik

  14. Borehole stoneley waves and permeability: Laboratory results

    International Nuclear Information System (INIS)

    Winkler, K.W.; Plona, T.J.; Froelich, B.; Liu, H.L.

    1987-01-01

    Recent interest in full waveform sonic logging has created the need for full waveform laboratory experiments on model boreholes. Of particular interest is the investigation of Stoneley waves and their interaction with permeable formations. The authors describe experimental results that show how Stoneley wave slowness and attenuation are affected by formation permeability. Both slowness and attenuation (1/Q) are observed to increase with formation permeability. This increase is frequency dependent, being greatest at low frequencies. The presence of simulated mudcakes on the borehole wall reduces the permeability effect on Stoneley waves, but does not eliminate it. The mudcake effect is frequency dependent, being greatest at low frequencies. In our experiments on rocks, the laboratory data is in qualitative agreement with theoretical predictions. In a very well characterized synthetic porous material, theory and experiment are in good quantitative agreement

  15. Octopus microvasculature: permeability to ferritin and carbon.

    Science.gov (United States)

    Browning, J

    1979-01-01

    The permeability of Octopus microvasculature was investigated by intravascular injection of carbon and ferritin. Vessels were tight to carbon while ferritin penetrated the pericyte junction, and was found extravascularly 1-2 min after its introduction. Vesicles occurred rarely in pericytes; fenestrae were absent. The discontinuous endothelial layer did not consitute a permeability barrier. The basement membrane, although retarding the movement of ferritin, was permeable to it; carbon did not penetrate the basement membrane. Evidence indicated that ferritin, and thus similarly sized and smaller water soluble materials, traverse the pericyte junction as a result of bulk fluid flow. Comparisons are made with the convective (or junctional) and slower, diffusive (or vesicular) passage of materials known to occur across the endothelium of continuous capillaries in mammals. Previous macrophysiological determinations concerning the permeability of Octopus vessels are questioned in view of these findings. Possible reasons for some major structural differences in the microcirculatory systems of cephalopods and vertebrates are briefly discussed.

  16. Dentin Permeability of Carious Primary Teeth

    African Journals Online (AJOL)

    primary dental pulp make it difficult to determine which modality offers the best ... The most common pathology of the dentine is dental caries. ... to evaluate dentine permeability is to calculate its hydraulic conductance (Lp) using fluid filtration ...

  17. Permeability of gypsum samples dehydrated in air

    Science.gov (United States)

    Milsch, Harald; Priegnitz, Mike; Blöcher, Guido

    2011-09-01

    We report on changes in rock permeability induced by devolatilization reactions using gypsum as a reference analog material. Cylindrical samples of natural alabaster were dehydrated in air (dry) for up to 800 h at ambient pressure and temperatures between 378 and 423 K. Subsequently, the reaction kinetics, so induced changes in porosity, and the concurrent evolution of sample permeability were constrained. Weighing the heated samples in predefined time intervals yielded the reaction progress where the stoichiometric mass balance indicated an ultimate and complete dehydration to anhydrite regardless of temperature. Porosity showed to continuously increase with reaction progress from approximately 2% to 30%, whilst the initial bulk volume remained unchanged. Within these limits permeability significantly increased with porosity by almost three orders of magnitude from approximately 7 × 10-19 m2 to 3 × 10-16 m2. We show that - when mechanical and hydraulic feedbacks can be excluded - permeability, reaction progress, and porosity are related unequivocally.

  18. Permeability After Impact Testing of Composite Laminates

    Science.gov (United States)

    Nettles, Alan T.

    2003-01-01

    Since composite laminates are beginning to be identified for use in reusable launch vehicle propulsion systems, an understanding of their permeance is needed. A foreign object impact event can cause a localized area of permeability (leakage) in a polymer matrix composite and it is the aim of this study to assess a method of quantifying permeability-after-impact results. A simple test apparatus is presented and variables that could affect the measured values of permeability-after-impact were assessed. Once it was determined that valid numbers were being measured, a fiber/resin system was impacted at various impact levels and the resulting permeability measured, first with a leak check solution (qualitative) then using the new apparatus (quantitative). The results showed that as the impact level increased, so did the measured leakage. As the pressure to the specimen was increased, the leak rate was seen to increase in a non-linear fashion for almost all of the specimens tested.

  19. Surface sedimentation at permeable pavement systems

    DEFF Research Database (Denmark)

    Støvring, Jan; Dam, Torben; Jensen, Marina Bergen

    2018-01-01

    Newly installed permeable pavement (PP) systems provide high surface infiltration capacity, but the accumulation of sediments causes a decrease in capacity over time, eventually leading to surface clogging. With the aim of investigating local sedimentation processes and the importance of restorat......Newly installed permeable pavement (PP) systems provide high surface infiltration capacity, but the accumulation of sediments causes a decrease in capacity over time, eventually leading to surface clogging. With the aim of investigating local sedimentation processes and the importance...

  20. Negative permeability from random particle composites

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Shahid, E-mail: shussain2@qinetiq.com

    2017-04-15

    Artificial media, such as those composed of periodically-spaced wires for negative permittivity and split ring resonators for negative permeability have been extensively investigated for negative refractive index (NRI) applications (Smith et al., 2004; Pendry et al., 1999) [1,2]. This paper presents an alternative method for producing negative permeability: granular (or particulate) composites incorporating magnetic fillers. Artificial media, such as split-ring resonators, are designed to produce a magnetic resonance feature, which results in negative permeability over a narrow frequency range about the resonance frequency. The position of the feature is dependent upon the size of the inclusion. The material in this case is anisotropic, such that the feature is only observable when the materials are orientated in a specific direction relative to the applied field. A similar resonance can be generated in magnetic granular (particulate) materials: ferromagnetic resonance from the natural spin resonance of particles. Although the theoretical resonance profiles in granular composites shows the permeability dipping to negative values, this is rarely observed experimentally due to resonance damping effects. Results are presented for iron in spherical form and in flake form, dispersed in insulating host matrices. The two particle shapes show different permeability performance, with the magnetic flakes producing a negative contribution. This is attributed to the stronger coupling with the magnetic field resulting from the high aspect ratio of the flakes. The accompanying ferromagnetic resonance is strong enough to overcome the effects of damping and produce negative permeability. The size of random particle composites is not dictated by the wavelength of the applied field, so the materials are potentially much thinner than other, more traditional artificial composites at microwave frequencies. - Highlights: • Negative permeability from random particle composites is

  1. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

    Science.gov (United States)

    Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni; Lupia, Enrico

    2017-01-01

    CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

  2. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

    Directory of Open Access Journals (Sweden)

    Sophie Doublier

    Full Text Available CD40/CD40 ligand (CD40L dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs. We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS, and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS, and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

  3. Effects of fibrin adhesive material (Tissucol) on alveolar healing in rats under stress.

    OpenAIRE

    Alves-Rezende, Maria C. R. [UNESP; Okamoto, Tetuo [UNESP

    1997-01-01

    The effects of Tissucol on alveolar healing following stress were evaluated histologically, comparing three groups of 28 male albino rats each. Stress was applied and their right upper incisors were extracted. Group A served as an empty control site. In Group B, Tissucol was applied into the alveolar cavity. Group C received local antifibrinolytic treatment (alveolar irrigation with epsilon-aminocaproic acid solution) before implant of Tissucol into the tooth socket. Four animals in each grou...

  4. Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

    Science.gov (United States)

    Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

    2013-01-01

    Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from 8 CF subjects and 8 healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared to controls. CF subjects had lower serum and BAL IGF-1 levels compared to healthy controls. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, while IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo, results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment. PMID:23698746

  5. Transformable ferroelectric control of dynamic magnetic permeability

    Science.gov (United States)

    Jiang, Changjun; Jia, Chenglong; Wang, Fenglong; Zhou, Cai; Xue, Desheng

    2018-02-01

    Magnetic permeability, which measures the response of a material to an applied magnetic field, is crucial to the performance of magnetic devices and related technologies. Its dynamic value is usually a complex number with real and imaginary parts that describe, respectively, how much magnetic power can be stored and lost in the material. Control of permeability is therefore closely related to energy redistribution within a magnetic system or energy exchange between magnetic and other degrees of freedom via certain spin-dependent interactions. To avoid a high power consumption, direct manipulation of the permeability with an electric field through magnetoelectric coupling leads to high efficiency and simple operation, but remains a big challenge in both the fundamental physics and material science. Here we report unambiguous evidence of ferroelectric control of dynamic magnetic permeability in a Co /Pb (Mg1/3Nb2/3) 0.7Ti0.3O3 (Co/PMN-PT) heterostructure, in which the ferroelectric PMN-PT acts as an energy source for the ferromagnetic Co film via an interfacial linear magnetoelectric interaction. The electric field tuning of the magnitude and line shape of the permeability offers a highly localized means of controlling magnetization with ultralow power consumption. Additionally, the emergence of negative permeability promises a new way of realizing functional nanoscale metamaterials with adjustable refraction index.

  6. Defining clogging potential for permeable concrete.

    Science.gov (United States)

    Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

    2018-08-15

    Permeable concrete is used to reduce urban flooding as it allows water to flow through normally impermeable infrastructure. It is prone to clogging by particulate matter and predicting the long-term performance of permeable concrete is challenging as there is currently no reliable means of characterising clogging potential. This paper reports on the performance of a range of laboratory-prepared and commercial permeable concretes, close packed glass spheres and aggregate particles of varying size, exposed to different clogging methods to understand this phenomena. New methods were developed to study clogging and define clogging potential. The tests involved applying flowing water containing sand and/or clay in cycles, and measuring the change in permeability. Substantial permeability reductions were observed in all samples, particularly when exposed to sand and clay simultaneously. Three methods were used to define clogging potential based on measuring the initial permeability decay, half-life cycle and number of cycles to full clogging. We show for the first time strong linear correlations between these parameters for a wide range of samples, indicating their use for service-life prediction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Accurate control testing for clay liner permeability

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, R J

    1991-08-01

    Two series of centrifuge tests were carried out to evaluate the use of centrifuge modelling as a method of accurate control testing of clay liner permeability. The first series used a large 3 m radius geotechnical centrifuge and the second series a small 0.5 m radius machine built specifically for research on clay liners. Two permeability cells were fabricated in order to provide direct data comparisons between the two methods of permeability testing. In both cases, the centrifuge method proved to be effective and efficient, and was found to be free of both the technical difficulties and leakage risks normally associated with laboratory permeability testing of fine grained soils. Two materials were tested, a consolidated kaolin clay having an average permeability coefficient of 1.2{times}10{sup -9} m/s and a compacted illite clay having a permeability coefficient of 2.0{times}10{sup -11} m/s. Four additional tests were carried out to demonstrate that the 0.5 m radius centrifuge could be used for linear performance modelling to evaluate factors such as volumetric water content, compaction method and density, leachate compatibility and other construction effects on liner leakage. The main advantages of centrifuge testing of clay liners are rapid and accurate evaluation of hydraulic properties and realistic stress modelling for performance evaluations. 8 refs., 12 figs., 7 tabs.

  8. Cell permeability beyond the rule of 5.

    Science.gov (United States)

    Matsson, Pär; Doak, Bradley C; Over, Björn; Kihlberg, Jan

    2016-06-01

    Drug discovery for difficult targets that have large and flat binding sites is often better suited to compounds beyond the "rule of 5" (bRo5). However, such compounds carry higher pharmacokinetic risks, such as low solubility and permeability, and increased efflux and metabolism. Interestingly, recent drug approvals and studies suggest that cell permeable and orally bioavailable drugs can be discovered far into bRo5 space. Tactics such as reduction or shielding of polarity by N-methylation, bulky side chains and intramolecular hydrogen bonds may be used to increase cell permeability in this space, but often results in decreased solubility. Conformationally flexible compounds can, however, combine high permeability and solubility, properties that are keys for cell permeability and intestinal absorption. Recent developments in computational conformational analysis will aid design of such compounds and hence prediction of cell permeability. Transporter mediated efflux occurs for most investigated drugs in bRo5 space, however it is commonly overcome by high local intestinal concentrations on oral administration. In contrast, there is little data to support significant impact of transporter-mediated intestinal absorption in bRo5 space. Current knowledge of compound properties that govern transporter effects of bRo5 drugs is limited and requires further fundamental and comprehensive studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Comparative field permeability measurement of permeable pavements using ASTM C1701 and NCAT permeameter methods.

    Science.gov (United States)

    Li, Hui; Kayhanian, Masoud; Harvey, John T

    2013-03-30

    Fully permeable pavement is gradually gaining support as an alternative best management practice (BMP) for stormwater runoff management. As the use of these pavements increases, a definitive test method is needed to measure hydraulic performance and to evaluate clogging, both for performance studies and for assessment of permeability for construction quality assurance and maintenance needs assessment. Two of the most commonly used permeability measurement tests for porous asphalt and pervious concrete are the National Center for Asphalt Technology (NCAT) permeameter and ASTM C1701, respectively. This study was undertaken to compare measured values for both methods in the field on a variety of permeable pavements used in current practice. The field measurements were performed using six experimental section designs with different permeable pavement surface types including pervious concrete, porous asphalt and permeable interlocking concrete pavers. Multiple measurements were performed at five locations on each pavement test section. The results showed that: (i) silicone gel is a superior sealing material to prevent water leakage compared with conventional plumbing putty; (ii) both methods (NCAT and ASTM) can effectively be used to measure the permeability of all pavement types and the surface material type will not impact the measurement precision; (iii) the permeability values measured with the ASTM method were 50-90% (75% on average) lower than those measured with the NCAT method; (iv) the larger permeameter cylinder diameter used in the ASTM method improved the reliability and reduced the variability of the measured permeability. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Influence of local tetracycline on the microbiota of alveolar osteitis in rats

    OpenAIRE

    Bosco, Joseane Maria Dias; Oliveira, Sérgio Ricardo de; Bosco, Álvaro Francisco; Schweitzer, Christiane Marie; Jardim Júnior, Elerson Gaetti

    2008-01-01

    The aim of the present study was to evaluate the effects of local tetracycline on the occurrence of alveolar osteitis in rats, and on the microbiota associated to this infection. Forty Wistar rats were randomly assigned to 4 groups (n=10): I - the rats had the maxillary right incisor extracted and the alveolar wound did not receive any treatment; II - adrenaline and Ringer-PRAS were introduced into the alveolar wound; III - the alveolar wound was irrigated with sterile saline; and IV - the al...

  11. Perawatan Ortodonti pada Kasus Mutilasi dengan Resorpsi Tulang Alveolar dan Resesi Gingiva (Laporan Kasus

    Directory of Open Access Journals (Sweden)

    Retno Widayati

    2015-09-01

    Full Text Available In the mutilated case in adults, generally malocclusion is often accompanied by less support of periodontal tissues, such as alveolar bone resorption and gingival recession. The treatment of orthodontic is to arrange the teeth into good position and good occlusion, but is widely known to increase the alveolar bone resorption. In handling such case, orthodontist needs to look at factors which do not increase existing alveolar bone resorption and gingival recession. In this case report, it will be reported orthodontic treatment on mutilated case which are accompanied by alveolar bone resorption and gingival recession on a patient of 45 years and 4 months of age.

  12. Sodium selectivity of Reissner's membrane epithelial cells

    Directory of Open Access Journals (Sweden)

    Kim Kyunghee X

    2011-02-01

    Full Text Available Abstract Background Sodium absorption by Reissner's membrane is thought to contribute to the homeostasis of the volume of cochlear endolymph. It was previously shown that the absorptive transepithelial current was blocked by amiloride and benzamil. The most commonly-observed target of these drugs is the epithelial sodium channel (ENaC, which is composed of the three subunits α-,β- and γ-ENaC. However, other less-selective cation channels have also been observed to be sensitive to benzamil and amiloride. The aim of this study was to determine whether Reissner's membrane epithelial cells could support parasensory K+ absorption via amiloride- and benzamil-sensitive electrogenic pathways. Results We determined the molecular and functional expression of candidate cation channels with gene array (GEO GSE6196, RT-PCR, and whole-cell patch clamp. Transcript expression analysis of Reissner's membrane detected no amiloride-sensitive acid-sensing ion channels (ASIC1a, ASIC2a, ASIC2b nor amiloride-sensitive cyclic-nucleotide gated channels (CNGA1, CNGA2, CNGA4, CNGB3. By contrast, α-,β- and γ-ENaC were all previously reported as present in Reissner's membrane. The selectivity of the benzamil-sensitive cation currents was observed in whole-cell patch clamp recordings under Cl--free conditions where cations were the only permeant species. The currents were carried by Na+ but not K+, and the permeability of Li+ was greater than that of Na+ in Reissner's membrane. Complete replacement of bath Na+ with the inpermeable cation NMDG+ led to the same inward current as with benzamil in a Na+ bath. Conclusions These results are consistent with the amiloride/benzamil-sensitive absorptive flux of Reissner's membrane mediated by a highly Na+-selective channel that has several key characteristics in common with αβγ-ENaC. The amiloride-sensitive pathway therefore absorbs only Na+ in this epithelium and does not provide a parasensory K+ efflux route from scala

  13. Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse.

    Science.gov (United States)

    Lax, Siân; Rayes, Julie; Wichaiyo, Surasak; Haining, Elizabeth J; Lowe, Kate; Grygielska, Beata; Laloo, Ryan; Flodby, Per; Borok, Zea; Crandall, Edward D; Thickett, David R; Watson, Steve P

    2017-12-01

    There is no therapeutic intervention proven to prevent acute respiratory distress syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes that occur during ARDS; however, the mechanisms remain elusive. The platelet receptor CLEC-2 has been shown to regulate vascular integrity at sites of acute inflammation. Therefore the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS. Platelet-specific CLEC-2-deficient, as well as alveolar epithelial type I cell (AECI)-specific or hematopoietic-specific podoplanin deficient, mice were established using cre-loxP strategies. Combining these with intratracheal (IT) instillations of lipopolysaccharide (LPS), we demonstrate that arterial oxygen saturation decline in response to IT-LPS in platelet-specific CLEC-2-deficient mice is significantly augmented. An increase in bronchoalveolar lavage (BAL) neutrophils and protein was also observed 48 h post-IT-LPS, with significant increases in pro-inflammatory chemokines detected in BAL of platelet-specific CLEC-2-deficient animals. Deletion of podoplanin from hematopoietic cells but not AECIs also reduces lung function and increases pro-inflammatory chemokine expression following IT-LPS. Furthermore, we demonstrate that following IT-LPS, platelets are present in BAL in aggregates with neutrophils, which allows for CLEC-2 interaction with podoplanin expressed on BAL inflammatory alveolar macrophages. Taken together, these data suggest that the platelet CLEC-2-podoplanin signaling axis regulates the severity of lung inflammation in mice and is a possible novel target for therapeutic intervention in patients at risk of developing ARDS. Copyright © 2017 the American Physiological Society.

  14. Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Jabaudon, Matthieu; Blondonnet, Raiko; Roszyk, Laurence; Bouvier, Damien; Audard, Jules; Clairefond, Gael; Fournier, Mathilde; Marceau, Geoffroy; Déchelotte, Pierre; Pereira, Bruno; Sapin, Vincent; Constantin, Jean-Michel

    2015-07-15

    Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date. To verify whether sRAGE could predict AFC during ARDS. Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS. The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P < 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P < 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved. Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with www.clinicaltrials.gov (NCT 00811629).

  15. Controlling DC permeability in cast steels

    International Nuclear Information System (INIS)

    Sumner, Aaran; Gerada, Chris; Brown, Neil; Clare, Adam

    2017-01-01

    Annealing (at multiple cooling rates) and quenching (with tempering) was performed on specimens of cast steel of varying composition. The aim was to devise a method for selecting the steel with the highest permeability, from any given range of steels, and then increasing the permeability by heat treatment. Metallographic samples were imaged using optical microscopy to show the effect of the applied heat treatments on the microstructure. Commonly cast steels can have DC permeability altered by the careful selection of a heat treatment. Increases of up to 381% were achieved by annealing using a cooling rate of 6.0 °C/min. Annealing was found to cause the carbon present in the steel to migrate from grain boundaries and from within ferrite crystals into adjacent pearlite crystals. The migration of the carbon resulted in less carbon at grain boundaries and within ferrite crystals reducing the number of pinning sites between magnetic domains. This gives rise to a higher permeability. Quenching then tempering was found to cause the formation of small ferrite crystals with the carbon content of the steel predominately held in the martensitic crystal structures. The results show that with any given range of steel compositions the highest baseline DC permeability will be found with the steel that has the highest iron content and the lowest carbon content. For the samples tested in this paper a cooling rate of 4.5 °C/min resulted in the relative permeability of the sample with the highest baseline permeability, AS4, increasing from 783 to 1479 at 0.5 T. This paper shows how heat treatments commonly applied to hypoeutectoid cast steels, to improve their mechanical performance, can be used to also enhance electromagnetic properties of these alloys. The use of cast steels allows the creation of DC components for electrical machines not possible by the widely used method of stacking of electrical grade sheet steels. - Highlights: • A range of structural steels had their

  16. Controlling DC permeability in cast steels

    Energy Technology Data Exchange (ETDEWEB)

    Sumner, Aaran, E-mail: aaran.sumner@nottingham.ac.uk [University of Nottingham, Nottingham University Park Campus, Nottingham NG7 2RD, England (United Kingdom); Gerada, Chris, E-mail: chris.gerada@nottingham.ac.uk [Electrical Machines, University of Nottingham, Tower Building, Nottingham NG7 2RD, England (United Kingdom); Brown, Neil, E-mail: neil.brown@cummins.com [Advanced Electrical Machines Research and Technology at Cummins Power Generation, Peterborough PE2 6FZ, England (United Kingdom); Clare, Adam, E-mail: adam.clare@nottingham.ac.uk [Advanced Manufacturing, University of Nottingham, University Park Campus, Nottingham NG7 2RD, England (United Kingdom)

    2017-05-01

    Annealing (at multiple cooling rates) and quenching (with tempering) was performed on specimens of cast steel of varying composition. The aim was to devise a method for selecting the steel with the highest permeability, from any given range of steels, and then increasing the permeability by heat treatment. Metallographic samples were imaged using optical microscopy to show the effect of the applied heat treatments on the microstructure. Commonly cast steels can have DC permeability altered by the careful selection of a heat treatment. Increases of up to 381% were achieved by annealing using a cooling rate of 6.0 °C/min. Annealing was found to cause the carbon present in the steel to migrate from grain boundaries and from within ferrite crystals into adjacent pearlite crystals. The migration of the carbon resulted in less carbon at grain boundaries and within ferrite crystals reducing the number of pinning sites between magnetic domains. This gives rise to a higher permeability. Quenching then tempering was found to cause the formation of small ferrite crystals with the carbon content of the steel predominately held in the martensitic crystal structures. The results show that with any given range of steel compositions the highest baseline DC permeability will be found with the steel that has the highest iron content and the lowest carbon content. For the samples tested in this paper a cooling rate of 4.5 °C/min resulted in the relative permeability of the sample with the highest baseline permeability, AS4, increasing from 783 to 1479 at 0.5 T. This paper shows how heat treatments commonly applied to hypoeutectoid cast steels, to improve their mechanical performance, can be used to also enhance electromagnetic properties of these alloys. The use of cast steels allows the creation of DC components for electrical machines not possible by the widely used method of stacking of electrical grade sheet steels. - Highlights: • A range of structural steels had their

  17. Environmentally determined differences in the murine lung microbiota and their relation to alveolar architecture.

    Directory of Open Access Journals (Sweden)

    Yeojun Yun

    Full Text Available Commensal bacteria control the micro-ecology of metazoan epithelial surfaces with pivotal effect on tissue homeostasis and host defense. In contrast to the upper respiratory tract, the lower respiratory tract of healthy individuals has largely been considered free of microorganisms. To understand airway micro-ecology we studied microbiota of sterilely excised lungs from mice of different origin including outbred wild mice caught in the natural environment or kept under non-specific-pathogen-free (SPF conditions as well as inbred mice maintained in non-SPF, SPF or germ-free (GF facilities. High-throughput pyrosequencing of reverse transcribed 16S rRNA revealed metabolically active murine lung microbiota in all but GF mice. The overall composition across samples was similar at the phylum and family level. However, species richness was significantly different between lung microbiota from SPF and non-SPF mice. Non-cultivatable Betaproteobacteria such as Ralstonia spp. made up the major constituents and were also confirmed by 16S rRNA gene cloning analysis. Additionally, Pasteurellaceae, Enterobacteria and Firmicutes were isolated from lungs of non-SPF mice. Bacterial communities were detectable by fluorescent in situ hybridization (FISH at alveolar epithelia in the absence of inflammation. Notably, higher bacterial abundance in non-SPF mice correlated with more and smaller size alveolae, which was corroborated by transplanting Lactobacillus spp. lung isolates into GF mice. Our data indicate a common microbial composition of murine lungs, which is diversified through different environmental conditions and affects lung architecture. Identification of the microbiota of murine lungs will pave the path to study their influence on pulmonary immunity to infection and allergens using mouse models.

  18. Determination of the mean transit time for the transport of aerosolized 99mTc-DTPA across the pulmonary epithelial membrane. A plasma sample method

    DEFF Research Database (Denmark)

    Groth, Sofie; Lassen, N A; Rossing, Niels Nygaard

    1988-01-01

    During the last decade it has been customary to estimate pulmonary epithelial permeability (P-P) as the pulmonary clearance of inhaled nebulized 99mTc-DTPA from a time-activity (t-a) curve registered externally by monitoring over the chest. The t-a curve, however, is not defined by the degree of ...

  19. Vectorial transcytosis of dimeric IgA by the Calu-3 human lung epithelial cell line: upregulation by IFN-gamma

    NARCIS (Netherlands)

    Loman, S.; Radl, J.; Jansen, H. M.; Out, T. A.; Lutter, R.

    1997-01-01

    We have developed an in vitro airway epithelial cell model for dimeric immunoglobulin (Ig) A (dIgA) transcytosis that allows the assessment of polymeric Ig receptor (pIgR) gene expression and actual dIgA transport. Tight monolayers of human lung-derived Calu-3 adenocarcinoma cells grown on permeable

  20. Bactericidal Permeability-Increasing Proteins Shape Host-Microbe Interactions

    Directory of Open Access Journals (Sweden)

    Fangmin Chen

    2017-04-01

    Full Text Available We characterized bactericidal permeability-increasing proteins (BPIs of the squid Euprymna scolopes, EsBPI2 and EsBPI4. They have molecular characteristics typical of other animal BPIs, are closely related to one another, and nest phylogenetically among invertebrate BPIs. Purified EsBPIs had antimicrobial activity against the squid’s symbiont, Vibrio fischeri, which colonizes light organ crypt epithelia. Activity of both proteins was abrogated by heat treatment and coincubation with specific antibodies. Pretreatment under acidic conditions similar to those during symbiosis initiation rendered V. fischeri more resistant to the antimicrobial activity of the proteins. Immunocytochemistry localized EsBPIs to the symbiotic organ and other epithelial surfaces interacting with ambient seawater. The proteins differed in intracellular distribution. Further, whereas EsBPI4 was restricted to epithelia, EsBPI2 also occurred in blood and in a transient juvenile organ that mediates hatching. The data provide evidence that these BPIs play different defensive roles early in the life of E. scolopes, modulating interactions with the symbiont.

  1. Increased gut permeability in cancer cachexia: mechanisms and clinical relevance.

    Science.gov (United States)

    Bindels, Laure B; Neyrinck, Audrey M; Loumaye, Audrey; Catry, Emilie; Walgrave, Hannah; Cherbuy, Claire; Leclercq, Sophie; Van Hul, Matthias; Plovier, Hubert; Pachikian, Barbara; Bermúdez-Humarán, Luis G; Langella, Philippe; Cani, Patrice D; Thissen, Jean-Paul; Delzenne, Nathalie M

    2018-04-06

    Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium ( Faecalibacterium prausnitzii ) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis.

  2. The effect of topical treatments for CRS on the sinonasal epithelial barrier.

    Science.gov (United States)

    Ramezanpour, M; Rayan, A; Smith, J L P; Vreugde, S

    2017-06-01

    Several topical treatments are used in the management of Chronic Rhinosinusitis (CRS), some of which the safety and efficacy has yet to be determined. The purpose of this study was to investigate the effect of commonly used topical treatments on the sinonasal epithelial barrier. Normal saline (0.9% Sodium Chloride), hypertonic saline (3% Sodium Chloride), FESS Sinu-Cleanse Hypertonic, FLO Sinus Care and Budesonide 1 mg/ 2 ml were applied to the apical side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS patients (n=3) and non-CRS controls (n=3) for 24 hours. Epithelial barrier structure and function was assessed using trans-epithelial electrical resistance (TEER), measuring the passage of Fluorescein Isothiocyanate labelled Dextrans (FITC-Dextrans) and assessing the expression of the tight junction protein Zona Occludens-1 (ZO-1) using immunofluorescence. Toxicity was assessed using a Lactate Dehydrogenase (LDH) assay. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Hypertonic solution and budesonide significantly increased TEER values in CRS derived HNECs. In contrast, FESS Sinu-Cleanse Hypertonic significantly reduced TEER 5 minutes after application of the solution followed by an increase in paracellular permeability of FITC-Dextrans (30 minutes) and increased LDH levels 6 hours after application of the solution. Our findings confirm that isotonic and hypertonic saline solutions do not compromise epithelial barrier function in vitro but underscore the importance of examining safety and efficacy of over-the-counter wash solutions.

  3. Translocation of SiO2-NPs across in vitro human bronchial epithelial monolayer

    International Nuclear Information System (INIS)

    George, I; Vranic, S; Boland, S; Borot, M C; Marano, F; Baeza-Squiban, A

    2013-01-01

    Safe development and application of nanotechnologies in many fields require better knowledge about their potential adverse effects on human health. Evidence of abilities of nanoparticles (NPs) to cross epithelial barriers and reach secondary organs via the bloodstream led us to investigate the translocation of SiO 2 NPs of 50 nm (50 nm-SiO 2 -NPs) across human bronchial epithelial cells that are primary targets after exposure to inhaled NPs. We quantified the translocation of fluorescently labelled SiO 2 NPs at non-cytotoxic concentrations (5 and 10 μg/cm 2 ) across Calu-3 epithelial monolayer. After 14 days in culture Calu-3 cells seeded onto 3 μm-polycarbonate Transwell membranes formed an efficient bronchial barrier assessed by measurement of the transepithelial electric resistance and quantification of the permeability of the monolayer. After 24 hours of exposure, we observed a significant translocation of NPs that was more important when the initial NP concentration decreased. Confocal microscopy observations revealed NP uptake by cells and an important NP retention inside the porous membrane. In conclusion, 50 nm-SiO 2 -NPs can cross the human bronchial epithelial barrier without affecting the integrity of the epithelial cell monolayer.

  4. Free-floating epithelial micro-tissue arrays: a low cost and versatile technique.

    Science.gov (United States)

    Flood, P; Alvarez, L; Reynaud, E G

    2016-10-11

    Three-dimensional (3D) tissue models are invaluable tools that can closely reflect the in vivo physiological environment. However, they are usually difficult to develop, have a low throughput and are often costly; limiting their utility to most laboratories. The recent availability of inexpensive additive manufacturing printers and open source 3D design software offers us the possibility to easily create affordable 3D cell culture platforms. To demonstrate this, we established a simple, inexpensive and robust method for producing arrays of free-floating epithelial micro-tissues. Using a combination of 3D computer aided design and 3D printing, hydrogel micro-moulding and collagen cell encapsulation we engineered microenvironments that consistently direct the growth of micro-tissue arrays. We described the adaptability of this technique by testing several immortalised epithelial cell lines (MDCK, A549, Caco-2) and by generating branching morphology and micron to millimetre scaled micro-tissues. We established by fluorescence and electron microscopy that micro-tissues are polarised, have cell type specific differentiated phenotypes and regain native in vivo tissue qualities. Finally, using Salmonella typhimurium we show micro-tissues display a more physiologically relevant infection response compared to epithelial monolayers grown on permeable filter supports. In summary, we have developed a robust and adaptable technique for producing arrays of epithelial micro-tissues. This in vitro model has the potential to be a valuable tool for studying epithelial cell and tissue function/architecture in a physiologically relevant context.

  5. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression

    International Nuclear Information System (INIS)

    Pinton, Philippe; Nougayrede, Jean-Philippe; Del Rio, Juan-Carlos; Moreno, Carolina; Marin, Daniela E.; Ferrier, Laurent; Bracarense, Ana-Paula; Kolf-Clauw, Martine; Oswald, Isabelle P.

    2009-01-01

    'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.

  6. Metabolic shift in lung alveolar cell mitochondria following acrolein exposure.

    Science.gov (United States)

    Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

    2013-11-15

    Acrolein, an α,β unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A2 activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants.

  7. Anesthetic technique for inferior alveolar nerve block: a new approach

    Directory of Open Access Journals (Sweden)

    Dafna Geller Palti

    2011-02-01

    Full Text Available BACKGROUND: Effective pain control in Dentistry may be achieved by local anesthetic techniques. The success of the anesthetic technique in mandibular structures depends on the proximity of the needle tip to the mandibular foramen at the moment of anesthetic injection into the pterygomandibular region. Two techniques are available to reach the inferior alveolar nerve where it enters the mandibular canal, namely indirect and direct; these techniques differ in the number of movements required. Data demonstrate that the indirect technique is considered ineffective in 15% of cases and the direct technique in 13-29% of cases. OBJECTIVE: The aim of this study was to describe an alternative technique for inferior alveolar nerve block using several anatomical points for reference, simplifying the procedure and enabling greater success and a more rapid learning curve. MATERIAL AND METHODS: A total of 193 mandibles (146 with permanent dentition and 47 with primary dentition from dry skulls were used to establish a relationship between the teeth and the mandibular foramen. By using two wires, the first passing through the mesiobuccal groove and middle point of the mesial slope of the distolingual cusp of the primary second molar or permanent first molar (right side, and the second following the oclusal plane (left side, a line can be achieved whose projection coincides with the left mandibular foramen. RESULTS: The obtained data showed correlation in 82.88% of cases using the permanent first molar, and in 93.62% of cases using the primary second molar. CONCLUSION: This method is potentially effective for inferior alveolar nerve block, especially in Pediatric Dentistry.

  8. Anesthetic technique for inferior alveolar nerve block: a new approach

    Science.gov (United States)

    PALTI, Dafna Geller; de ALMEIDA, Cristiane Machado; RODRIGUES, Antonio de Castro; ANDREO, Jesus Carlos; LIMA, José Eduardo Oliveira

    2011-01-01

    Background Effective pain control in Dentistry may be achieved by local anesthetic techniques. The success of the anesthetic technique in mandibular structures depends on the proximity of the needle tip to the mandibular foramen at the moment of anesthetic injection into the pterygomandibular region. Two techniques are available to reach the inferior alveolar nerve where it enters the mandibular canal, namely indirect and direct; these techniques differ in the number of movements required. Data demonstrate that the indirect technique is considered ineffective in 15% of cases and the direct technique in 1329% of cases. Objective Objective: The aim of this study was to describe an alternative technique for inferior alveolar nerve block using several anatomical points for reference, simplifying the procedure and enabling greater success and a more rapid learning curve. Materials and Methods A total of 193 mandibles (146 with permanent dentition and 47 with primary dentition) from dry skulls were used to establish a relationship between the teeth and the mandibular foramen. By using two wires, the first passing through the mesiobuccal groove and middle point of the mesial slope of the distolingual cusp of the primary second molar or permanent first molar (right side), and the second following the oclusal plane (left side), a line can be achieved whose projection coincides with the left mandibular foramen. Results The obtained data showed correlation in 82.88% of cases using the permanent first molar, and in 93.62% of cases using the primary second molar. Conclusion This method is potentially effective for inferior alveolar nerve block, especially in Pediatric Dentistry. PMID:21437463

  9. Transient Amaurosis and Diplopia After Inferior Alveolar Nerve Block.

    Science.gov (United States)

    Odabaşi, Onur; Şahin, Onur; Polat, Mehmet Emrah

    2017-10-01

    A 40-year-old female patient was admitted to the authors' oral and maxillofacial clinic for removal of her lower left second molar under local anesthesia. The patient's medical history revealed that she had cardiac arhythmia and hypertension. Inferior alveolar nerve block was achieved using 2 mL of sefacaine (%3 mepivacaine HCL, without epinephrine). The patient complained of loss of vision in her left eye. All procedures were stopped immediately. Within 2 minutes the patient reported diplopia. All of the symptoms disappeared about 5 minutes after initial observation. Follow-up after 1 day revealed no complications. The procedure was then performed uneventfully.

  10. Is acute alveolar dilation an indicator of strangulation homicide?

    DEFF Research Database (Denmark)

    Klysner, Anne; Lynnerup, Niels; Hougen, Hans Petter

    2011-01-01

    Some cases of suspected homicidal strangulation are difficult to diagnose if the classical injuries of strangulation are few or lacking. The main purpose of this study was to determine if abnormal distension of alveolar airspaces is present in strangulation deaths and whether or not it can be used...... to support this diagnosis. Another purpose was to see how often the gross examination of the lungs was in agreement with the microscopic examination. The material comprised 33 victims of homicidal strangulation above the age of 15 years, autopsied at the Department of Forensic Medicine in Copenhagen between...

  11. Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis

    Science.gov (United States)

    Goroshi, Manjunath; Lila, Anurag R.; Bandgar, Tushar; Shah, Nalini S.

    2018-01-01

    Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhancement in early arterial phase (unenhanced Hounsfield unit [HU]-45.3; arterial phase HU-158.2). 18- flurodeoxyglucose positron emission tomography/CT showed multiple lesions and was confirmed histologically to be due to ASPS. PMID:29398970

  12. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells