Non-genomic estrogen regulation of ion transport and airway surface liquid dynamics in cystic fibrosis bronchial epithelium.

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Vinciane Saint-Criq

Full Text Available Male cystic fibrosis (CF patients survive longer than females and lung exacerbations in CF females vary during the estrous cycle. Estrogen has been reported to reduce the height of the airway surface liquid (ASL in female CF bronchial epithelium. Here we investigated the effect of 17β-estradiol on the airway surface liquid height and ion transport in normal (NuLi-1 and CF (CuFi-1 bronchial epithelial monolayers. Live cell imaging using confocal microscopy revealed that airway surface liquid height was significantly higher in the non-CF cells compared to the CF cells. 17β-estradiol (0.1-10 nM reduced the airway surface liquid height in non-CF and CF cells after 30 min treatment. Treatment with the nuclear-impeded Estrogen Dendrimer Conjugate mimicked the effect of free estrogen by reducing significantly the airway surface liquid height in CF and non-CF cells. Inhibition of chloride transport or basolateral potassium recycling decreased the airway surface liquid height and 17β-estradiol had no additive effect in the presence of these ion transporter inhibitors. 17β-estradiol decreased bumetanide-sensitive transepithelial short-circuit current in non-CF cells and prevented the forskolin-induced increase in ASL height. 17β-estradiol stimulated an amiloride-sensitive transepithelial current and increased ouabain-sensitive basolateral short-circuit current in CF cells. 17β-estradiol increased PKCδ activity in CF and non-CF cells. These results demonstrate that estrogen dehydrates CF and non-CF ASL, and these responses to 17β-estradiol are non-genomic rather than involving the classical nuclear estrogen receptor pathway. 17β-estradiol acts on the airway surface liquid by inhibiting cAMP-mediated chloride secretion in non-CF cells and increasing sodium absorption via the stimulation of PKCδ, ENaC and the Na(+/K(+ATPase in CF cells.

Hypoxia-inducible factor-1 signalling promotes goblet cell hyperplasia in airway epithelium

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Polosukhin, Vasiliy V; Cates, Justin M; Lawson, William E; Milstone, Aaron P; Matafonov, Anton G; Massion, Pierre P; Lee, Jae Woo; Randell, Scott H; Blackwell, Timothy S

2018-01-01

Goblet cell hyperplasia is a common feature of chronic obstructive pulmonary disease (COPD) airways, but the mechanisms that underlie this epithelial remodelling in COPD are not understood. Based on our previous finding of hypoxia-inducible factor-1α (HIF-1α) nuclear localization in large airways from patients with COPD, we investigated whether hypoxia-inducible signalling could influence the development of goblet cell hyperplasia. We evaluated large airway samples obtained from 18 lifelong non-smokers and 13 former smokers without COPD, and 45 former smokers with COPD. In these specimens, HIF-1α nuclear staining occurred almost exclusively in COPD patients in areas of airway remodelling. In COPD patients, 93.2 ± 3.9% (range 65 – 100%) of goblet cells were HIF-1α positive in areas of goblet cell hyperplasia, whereas nuclear HIF-1α was not detected in individuals without COPD or in normal-appearing pseudostratified epithelium from COPD patients. To determine the direct effects of hypoxia-inducible signalling on epithelial cell differentiation in vitro, human bronchial epithelial cells (HBECs) were grown in air-liquid interface cultures under hypoxia (1% O2) or following treatment with a selective HIF-1α stabilizer, (2R)-[(4-biphenylylsulphonyl)amino]-N-hydroxy-3-phenyl-propionamide (BiPS). HBECs grown in hypoxia or with BiPS treatment were characterized by HIF-1α activation, carbonic anhydrase IX expression, mucus-producing cell hyperplasia and increased expression of MUC5AC. Analysis of signal transduction pathways in cells with HIF-1α activation showed increased ERK1/2 phosphorylation without activation of epidermal growth factor receptor, Ras, PI3K-Akt or STAT6. These data indicate an important effect of hypoxia-inducible signalling on airway epithelial cell differentiation and identify a new potential target to limit mucus production in COPD. PMID:21557221

SPDEF regulates goblet cell hyperplasia in the airway epithelium

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Park, Kwon-Sik; Korfhagen, Thomas R.; Bruno, Michael D.; Kitzmiller, Joseph A.; Wan, Huajing; Wert, Susan E.; Khurana Hershey, Gurjit K.; Chen, Gang; Whitsett, Jeffrey A.

2007-01-01

Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo. PMID:17347682

Dioscorin protects tight junction protein expression in A549 human airway epithelium cells from dust mite damage.

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Fu, Lin Shien; Ko, Ying Hsien; Lin, Kuo Wei; Hsu, Jeng Yuan; Chu, Jao Jia; Chi, Chin Shiang

2009-12-01

In addition to being an allergen, the trypsin activity of dust mite extract also destroys the tight junctions of bronchial epithelium. Such damage can lead to airway leakage, which increases airway exposure to allergens, irritants, and other pathogens. Dioscorin, the storage protein of yam, demonstrates anti-trypsin activity, as well as other potential anti-inflammatory effects. This study investigated the protective role of dioscorin for tight junctions. The immunofluorescence stains of zonula occludens (ZO-1), E-cadherin (EC) and desmoplakin (DP) proteins were compared. A cultured A549 cell line was used as a control and A549 cells were incubated with mite extract 100 mg/mL for 16 h, with or without dioscorin 100 mg/mL pretreatment for 8 h and with dioscorin 100 mg/mL alone for 16 h. Western blot was performed to detect changes in ZO-1, EC, and DP in the treated A549 cell lines. Loss of tight junction protein expression (ZO-1, EC, DP) was demonstrated after 16-h mite extract incubation. The defect could be restored if cells were pretreated with dioscorin for 8 h. In addition, dioscorin did not cause damage to the A549 cell lines in terms of cell survival or morphology. Western blot showed no change in the amount of tight junction protein under various conditions. Dioscorin is a potential protector of airway damage caused by mite extract.

Host Defense and the Airway Epithelium: Frontline Responses That Protect against Bacterial Invasion and Pneumonia

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Nicholas A. Eisele

2011-01-01

Full Text Available Airway epithelial cells are the first line of defense against invading microbes, and they protect themselves through the production of carbohydrate and protein matrices concentrated with antimicrobial products. In addition, they act as sentinels, expressing pattern recognition receptors that become activated upon sensing bacterial products and stimulate downstream recruitment and activation of immune cells which clear invading microbes. Bacterial pathogens that successfully colonize the lungs must resist these mechanisms or inhibit their production, penetrate the epithelial barrier, and be prepared to resist a barrage of inflammation. Despite the enormous task at hand, relatively few virulence factors coordinate the battle with the epithelium while simultaneously providing resistance to inflammatory cells and causing injury to the lung. Here we review mechanisms whereby airway epithelial cells recognize pathogens and activate a program of antibacterial pathways to prevent colonization of the lung, along with a few examples of how bacteria disrupt these responses to cause pneumonia.

Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

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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.

Human airway xenograft models of epithelial cell regeneration

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Puchelle Edith

2000-10-01

Full Text Available Abstract Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa.

Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

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GM Roomans

2010-06-01

Full Text Available Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a a ductal cell type in the submucosal glands of the proximal trachea, (b basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c variant Clara cells (Clarav-cells in the bronchioles and (d at the junctions between the bronchioles and the alveolar ducts, and (e alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a embryonic stem (ES cells, induced pluripotent stem (iPS cells, or amniotic fluid stem cells, (b side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF effects

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Jeffrey S. Fedan

2013-10-01

Full Text Available In asthmatic patients, inhalation of hyperosmolar saline or D-mannitol (D-M elicits bronchoconstriction, but in healthy subjects exercise causes bronchodilation. Hyperventilation causes drying of airway surface liquid (ASL and increases its osmolarity. Hyperosmolar challenge of airway epithelium releases epithelium-derived relaxing factor (EpDRF, which relaxes the airway smooth muscle. This pathway could be involved in exercise-induced bronchodilation. Little is known of ASL hyperosmolarity effects on epithelial function. We investigated the effects of osmolar challenge maneuvers on dispersed and adherent guinea-pig tracheal epithelial cells to examine the hypothesis that EpDRF-mediated relaxation is associated with epithelial cell shrinkage. Enzymatically-dispersed cells shrank when challenged with ≥10 mOsM added D M, urea or NaCl with a concentration-dependence that mimics relaxation of the of isolated, perfused tracheas (IPT. Cells shrank when incubated in isosmolar N-methyl-D-glucamine (NMDG chloride, Na gluconate (Glu, NMDG-Glu, K-Glu and K2SO4, and swelled in isosmolar KBr and KCl. However, isosmolar challenge is not a strong stimulus of relaxation in IPTs. In previous studies amiloride and 4,4' diisothiocyano 2,2' stilbenedisulfonic acid (DIDS inhibited relaxation of IPT to hyperosmolar challenge, but had little effect on shrinkage of dispersed cells. Confocal microscopy in tracheal segments showed that adherent epithelium is refractory to low hyperosmolar concentrations that induce dispersed cell shrinkage and relaxation of IPT. Except for gadolinium and erythro 9 (2 hydroxy 3 nonyladenine (EHNA, actin and microtubule inhibitors and membrane permeabilizing agents did not affect on ion transport by adherent epithelium or shrinkage responses of dispersed cells. Our studies dissociate relaxation of IPT from cell shrinkage after hyperosmolar challenge of airway epithelium .

Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

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Bernard, Alfred, E-mail: Alfred.bernard@uclouvain.be; Nickmilder, Marc; Dumont, Xavier

2015-07-15

It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial

Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

International Nuclear Information System (INIS)

Bernard, Alfred; Nickmilder, Marc; Dumont, Xavier

2015-01-01

It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial

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

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.

Repair of tracheal epithelium by basal cells after chlorine-induced injury

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Musah Sadiatu

2012-11-01

Full Text Available Abstract Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5 and keratin 14 (K14 for basal cells, Clara cell secretory protein (CCSP for Clara cells, and acetylated tubulin (AcTub for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10, but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion

Neuronal NOS localises to human airway cilia.

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Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

2015-01-30

Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of apoptosis in airway epithelium

International Nuclear Information System (INIS)

Alenzi, F.Q.

2009-01-01

Airway epithelial cells may play an important clinical role in the apoptosis of eosinophils. To study recognition pathways, two types of large bronchial airway epithelial cells were used (LAECs and A549). Both resting, and dexamethasone-stimulated epithelial cells, were used in an inhibition assay. Confocal microscopy was used to demonstrate engulfment of apoptotic eosinophils. Apoptotic eosinophils were recognized and phagocytosed by macrophages, and by LAECs. The ability of LAECs to engulf apoptotic eosinophils was enhanced by dexamethasone and interlukin-1 (IL-1beta). Inhibition by monoclonal antibodies (Mabs) prevented the uptake of apoptotic cells by LAECs. This study therefore suggests that LAECs are capable of recognizing and engulfing apoptotic eosinophils, and that this process is enhanced by IL-1 beta and dexamethasone. (author)

Trefoil factor-2 reverses airway remodeling changes in allergic airways disease.

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Royce, Simon G; Lim, Clarice; Muljadi, Ruth C; Samuel, Chrishan S; Ververis, Katherine; Karagiannis, Tom C; Giraud, Andrew S; Tang, Mimi L K

2013-01-01

Trefoil factor 2 (TFF2) is a small peptide with an important role in mucosal repair. TFF2 is up-regulated in asthma, suggesting a role in asthma pathogenesis. Given its known biological role in promoting epithelial repair, TFF2 might be expected to exert a protective function in limiting the progression of airway remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was investigated by examining the expression of TFF2 in the airway and lung, and evaluating the effects of recombinant TFF2 treatment on established airway remodeling in a murine model of chronic allergic airways disease (AAD). BALB/c mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks, whereas mice with established OVA-induced AAD were treated with TFF2 or vehicle control (intranasally for 14 d). Effects on airway remodeling, airway inflammation, and airway hyperresponsiveness were then assessed, whereas TFF2 expression was determined by immunohistochemistry. TFF2 expression was significantly increased in the airways of mice with AAD, compared with expression levels in control mice. TFF2 treatment resulted in reduced epithelial thickening, subepithelial collagen deposition, goblet-cell metaplasia, bronchial epithelium apoptosis, and airway hyperresponsiveness (all P < 0.05, versus vehicle control), but TFF2 treatment did not influence airway inflammation. The increased expression of endogenous TFF2 in response to chronic allergic inflammation is insufficient to prevent the progression of airway inflammation and remodeling in a murine model of chronic AAD. However, exogenous TFF2 treatment is effective in reversing aspects of established airway remodeling. TFF2 has potential as a novel treatment for airway remodeling in asthma.

Lipopolysaccharide hyperpolarizes guinea pig airway epithelium by increasing the activities of the epithelial Na(+) channel and the Na(+)-K(+) pump.

Science.gov (United States)

Dodrill, Michael W; Fedan, Jeffrey S

2010-10-01

Earlier, we found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (V(t)) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. As well, LPS increased the hyperpolarization component of the response to basolateral methacholine, and potentiated the epithelium-derived relaxing factor-mediated relaxation responses to hyperosmolar solutions applied to the apical membrane. We hypothesized that LPS stimulates the transepithelial movement of Na(+) via the epithelial sodium channel (ENaC)/Na(+)-K(+) pump axis, leading to hyperpolarization of V(t). LPS increased the V(t)-depolarizing response to amiloride (10 μM), i.e., offset the effect of LPS, indicating that Na(+) transport activity was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na(+)-K(+) pump with basolateral amphotericin B (7.5 μM). LPS had no effect on the hyperpolarization response to apical trypsin (100 U/ml) in the Ussing chamber, indicating that channel-activating proteases are not involved in the LPS-induced activation of ENaC. To assess Na(+)-K(+) pump activity in the IPT, ENaC was short-circuited with apical amphotericin B. The greater V(t) in the presence of amphotericin B in tracheas from LPS-treated animals compared with controls revealed that LPS increased Na(+)-K(+) pump activity. This finding was confirmed in the Ussing chamber by inhibiting the Na(+)-K(+) pump via extracellular K(+) removal, loading the epithelium with Na(+), and observing a greater hyperpolarization response to K(+) restoration. Together, the findings of this study reveal that LPS hyperpolarizes the airway epithelium by increasing the activities of ENaC and the Na(+)-K(+) pump.

Specific immune responses against airway epithelial cells in a transgenic mouse-trachea transplantation model for obliterative airway disease

NARCIS (Netherlands)

Qu, N; de Haan, A; Harmsen, MC; Kroese, FGM; de Leij, LFMH; Prop, J

2003-01-01

Background. Immune injury to airway epithelium is suggested to play a central role in the pathogenesis of obliterative bronchiolitis (OB) after clinical lung transplantation. In several studies, a rejection model of murine trachea transplants is used, resulting in obliterative airway disease (OAD)

Water permeability in human airway epithelium

DEFF Research Database (Denmark)

Pedersen, Peter Steen; Procida, Kristina; Larsen, Per Leganger

2005-01-01

Osmotic water permeability (P(f)) was studied in spheroid-shaped human airway epithelia explants derived from nasal polyps by the use of a new improved tissue collection and isolation procedure. The fluid-filled spheroids were lined with a single cell layer with the ciliated apical cell membrane ...

Levcromakalim- and isoprenaline-induced relaxation of human isolated airways--role of the epithelium and of K+ channel activation.

Science.gov (United States)

Black, J L; Johnson, P R; McKay, K O; Carey, D; Armour, C L

1994-06-01

In this study we have investigated the mechanism of action of levcromakalim and isoprenaline in human isolated airways with respect to the K+ channels they activate and the possibility that these smooth muscle relaxants activate K+ channels on the airway epithelium. Mechanical removal of the epithelial layer (mean percentage of epithelium present 20 +/- 3%, n = 20 tissues) did not affect the relaxation responses to levcromakalim or isoprenaline, either in terms of maximal relaxation or sensitivity. Whilst having no effect on isoprenaline-induced relaxation, studied from basal tone, the ATP-sensitive K+ channel blocker BRL 31660 (10, 30 and 50 microM) reduced relaxation responses induced (from basal tone) by levcromakalim from 74 +/- 6% (of the maximal response to isoprenaline) to 48 +/- 12% (n = 7), 9 +/- 9% (n = 4) and 0 (n = 4), respectively. Charybdotoxin, a blocker of high conductance Ca(2+)-activated K+ channels, at concentrations of 30 and 100 nM, had no effect on either levcromakalim- or or isoprenaline-induced relaxation responses and yet charybdotoxin was active at KCa channels in outside-out patches of hippocampal granule cells. Moreover, tetraethylammonium (10 mM) inhibited neither isoprenaline- nor levcromakalim-induced relaxation. This study has demonstrated that the relaxation responses elicited in human bronchus to isoprenaline and levcromakalim are likely to be the result of direct effects on the smooth muscle with no contribution from epithelial receptors or K+ channels. The actions of levcromakalim appear to be mediated only via activation of KATP channels. Further, we have made the important observation that, under the experimental conditions of our study, isoprenaline does not activate the KCa channel to produce relaxation in human bronchus.

EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium.

Science.gov (United States)

Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J; Roschmann, Kristina I L; Fokkens, Wytske J; van Drunen, Cornelis M

2015-05-01

Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could contribute to the activation of the inflammatory state. We silenced the expression of EGR-1 or DUSP-1 in the airway epithelial cell line NCI-H292. The cell lines were stimulated in a 24-h time course with the house dust mite allergen or poly(I:C). RNA expression profiles of cytokines were established using q-PCR and protein levels were determined in supernatants with ELISA. The shRNA-mediated gene silencing reduced expression levels of EGR-1 by 92% (p<0.0001) and of DUSP-1 by 76% (p<0.0001). Both mutant cells lines showed an increased and prolonged response to the HDM allergen. The mRNA induction of IL-6 was 4.6 fold (p=0.02) and 2.4 fold higher (p=0.01) in the EGR-1 and DUSP-1 knock-down, respectively when compared to the induced levels in the control cell line. For IL-8, the induction levels were 4.6 fold (p=0.01) and 13.0 (p=0.001) fold higher. The outcome was largely similar, yet not identical at the secreted protein levels. Furthermore, steroids were able to suppress the poly(I:C) induced cytokine levels by 70-95%. Deregulation of EGR-1 and/or DUSP-1 in nasal epithelium could be responsible for the prolonged activated transcriptional state observed in vivo in allergic disease. This could have clinical consequences as cytokine levels after the steroid treatment in EGR-1 or DUSP-1 knock-down remained higher than in the control cell line. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic modification of adeno-associated viral vector type 2 capsid enhances gene transfer efficiency in polarized human airway epithelial cells.

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White, April F; Mazur, Marina; Sorscher, Eric J; Zinn, Kurt R; Ponnazhagan, Selvarangan

2008-12-01

Cystic fibrosis (CF) is a common genetic disease characterized by defects in the expression of the CF transmembrane conductance regulator (CFTR) gene. Gene therapy offers better hope for the treatment of CF. Adeno-associated viral (AAV) vectors are capable of stable expression with low immunogenicity. Despite their potential in CF gene therapy, gene transfer efficiency by AAV is limited because of pathophysiological barriers in these patients. Although a few AAV serotypes have shown better transduction compared with the AAV2-based vectors, gene transfer efficiency in human airway epithelium has still not reached therapeutic levels. To engineer better AAV vectors for enhanced gene delivery in human airway epithelium, we developed and characterized mutant AAV vectors by genetic capsid modification, modeling the well-characterized AAV2 serotype. We genetically incorporated putative high-affinity peptide ligands to human airway epithelium on the GH loop region of AAV2 capsid protein. Six independent mutant AAV were constructed, containing peptide ligands previously reported to bind with high affinity for known and unknown receptors on human airway epithelial cells. The vectors were tested on nonairway cells and nonpolarized and polarized human airway epithelial cells for enhanced infectivity. One of the mutant vectors, with the peptide sequence THALWHT, not only showed the highest transduction in undifferentiated human airway epithelial cells but also indicated significant transduction in polarized cells. Interestingly, this modified vector was also able to infect cells independently of the heparan sulfate proteoglycan receptor. Incorporation of this ligand on other AAV serotypes, which have shown improved gene transfer efficiency in the human airway epithelium, may enhance the application of AAV vectors in CF gene therapy.

Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses

Science.gov (United States)

Jazaeri Farsani, Seyed Mohammad; Deijs, Martin; Dijkman, Ronald; Molenkamp, Richard; Jeeninga, Rienk E; Ieven, Margareta; Goossens, Herman; van der Hoek, Lia

2015-01-01

Background Currently, virus discovery is mainly based on molecular techniques. Here, we propose a method that relies on virus culturing combined with state-of-the-art sequencing techniques. The most natural ex vivo culture system was used to enable replication of respiratory viruses. Method Three respiratory clinical samples were tested on well-differentiated pseudostratified tracheobronchial human airway epithelial (HAE) cultures grown at an air–liquid interface, which resemble the airway epithelium. Cells were stained with convalescent serum of the patients to identify infected cells and apical washes were analyzed by VIDISCA-454, a next-generation sequencing virus discovery technique. Results Infected cells were observed for all three samples. Sequencing subsequently indicated that the cells were infected by either human coronavirus OC43, influenzavirus B, or influenzavirus A. The sequence reads covered a large part of the genome (52%, 82%, and 57%, respectively). Conclusion We present here a new method for virus discovery that requires a virus culture on primary cells and an antibody detection. The virus in the harvest can be used to characterize the viral genome sequence and cell tropism, but also provides progeny virus to initiate experiments to fulfill the Koch's postulates. PMID:25482367

Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.

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Vanthanouvong, V; Kozlova, I; Johannesson, M; Nääs, E; Nordvall, S L; Dragomir, A; Roomans, G M

2006-04-01

The ionic composition of the airway surface liquid (ASL) in healthy individuals and in patients with cystic fibrosis (CF) has been debated. Ion transport properties of the upper airway epithelium are similar to those of the lower airways and it is easier to collect nasal ASL from the nose. ASL was collected with ion exchange beads, and the elemental composition of nasal fluid was determined by X-ray microanalysis in healthy subjects, CF patients, CF heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD). In healthy subjects, the ionic concentrations were approximately isotonic. In CF patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were significantly higher compared when compared with those in controls. [K] was significantly higher in CF and PCD patients compared with that in controls. Severely affected CF patients had higher ionic concentrations in their nasal ASL than in patients with mild or moderate symptoms. Female CF patients had higher levels of Na, Cl, and K than male patients. As higher salt concentrations in the ASL are also found in other patients with airway diseases involving chronic inflammation, it appears likely that inflammation-induced epithelial damage is important in determining the ionic composition of the ASL. Copyright (c) 2006 Wiley-Liss, Inc.

Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

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Chen, Jichao; Krasnow, Mark A.

2012-01-01

Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program. PMID:23285215

Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells.

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Hannan, Nicholas R F; Sampaziotis, Fotios; Segeritz, Charis-Patricia; Hanley, Neil A; Vallier, Ludovic

2015-07-15

Collectively, lung diseases are one of the largest causes of premature death worldwide and represent a major focus in the field of regenerative medicine. Despite significant progress, only few stem cell platforms are currently available for cell-based therapy, disease modeling, and drug screening in the context of pulmonary disorders. Human foregut stem cells (hFSCs) represent an advantageous progenitor cell type that can be used to amplify large quantities of cells for regenerative medicine applications and can be derived from any human pluripotent stem cell line. Here, we further demonstrate the application of hFSCs by generating a near homogeneous population of early pulmonary endoderm cells coexpressing NKX2.1 and FOXP2. These progenitors are then able to form cells that are representative of distal airway epithelium that express NKX2.1, GATA6, and cystic fibrosis transmembrane conductance regulator (CFTR) and secrete SFTPC. This culture system can be applied to hFSCs carrying the CFTR mutation Δf508, enabling the development of an in vitro model for cystic fibrosis. This platform is compatible with drug screening and functional validations of small molecules, which can reverse the phenotype associated with CFTR mutation. This is the first demonstration that multipotent endoderm stem cells can differentiate not only into both liver and pancreatic cells but also into lung endoderm. Furthermore, our study establishes a new approach for the generation of functional lung cells that can be used for disease modeling as well as for drug screening and the study of lung development.

PLUNC: a multifunctional surfactant of the airways

OpenAIRE

Bartlett, Jennifer; Gakhar, Lokesh; Penterman, Jon; Singh, Pradeep; Mallampalli, Rama K.; Porter, Edith; McCray, Paul B.

2011-01-01

PLUNC (palate, lung and nasal epithelium clone) protein is an abundant secretory product of epithelia throughout the mammalian conducting airways. Despite its homology with the innate immune defence molecules BPI (bactericidal/permeability-increasing protein) and LBP (lipopolysaccharide-binding protein), it has been difficult to define the functions of PLUNC. Based on its marked hydrophobicity and expression pattern, we hypothesized that PLUNC is an airway surfactant. We found that purified r...

Exploring the context of the lung proteome within the airway mucosa following allergen challenge.

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Fehniger, Thomas E; Sato-Folatre, José-Gabriel; Malmström, Johan; Berglund, Magnus; Lindberg, Claes; Brange, Charlotte; Lindberg, Henrik; Marko-Varga, György

2004-01-01

The lung proteome is a dynamic collection of specialized proteins related to pulmonary function. Many cells of different derivations, activation states, and levels of maturity contribute to the changing environment, which produces the lung proteome. Inflammatory cells reacting to environmental challenge, for example from allergens, produce and secrete proteins which have profound effects on both resident and nonresident cells located in airways, alveoli, and the vascular tree which provides blood cells to the parenchyma alveolar bed for gas exchange. In an experimental model of allergic airway inflammation, we have compared control and allergen challenged lung compartments to determine global protein expression patterns using 2D-gel electrophoresis and subsequent spot identification by MS/MS mass spectrometry. We have then specifically isolated the epithelial mucosal layer, which lines conducting airways, from control and allergen challenged lungs, using laser capture technology and performed proteome identification on these selected cell samples. A central component of our investigations has been to contextually relate the histological features of the dynamic pulmonary environment to the changes in protein expression observed following challenge. Our results provide new information of the complexity of the submucosa/epithelium interface and the mechanisms behind the transformation of airway epithelium from normal steady states to functionally activated states.

Phenotypic and physiologic variability in nasal epithelium cultured from smokers and non-smokers exposed to secondhand tobacco smoke

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The emergence of air-liquid interface (ALI) culturing of mammalian airway epithelium is a recent innovation for experimental modeling of airway epithelial development, function, and pathogenic mechanisms associated with infectious agent and irritant exposure. This construct provi...

Expression of taste receptors in Solitary Chemosensory Cells of rodent airways

OpenAIRE

Tizzano, Marco; Cristofoletti, Mirko; Sbarbati, Andrea; Finger, Thomas E

2011-01-01

Abstract Background Chemical irritation of airway mucosa elicits a variety of reflex responses such as coughing, apnea, and laryngeal closure. Inhaled irritants can activate either chemosensitive free nerve endings, laryngeal taste buds or solitary chemosensory cells (SCCs). The SCC population lies in the nasal respiratory epithelium, vomeronasal organ, and larynx, as well as deeper in the airway. The objective of this study is to map the distribution of SCCs within the airways and to determi...

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

Inefficient cationic lipid-mediated siRNA and antisense oligonucleotide transfer to airway epithelial cells in vivo

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Hu Jim

2006-02-01

Full Text Available Abstract Background The cationic lipid Genzyme lipid (GL 67 is the current "gold-standard" for in vivo lung gene transfer. Here, we assessed, if GL67 mediated uptake of siRNAs and asODNs into airway epithelium in vivo. Methods Anti-lacZ and ENaC (epithelial sodium channel siRNA and asODN were complexed to GL67 and administered to the mouse airway epithelium in vivo Transfection efficiency and efficacy were assessed using real-time RT-PCR as well as through protein expression and functional studies. In parallel in vitro experiments were carried out to select the most efficient oligonucleotides. Results In vitro, GL67 efficiently complexed asODNs and siRNAs, and both were stable in exhaled breath condensate. Importantly, during in vitro selection of functional siRNA and asODN we noted that asODNs accumulated rapidly in the nuclei of transfected cells, whereas siRNAs remained in the cytoplasm, a pattern consistent with their presumed site of action. Following in vivo lung transfection siRNAs were only visible in alveolar macrophages, whereas asODN also transfected alveolar epithelial cells, but no significant uptake into conducting airway epithelial cells was seen. SiRNAs and asODNs targeted to β-galactosidase reduced βgal mRNA levels in the airway epithelium of K18-lacZ mice by 30% and 60%, respectively. However, this was insufficient to reduce protein expression. In an attempt to increase transfection efficiency of the airway epithelium, we increased contact time of siRNA and asODN using the in vivo mouse nose model. Although highly variable and inefficient, transfection of airway epithelium with asODN, but not siRNA, was now seen. As asODNs more effectively transfected nasal airway epithelial cells, we assessed the effect of asODN against ENaC, a potential therapeutic target in cystic fibrosis; no decrease in ENaC mRNA levels or function was detected. Conclusion This study suggests that although siRNAs and asODNs can be developed to inhibit

Human airway epithelial cell cultures for modeling respiratory syncytial virus infection.

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Pickles, Raymond J

2013-01-01

Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of how RSV causes airway disease and greatly limited the development of therapeutic strategies for reducing RSV disease burden. Our current knowledge of RSV infection and pathology is largely based on in vitro studies using nonpolarized epithelial cell-lines grown on plastic or in vivo studies using animal models semipermissive for RSV infection. Although these models have revealed important aspects of RSV infection, replication, and associated inflammatory responses, these models do not broadly recapitulate the early interactions and potential consequences of RSV infection of the human columnar airway epithelium in vivo. In this chapter, the pro et contra of in vitro models of human columnar airway epithelium and their usefulness in respiratory virus pathogenesis and vaccine development studies will be discussed. The use of such culture models to predict characteristics of RSV infection and the correlation of these findings to the human in vivo situation will likely accelerate our understanding of RSV pathogenesis potentially identifying novel strategies for limiting the severity of RSV-associated airway disease.

Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

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Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

2014-01-01

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice.

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Seys, Leen J M; Verhamme, Fien M; Dupont, Lisa L; Desauter, Elke; Duerr, Julia; Seyhan Agircan, Ayca; Conickx, Griet; Joos, Guy F; Brusselle, Guy G; Mall, Marcus A; Bracke, Ken R

2015-01-01

Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na⁺ channel (βENaC). βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.

Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

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Di Jiang

Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

Nitric Oxide Synthase Enzymes in the Airways of Mice Exposed to Ovalbumin: NOS2 Expression Is NOS3 Dependent

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Jennifer M. Bratt

2010-01-01

Full Text Available Objectives and Design. The function of the airway nitric oxide synthase (NOS isoforms and the lung cell types responsible for its production are not fully understood. We hypothesized that NO homeostasis in the airway is important to control inflammation, which requires upregulation, of NOS2 protein expression by an NOS3-dependent mechanism. Materials or Subjects. Mice from a C57BL/6 wild-type, NOS1−/−, NOS2−/−, and NOS3−/− genotypes were used. All mice strains were systemically sensitized and exposed to filtered air or ovalbumin (OVA aerosol for two weeks to create a subchronic model of allergen-induced airway inflammation. Methods. We measured lung function, lung lavage inflammatory and airway epithelial goblet cell count, exhaled NO, nitrate and nitrite concentration, and airway NOS1, NOS2, and NOS3 protein content. Results. Deletion of NOS1 or NOS3 increases NOS2 protein present in the airway epithelium and smooth muscle of air-exposed animals. Exposure to allergen significantly reduced the expression of NOS2 protein in the airway epithelium and smooth muscle of the NOS3−/− strain only. This reduction in NOS2 expression was not due to the replacement of epithelial cells with goblet cells as remaining epithelial cells did not express NOS2. NOS1−/− animals had significantly reduced goblet cell metaplasia compared to C57Bl/6 wt, NOS2−/−, and NOS3−/− allergen-exposed mice. Conclusion. The airway epithelial and smooth muscle cells maintain a stable airway NO concentration under noninflammatory conditions. This “homeostatic” mechanism is unable to distinguish between NOS derived from the different constitutive NOS isoforms. NOS3 is essential for the expression of NOS2 under inflammatory conditions, while NOS1 expression contributes to allergen-induced goblet cell metaplasia.

Nitric Oxide Synthase Enzymes in the Airways of Mice Exposed to Ovalbumin: NOS2 Expression Is NOS3 Dependent

Science.gov (United States)

Bratt, Jennifer M.; Williams, Keisha; Rabowsky, Michelle F.; Last, Michael S.; Franzi, Lisa M.; Last, Jerold A.; Kenyon, Nicholas J.

2010-01-01

Objectives and Design. The function of the airway nitric oxide synthase (NOS) isoforms and the lung cell types responsible for its production are not fully understood. We hypothesized that NO homeostasis in the airway is important to control inflammation, which requires upregulation, of NOS2 protein expression by an NOS3-dependent mechanism. Materials or Subjects. Mice from a C57BL/6 wild-type, NOS1−/−, NOS2−/−, and NOS3−/− genotypes were used. All mice strains were systemically sensitized and exposed to filtered air or ovalbumin (OVA) aerosol for two weeks to create a subchronic model of allergen-induced airway inflammation. Methods. We measured lung function, lung lavage inflammatory and airway epithelial goblet cell count, exhaled NO, nitrate and nitrite concentration, and airway NOS1, NOS2, and NOS3 protein content. Results. Deletion of NOS1 or NOS3 increases NOS2 protein present in the airway epithelium and smooth muscle of air-exposed animals. Exposure to allergen significantly reduced the expression of NOS2 protein in the airway epithelium and smooth muscle of the NOS3−/− strain only. This reduction in NOS2 expression was not due to the replacement of epithelial cells with goblet cells as remaining epithelial cells did not express NOS2. NOS1−/− animals had significantly reduced goblet cell metaplasia compared to C57Bl/6 wt, NOS2−/−, and NOS3−/− allergen-exposed mice. Conclusion. The airway epithelial and smooth muscle cells maintain a stable airway NO concentration under noninflammatory conditions. This “homeostatic” mechanism is unable to distinguish between NOS derived from the different constitutive NOS isoforms. NOS3 is essential for the expression of NOS2 under inflammatory conditions, while NOS1 expression contributes to allergen-induced goblet cell metaplasia. PMID:20953358

Selective response of human airway epithelia to luminal but not serosal solution hypertonicity. Possible role for proximal airway epithelia as an osmolality transducer

DEFF Research Database (Denmark)

Willumsen, Niels J.; Davis, C.W.; Boucher, R.C.

1994-01-01

exposure (10 min) to 430 mosM luminal solution elicited no regulation of any parameter. Optical measurements revealed a reduction in the thickness of preparations only in response to luminal hypertonic solutions. We conclude that (a) airway epithelial cells exhibit asymmetric water transport properties......- secretion; and (d) cell volume loss increases the resistance of the paracellular path. We speculate that these properties configure human nasal epithelium to behave as an osmotic sensor, transducing information about luminal solutions to the airway wall....

Alcohol and airways function in health and disease.

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Sisson, Joseph H

2007-08-01

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The effect of alcohol on lung airway functions is dependent on the concentration, duration, and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation, and probably attenuates the airway inflammation and injury observed in asthma and chronic obstructive pulmonary disease (COPD). Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management, and likely worsens outcomes including lung function and mortality in COPD patients. Nonalcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol- and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase 2. The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation, and the interaction with other airway exposure agents, such as cigarette smoke, represents opportunities for future investigation.

Comparison of Effect of Hypoxia on Epithelium of Trachea and Terminal Bronchioles

Czech Academy of Sciences Publication Activity Database

Uhlík, J.; Konrádová, V.; Vajner, L.; Adášková, Jana; Herget, J.

2003-01-01

Roč. 9, Suppl. 3 (2003), s. 478-479 ISSN 1431-9276. [Microscopy Conference /31./. Dresden, 07.09.2003-12.09.2003] Source of funding: V - iné verejné zdroje Keywords : airway epithelium * Clara cells * ciliated cells * hypoxia * electron microscopy Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.648, year: 2003

A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium

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Sparrow Malcolm P

2005-10-01

Full Text Available Abstract Background Pulmonary neuroendocrine cells (PNEC are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Methods Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1 undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5, sensory nerves (calcitonin gene related peptide, CGRP, and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP. The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. Results PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Conclusion Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

Metachronal waves in epithelium cilia to transport bronchial mucus in airways

Science.gov (United States)

Favier, Julien; Sylvain, Chateau; D'Ortona, Umberto; Poncet, Sébastien

2017-11-01

Metachronal waves of beating cilia are an efficient mechanism to transport mucus in human airways. The numerical results we will present will shed new light on the understanding of chronic respiratory diseases, such as Asthma of COPD. A coupled lattice Boltzmann - Immersed Boundary is used to simulate the multiphase environment in which the cilia are immersed: a periciliary layer and the mucus layer. A purely hydrodynamical feedback of the fluids is taken into account, and a coupling parameter α is introduced, allowing the tuning of both the direction of the wave propagation, and the strength of the fluid feedback. The cilia, initially set in a random state, quickly synchronize with their immediate neighbors giving birth to metachronal waves. A comparative study of both antipleptic and sympleptic waves is performed by imposing the metachrony. Antiplectic waves are found to be the most efficient to transport and mix fluids compared to other random or synchronised cilia motions. The numerical results will be discussed and compared to experimental and clinical results obtained by collaborators, to progress on the understanding of the inner mechanisms of chronic respiratory diseases.

Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats.

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Yunye Ning

Full Text Available BACKGROUND: Over-production of mucus is an important pathophysiological feature in chronic airway disease such as chronic obstructive pulmonary disease (COPD and asthma. Cigarette smoking (CS is the leading cause of COPD. Oxidative stress plays a key role in CS-induced airway abnormal mucus production. Hydrogen protected cells and tissues against oxidative damage by scavenging hydroxyl radicals. In the present study we investigated the effect of hydrogen on CS-induced mucus production in rats. METHODS: Male Sprague-Dawley rats were divided into four groups: sham control, CS group, hydrogen-rich saline pretreatment group and hydrogen-rich saline control group. Lung morphology and tissue biochemical changes were determined by immunohistochemistry, Alcian Blue/periodic acid-Schiff staining, TUNEL, western blot and realtime RT-PCR. RESULTS: Hydrogen-rich saline pretreatment attenuated CS-induced mucus accumulation in the bronchiolar lumen, goblet cell hyperplasia, muc5ac over-expression and abnormal cell apoptosis in the airway epithelium as well as malondialdehyde increase in the BALF. The phosphorylation of EGFR at Tyr1068 and Nrf2 up-regulation expression in the rat lungs challenged by CS exposure were also abrogated by hydrogen-rich saline. CONCLUSION: Hydrogen-rich saline pretreatment ameliorated CS-induced airway mucus production and airway epithelium damage in rats. The protective role of hydrogen on CS-exposed rat lungs was achieved at least partly by its free radical scavenging ability. This is the first report to demonstrate that intraperitoneal administration of hydrogen-rich saline protected rat airways against CS damage and it could be promising in treating abnormal airway mucus production in COPD.

Effects of nitrous oxide on the production of cytokines and chemokines by the airway epithelium during anesthesia with sevoflurane and propofol.

Science.gov (United States)

Kumakura, Seiichiro; Yamaguchi, Keisuke; Sugasawa, Yusuke; Murakami, Taisuke; Kikuchi, Toshihiro; Inada, Eiichi; Nagaoka, Isao

2013-12-01

The aim of this study was to evaluate the effects of nitrous oxide (a gaseous anesthetic) on the in vivo production of inflammatory cytokines and chemokines by the airway epithelium, when combined with sevoflurane or propofol. Subjects undergoing simple or segmental mastectomy were randomly assigned to the sevoflurane and nitrous oxide, sevoflurane and air, propofol and nitrous oxide, or propofol and air group (all n=13). Epithelial lining fluid (ELF) was obtained using the bronchoscopic microsampling method prior to and following the mastectomy to enable measurement of the pre- and post-operative levels of certain inflammatory cytokines and chemokines using a cytometric bead array system. Notably, the levels of interleukin (IL)-1β, IL-8 and monocyte chemotactic protein-1 (MCP-1) in the ELF were significantly increased following the operations which involved the inhalation of sevoflurane and nitrous oxide, although the levels of these molecules were not significantly changed by the inhalation of sevoflurane and air. Furthermore, the IL-12p70 levels were significantly reduced in the ELF following the operations that involved the inhalation of sevoflurane and air, although the IL-12p70 levels were not significantly changed by the inhalation of nitrous oxide and sevoflurane. These observations suggest that the combination of sevoflurane and nitrous oxide induces an inflammatory response (increased production of IL-1β, IL-8 and MCP-1) and suppresses the anti-inflammatory response (reduced production of IL-12p70) in the local milieu of the airway. Thus, the combination of these compounds should be carefully administered for anesthesia.

High degree of overlap between responses to a virus and to the house dust mite allergen in airway epithelial cells

NARCIS (Netherlands)

Golebski, Korneliusz; Luiten, Silvia; van Egmond, Danielle; de Groot, Esther; Röschmann, Kristina Irene Lisolette; Fokkens, Wytske Johanna; van Drunen, Cornelis Maria

2014-01-01

Airway epithelium is widely considered to play an active role in immune responses through its ability to detect changes in the environment and to generate a microenvironment for immune competent cells. Therefore, besides its role as a physical barrier, epithelium affects the outcome of the immune

Airway hyperresponsiveness; smooth muscle as the principal actor [version 1; referees: 2 approved

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Anne-Marie Lauzon

2016-03-01

Full Text Available Airway hyperresponsiveness (AHR is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-α promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway.

A prospective study to evaluate and compare laryngeal mask airway ProSeal and i-gel airway in the prone position.

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Taxak, Susheela; Gopinath, Ajith; Saini, Savita; Bansal, Teena; Ahlawat, Mangal Singh; Bala, Manju

2015-01-01

Prone position is commonly used to provide surgical access to a variety of surgeries. In view of the advantages of induction of anesthesia in the prone position, we conducted a randomized study to evaluate and compare ProSeal laryngeal mask airway (LMA) and i-gel in the prone position. Totally, 40 patients of either sex as per American Society of Anesthesiologists physical status I or II, between 16 and 60 years of age, scheduled to undergo surgery in prone position were included in the study. After the patients positioned themselves prone on the operating table, anesthesia was induced by the standard technique. LMA ProSeal was used as an airway conduit in group 1 while i-gel was used in group 2. At the end of surgery, the airway device was removed in the same position. Insertion of airway device was successful in first attempt in 16, and 17 cases in ProSeal laryngeal mask airway (PLMA) and i-gel groups, respectively. A second attempt was required to secure the airway in 4 and 3 patients in PLMA and i-gel groups, respectively. The mean insertion time was 21.8 ± 2.70 s for group 1 and 13.1 ± 2.24 s for group 2, the difference being statistically significant (P position. The PLMA has a better seal while insertion is easier with i-gel.

Morphological findings in the tracheal epithelium of dogs exposed to the inhalation of poorly conditioned gases under use of an endotracheal tube or laryngeal mask airway.

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Dias, Norimar Hernandes; Braz, José Reinaldo Cerqueira; Defaveri, Júlio; Carvalho, Lídia Raquel; Martins, Regina Helena Garcia

2011-10-01

To study morphological findings in the tracheal epithelium of dogs exposed to the inhalation of poorly conditioned gases under use of an endotracheal tube (ET) or laryngeal mask airway (LMA). Twelve dogs randomly were allocated to two groups: ET group (n-6) and LMA group (n-6), anaesthetized and mechanically ventilated, without CO(2) reabsorption. Haemodynamic and ventilatory parameters, tympanic temperature, temperature, relative and absolute humidity of the ambient and inhaled gases were analyzed during three hours. The animals were submitted to euthanasia and biopsies were carried out along the tracheal segment to morphological study. Three healthy dogs were used to morphological control. Inhaled gas temperature was maintained between 24ºC and 26ºC, relative humidity between 10% and 12%, and absolute humidity between 2 - 3 mg H(2)O.L(-1) with no significant differences between groups. In both groups, histological analysis showed epithelial inflammation and congestion in the corion and scanning electron microscopy showed ciliary grouping and disorganization. Transmission electron microscopy showed higher alterations in ET group than LMA group as widening of cell junctions, ciliary disorientation, cytoplasmic vacuolization, nuclear abnormalities, picnosis and chromatin condensation. LMA determined less pronounced changes in the tracheal epithelium in dogs exposed to the inhalation of poorly conditioned gases.

Bacillus licheniformis in geogenic dust induces inflammation in respiratory epithelium.

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Pickering, Janessa; Teo, Teck Hui; Thornton, Ruth B; Kirkham, Lea-Ann; Zosky, Graeme R; Clifford, Holly D

2018-07-01

Exposure to environmental geogenic (or earth-derived) dust can lead to more frequent and severe infections in the human airway. Particulate matter respiratory diseases. We have previously demonstrated that mice exposed to geogenic dust PM 10 experienced an exacerbation of inflammatory responses to influenza A virus. Whether geogenic dust PM 10 also exacerbates respiratory bacterial infection is not yet known, nor are the components of the dust that drive these responses. We treated airway bronchial epithelial cells (NuLi-1) with UV-irradiated geogenic dust PM 10 from six remote Western Australian towns. High levels of IL-6 and IL-8 production were observed, as well as persistent microbial growth. 16 S rRNA sequencing of the growth identified the microbe as Bacillus licheniformis, a spore-forming, environmentally abundant bacterium. We next investigated the interaction of B. licheniformis with respiratory epithelium in vitro to determine whether this exacerbated infection with a bacterial respiratory pathogen (non-typeable Haemophilus influenzae, NTHi). Heat treatment (100 °C) of all PM 10 samples eliminated B. licheniformis contamination and reduced epithelial inflammatory responses, suggesting that heat-labile and/or microbial factors were involved in the host response to geogenic dust PM 10 . We then exposed NuLi-1 epithelium to increasing doses of the isolated Bacillus licheniformis (multiplicity of infection of 10:1, 1:1 or 0.1:1 bacteria: cells) for 1, 3, and 24 h. B. licheniformis and NTHi infection (association and invasion) was assessed using a standard gentamicin survival assay, and epithelial release of IL-6 and IL-8 was measured using a bead based immunoassay. B. licheniformis was cytotoxic to NuLi-1 cells at 24 h. At 3 h post-challenge, B. licheniformis elicited high IL-6 and IL-8 inflammatory responses from NuLi-1 cells compared with cells treated with heat-treated geogenic dust PM 10 (p respiratory epithelium. The impact on respiratory

Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

Energy Technology Data Exchange (ETDEWEB)

Rodgers, D.A.; Nikula, K.J.; Avila, K. [and others

1995-12-01

The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models to human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.

The effect of long-term administered CRAC channels blocker on the functions of respiratory epithelium in guinea pig allergic asthma model.

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Sutovska, Martina; Kocmalova, Michaela; Joskova, Marta; Adamkov, Marian; Franova, Sona

2015-04-01

Previously, therapeutic potency of CRAC channels blocker was evidenced as a significant decrease in airway smooth muscle hyperreactivity, antitussive and anti-inflammatory effects. The major role of the respiratory epithelium in asthma pathogenesis was highlighted only recently and CRAC channels were proposed as the most significant route of Ca2+ entry into epithelial cells. The aim of the study was to analyse the impact of long-term administered CRAC channels blocker on airway epithelium, e.g. cytokine production and ciliary beat frequency (CBF) using an animal model of allergic asthma. Ovalbumin-induced allergic airway inflammation of guinea pigs was followed by long-term (14 days lasted) therapy by CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA). The influence of long-term therapy on cytokines (IL-4, IL-5 and IL-13) in BALF and in plasma, immunohistochemical staining of pulmonary tissue (c-Fos positivity) and CBF in vitro were used for analysis. Decrease in cytokine levels and in c-Fos positivity confirmed an anti-inflammatory effect of long-term administered FPCA. Cytokine levels in BALF and distribution of c-Fos positivity suggested that FPCA was a more potent inhibitor of respiratory epithelium secretory functions than budesonide. FPCA and budesonide reduced CBF only insignificantly. All findings supported CRAC channels as promising target in the new strategy of antiasthmatic treatment.

Lipopolysaccharide increases Na(+),K(+)-pump, but not ENaC, expression in guinea-pig airway epithelium.

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Dodrill, Michael W; Beezhold, Donald H; Meighan, Terence; Kashon, Michael L; Fedan, Jeffrey S

2011-01-25

Earlier, we found in functional experiments that lipopolysaccharide (LPS; 4mg/kg; i.p.) hyperpolarized the epithelium by stimulating the transepithelial transport of Na(+) in guinea-pig tracheal epithelium. Epithelial sodium channel (ENaC) activity and Na(+),K(+)-pump activity were increased. In this study, we hypothesized that LPS increases the expression of ENaC and the Na(+),K(+)-pump in the epithelium and investigated the levels of transcription and protein abundance. Using qPCR, the effects of LPS on the transcription of αENaC, α(1) Na(+),K(+)-pump, COX-2, eNOS, iNOS, IL-1β, and TNF-α were measured at 3 and 18h. In the epithelium, LPS increased the transcription of COX-2, IL-1β, and, to a nonsignificant extent, TNF-α at 3h, but not at 18h. In alveolar macrophages, TNF-α, and, to a nonsignificant extent, COX-2 and IL-1β were up-regulated at 3h, but not at 18h. Even though LPS stimulated the transcription of some genes, αENaC and α(1) Na(+),K(+)-ATPase transcription were not affected. The expressions of α-, β-, and γ-ENaC and α(1) Na(+),K(+)-pump from the tracheal epithelium and kidney cortex/medulla were investigated by western blotting. All three ENaC subunits were detected as cleavage fragments, yet LPS had no effect on their expression. LPS increased the expression of the α(1) subunit and the α(1), α(2), and α(3) subunits, collectively, of the Na(+),K(+)-pump. Taken together, these data indicate that LPS increases Na(+) transport downstream of the genetic level, in part, by stimulating the expression of the Na(+),K(+)-pump. Published by Elsevier B.V.

Manipulation of Cell Physiology Enables Gene Silencing in Well-differentiated Airway Epithelia

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Sateesh Krishnamurthy

2012-01-01

Full Text Available The application of RNA interference-based gene silencing to the airway surface epithelium holds great promise to manipulate host and pathogen gene expression for therapeutic purposes. However, well-differentiated airway epithelia display significant barriers to double-stranded small-interfering RNA (siRNA delivery despite testing varied classes of nonviral reagents. In well-differentiated primary pig airway epithelia (PAE or human airway epithelia (HAE grown at the air–liquid interface (ALI, the delivery of a Dicer-substrate small-interfering RNA (DsiRNA duplex against hypoxanthine–guanine phosphoribosyltransferase (HPRT with several nonviral reagents showed minimal uptake and no knockdown of the target. In contrast, poorly differentiated cells (2–5-day post-seeding exhibited significant oligonucleotide internalization and target knockdown. This finding suggested that during differentiation, the barrier properties of the epithelium are modified to an extent that impedes oligonucleotide uptake. We used two methods to overcome this inefficiency. First, we tested the impact of epidermal growth factor (EGF, a known enhancer of macropinocytosis. Treatment of the cells with EGF improved oligonucleotide uptake resulting in significant but modest levels of target knockdown. Secondly, we used the connectivity map (Cmap database to correlate gene expression changes during small molecule treatments on various cells types with genes that change upon mucociliary differentiation. Several different drug classes were identified from this correlative assessment. Well-differentiated epithelia treated with DsiRNAs and LY294002, a PI3K inhibitor, significantly improved gene silencing and concomitantly reduced target protein levels. These novel findings reveal that well-differentiated airway epithelia, normally resistant to siRNA delivery, can be pretreated with small molecules to improve uptake of synthetic oligonucleotide and RNA interference (RNAi responses.

An ovine tracheal explant culture model for allergic airway inflammation

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Abeynaike Latasha

2010-08-01

Full Text Available Abstract Background The airway epithelium is thought to play an important role in the pathogenesis of asthmatic disease. However, much of our understanding of airway epithelial cell function in asthma has been derived from in vitro studies that may not accurately reflect the interactive cellular and molecular pathways active between different tissue constituents in vivo. Methods Using a sheep model of allergic asthma, tracheal explants from normal sheep and allergic sheep exposed to house dust mite (HDM allergen were established to investigate airway mucosal responses ex vivo. Explants were cultured for up to 48 h and tissues were stained to identify apoptotic cells, goblet cells, mast cells and eosinophils. The release of cytokines (IL-1α, IL-6 and TNF-α by cultured tracheal explants, was assessed by ELISA. Results The general morphology and epithelial structure of the tracheal explants was well maintained in culture although evidence of advanced apoptosis within the mucosal layer was noted after culture for 48 h. The number of alcian blue/PAS positive mucus-secreting cells within the epithelial layer was reduced in all cultured explants compared with pre-cultured (0 h explants, but the loss of staining was most evident in allergic tissues. Mast cell and eosinophil numbers were elevated in the allergic tracheal tissues compared to naïve controls, and in the allergic tissues there was a significant decline in mast cells after 24 h culture in the presence or absence of HDM allergen. IL-6 was released by allergic tracheal explants in culture but was undetected in cultured control explants. Conclusions Sheep tracheal explants maintain characteristics of the airway mucosa that may not be replicated when studying isolated cell populations in vitro. There were key differences identified in explants from allergic compared to control airways and in their responses in culture for 24 h. Importantly, this study establishes the potential for the

Experimental absorbable stent permits airway remodeling.

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Liu, Kuo-Sheng; Liu, Yun-Hen; Peng, Yi-Jie; Liu, Shih-Jung

2011-02-01

Despite metallic and silicone stents being effective in treating various airway lesions, many concerns still remain. A bioresorbable stent that scaffolds the airway lumen and dissolves after the remodeling process is completed has advantages over metallic and silicone stents. We designed and fabricated a new mesh-type bioresorbable stent with a backbone of polycaprolactone (PCL), and evaluated its safety and biocompatibility in a rabbit trachea model. The PCL stent was fabricated by a laboratory-made microinjection molding machine. In vitro mechanical strength of the PCL stents was tested and compared to that of commercial silicone stents. The bioresorbable stents were surgically implanted into the cervical trachea of New Zealand white rabbits (n=6). Animals received bronchoscopic examination at 1, 2, 4, 8, and 12 weeks after surgery. Histological examination was completed to evaluate the biocompatibility of the stents. No animals died during the period of study. Distal stent migration was noted in 1 rabbit. In-stent secretion accumulation was found in 2 rabbits. Histological examination showed intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area at 10 and 28 weeks. Stent degradation was minimal, and the mechanical strength was well preserved at the end of 33 weeks. These preliminary findings showed good safety and biocompatibility of the new PCL stent when used in the airway remodeling. PCL could be a promising bioresorbable material for stent design if prolonged degradation time is required. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood.

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Maria J Gutierrez

Full Text Available Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome and examine the changes during rhinovirus (RV infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.Nasal airway secretions were obtained from children (≤3 yrs. old during PCR-confirmed RV infections (n = 10 and age-matched controls (n = 10. Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our in vivo airway secretory miR data in an in vitro airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC differentiated at air-liquid interface (ALI. Bioinformatics tools were used to determine the unified (nasal and bronchial signature airway secretory miRNAome and changes during RV infection in children.Multiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: hsa-miR-630, hsa-miR-302d-3p, hsa- miR-320e, hsa-miR-612. We identified hsa-miR-155 as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of hsa-mir-155 using in silico models derived from gene datasets of experimental in vivo human RV infection. These analyses confirmed that hsa-miR-155 targetome is an overrepresented pathway in the upper airways of individuals infected with RV.Comparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway

Airway inflammation in chronic obstructive pulmonary disease (COPD): a true paradox.

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Eapen, Mathew Suji; Myers, Stephen; Walters, Eugene Haydn; Sohal, Sukhwinder Singh

2017-10-01

Chronic obstructive pulmonary disease (COPD) is primarily an airway condition, which mainly affects cigarette smokers and presents with shortness of breath that is progressive and poorly reversible. In COPD research, there has been a long held belief that airway disease progression is due to inflammation. Although this may be true in the airway lumen with innate immunity activated by the effect of smoke or secondary to infection, the accurate picture of inflammatory cells in the airway wall, where the pathophysiological COPD remodeling occurs, is uncertain and debatable. Areas covered: The current review provides a comprehensive literature survey of the changes in the main inflammatory cells in human COPD patients and focuses on contrarian views that affect the prevailing dogma on inflammation. The review also delves into the role of oxidative stress and inflammasomes in modulating the immune response in COPD. Further, the effects of inflammation in affecting the epithelium, fibroblasts, and airway remodeling are discussed. Expert commentary: Inflammation as a driving force for airway wall damage and remodelling in early COPD is at the very least 'oversimplified' and is likely to be misleading. This has serious implications for rational thinking about the illness, including pathogenesis and designing therapy.

Serelaxin Elicits Bronchodilation and Enhances β-Adrenoceptor-mediated Airway Relaxation

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Maggie Lam

2016-10-01

Full Text Available Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250-350g and tricolor guinea pigs, and precision cut lung slices (PCLS containing intrapulmonary airways were prepared from rats only. Recombinant human serelaxin (rhRLX alone and in combination with rosiglitazone (PPARγ agonist; recently described as a novel dilator or β-adrenoceptor agonists (isoprenaline, salbutamol were added either to pre-contracted airways, or before contraction with methacholine or endothelin-1. Regulation of rhRLX responses by epithelial removal, indomethacin (cyclooxygenase inhibitor, L-NAME (nitric oxide synthase inhibitor, SQ22536 (adenylate cyclase inhibitor and ODQ (guanylate cyclase inhibitor were also evaluated. Immunohistochemistry was used to localize RXFP1 to airway epithelium and smooth muscle. rhRLX elicited relaxation in rat trachea and PCLS, more slowly than rosiglitazone or isoprenaline, but potentiated relaxation to both these dilators. It markedly increased β-adrenoceptor agonist potency in guinea pig trachea. rhRLX, rosiglitazone and isoprenaline pretreatment also inhibited the development of rat tracheal contraction. Bronchoprotection by rhRLX increased with longer pre-incubation time, and was partially reduced by epithelial removal, indomethacin and/or L-NAME. SQ22536 and ODQ also partially inhibited rhRLX-mediated relaxation in both intact and epithelial-denuded trachea. RXFP1 expression in airway was at higher levels in epithelium than smooth muscle.In summary, rhRLX elicits large and small airway relaxation via epithelial-dependent and -independent mechanisms, likely

Polymeric nanocarriers for transport modulation across the pulmonary epithelium: dendrimers, polymeric nanoparticles, and their nanoblends.

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Bharatwaj, Balaji; Dimovski, Radovan; Conti, Denise S; da Rocha, Sandro R P

2014-05-01

The purpose of this study was to (a) Determine the cellular transport and uptake of amine-terminated generation 3 (G3) poly(amido amine) (PAMAM) dendrimers across an in vitro model of the pulmonary epithelium, and the ability to modulate their transport by forming nanoblends of the dendrimers with biodegradable solid polymeric nanoparticles (NPs) and (b) to formulate dendrimer nanocarriers in portable oral inhalation devices and evaluate their aerosol characteristics. To that end, fluorescein isothiocyanate (FITC)-labeled G3 PAMAM dendrimer nanocarriers (DNCs) were synthesized, and also encapsulated within poly lactide-co-glycolide nanoparticles (NPs). Transport and uptake of both DNCs encapsulated within NPs (nanoblends) and unencapsulated DNCs were tracked across polarized monolayers of airway epithelial cells, Calu-3. DNCs were also formulated as core-shell microparticles in pressurized metered-dose inhalers (pMDIs) and their aerodynamic properties evaluated by Andersen cascade impaction. The apparent permeability of DNCs across the airway epithelial model was similar to that of a paracellular marker of comparable molar mass--order of 10(-7) cm s(-1). The transport and cellular internalization of the DNCs can be modulated by formulating them as nanoblends. The transport of the DNCs across the lung epithelium was completely suppressed within the time of the experiment (5 h) when formulated as blends. The encapsulation also prevents saturation of the cellular internalization profile. Nanoblending may be a potential strategy to modulate the rate of transport and cellular uptake of DNCs, and thus be used as a design strategy to achieve enhanced local or systemic drug delivery.

Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways.

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Jill R Johnson

Full Text Available Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1 levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease.

Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

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Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2017-06-01

Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

The effects of human serum to the morphology, proliferation and gene expression level of the respiratory epithelium in vitro.

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Yunus, Mohd Heikal Mohd; Siang, Kan Chan; Hashim, Nurul Izzati; Zhi, Ng Pei; Zamani, Nur Fathurah; Sabri, Primuharsa Putra; Busra, Mohd Fauzi; Chowdhury, Shiplu Roy; Idrus, Ruszymah Binti Haji

2014-08-01

The culture of human airway epithelial cells has played an important role in advancing our understanding of the metabolic and molecular mechanisms underlying normal function and disease pathology of airway epithelial cells. The present study focused on investigating the effects of human serum (HS) on the qualitative and quantitative properties of the human respiratory epithelium compared to the fetal bovine serum (FBS), as a supplement in culture. Respiratory epithelial (RE) cells derived from human nasal turbinate were co-cultured with fibroblasts, subsequently separated at 80-90% confluency by differential trypsinization. RE cells were then sub-cultured into 2 different plates containing 5% allogenic HS and FBS supplemented media respectively up to passage 1 (P1). Cell morphology, growth rate, cell viability and population doubling time were assessed under light microscope, and levels of gene expression were measured via real time reverse transcriptase-polymerase chain reaction (qRT-PCR). RE cells appeared as polygonal shape and expanded when cultured in HS whereas RE cells in FBS were observed to be easily matured thus limit the RE cells expansion. Proliferation rate of RE cells in HS supplemented media (7673.18 ± 1207.15) was 3 times higher compared to RE in FBS supplemented media (2357.68 ± 186.85). Furthermore, RE cells cultured in HS-supplemented media required fewer days (9.15 ± 1.10) to double in numbers compared to cells cultured in FBS-supplemented media (13.66 ± 0.81). Both the differences were significant (p0.05). In conclusion, HS is a comparatively better choice of media supplement in accelerating growth kinetics of RE cells in vitro thus producing a better quality of respiratory epithelium for future tracheal reconstruction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of vectorial ion transport in primary murine airway and human sinonasal air-liquid interface cultures, models for studies of cystic fibrosis, and other airway diseases.

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Zhang, Shaoyan; Fortenberry, James A; Cohen, Noam A; Sorscher, Eric J; Woodworth, Bradford A

2009-01-01

The purpose of this study was to compare vectorial ion transport within murine trachea, murine nasal septa, and human sinonasal cultured epithelium. Our hypothesis is that murine septal epithelium, rather than trachea, will more closely mimic the electrophysiology properties of human sinonasal epithelium. Epithelium from murine trachea, murine septa, and human sinonasal tissue were cultured at an air-liquid interface to confluence and full differentiation. A limited number of homozygous dF508 epithelia were also cultured. Monolayers were mounted in modified Ussing chambers to investigate pharmacologic manipulation of ion transport. The change in forskolin-stimulated current (delta-I(SC), expressed as micro-A/cm(2)) in murine septal (n = 19; 16.84 +/- 2.09) and human sinonasal (n = 18; 12.15 +/- 1.93) cultures was significantly increased over murine tracheal cultures (n = 15; 6.75 +/- 1.35; p = 0.035 and 0.0005, respectively). Forskolin-stimulated I(SC) was inhibited by the specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5 microM). No forskolin-stimulated I(SC) was shown in cultures of dF508 homozygous murine septal epithelium (n = 3). Murine septal I(SC) was largely inhibited by amiloride (12.03 +/- 0.66), whereas human sinonasal cultures had a very limited response (0.70 +/- 0.47; p < 0.0001). The contribution of CFTR to stimulated chloride current as measured by INH-172 was highly significantly different between all groups (murine septa, 19.51 +/- 1.28; human sinonasal, 11.12 +/- 1.58; murine trachea, 4.85 +/- 0.49; p < 0.0001). Human sinonasal and murine septal epithelial cultures represent a useful model for studying CFTR activity and may provide significant advantages over lower airway tissues for investigating upper and lower respiratory pathophysiology.

Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

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Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

2015-12-01

Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway. Copyright © 2015 by Daedalus Enterprises.

Eosinophilic airway inflammation in asthmatic patients is associated with an altered airway microbiome

DEFF Research Database (Denmark)

Sverrild, Asger; Kiilerich, Pia; Brejnrod, Asker Daniel

2017-01-01

BACKGROUND: Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti......-inflammatory treatment. OBJECTIVE: We sought to describe the relationship between the airway microbiome and patterns of airway inflammation in steroid-free patients with asthma and healthy control subjects. METHODS: Bronchoalveolar lavage fluid was collected from 23 steroid-free nonsmoking patients with asthma and 10...... and AHR to mannitol but not airway neutrophilia. The overall composition of the airway microbiome of asthmatic patients with the lowest levels of eosinophils but not asthmatic patients with the highest levels of eosinophils deviated significantly from that of healthy subjects. Asthmatic patients...

Raising awareness of upper airway diseases: Overview of management and prevention strategies

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De-yun WANG

2017-11-01

Full Text Available The nose together with the paranasal sinuses is the main part of the upper airway, which is lined with pseudostratified columnar ciliated epithelium. There are several important physiological functions such as conditioning and filtration of the inspired air and the provision of end organ for the sense of smell. Besides the nose also fulfills a physical and immunological barrier as the nasal epithelium is the first site of interaction between the host tissue and foreign invaders, such as viruses, bacteria, fungi, allergens, and harmful particulates. Hence, nasal diseases such as rhinitis (allergic and infectious and rhinosinusitis are the most common health problems worldwide, affecting millions of people of all ages. In the past 10 to 20 years, our understanding of the immuno-pathophysiological mechanisms underlying the common nasal diseases has been significantly enhanced by in vivo and in vitro studies. This allows the development of novel therapeutic strategies designed to improve the physiological and immune defense functions of the nose, as well as for other common airway diseases. Since the dynamically external changes of atmosphere, environment (pollution and susceptible population, we are now facing some of new features on epidemiology and the types of upper airway diseases that require us to in-deep study the diseases through basic and clinical researches, so as to further understand the prevention, diagnosis and treatment of the diseases. DOI: 10.118555/j.issn.0577-7402.2017.10.01

Degrees of reality: airway anatomy of high-fidelity human patient simulators and airway trainers.

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Schebesta, Karl; Hüpfl, Michael; Rössler, Bernhard; Ringl, Helmut; Müller, Michael P; Kimberger, Oliver

2012-06-01

Human patient simulators and airway training manikins are widely used to train airway management skills to medical professionals. Furthermore, these patient simulators are employed as standardized "patients" to evaluate airway devices. However, little is known about how realistic these patient simulators and airway-training manikins really are. This trial aimed to evaluate the upper airway anatomy of four high-fidelity patient simulators and two airway trainers in comparison with actual patients by means of radiographic measurements. The volume of the pharyngeal airspace was the primary outcome parameter. Computed tomography scans of 20 adult trauma patients without head or neck injuries were compared with computed tomography scans of four high-fidelity patient simulators and two airway trainers. By using 14 predefined distances, two cross-sectional areas and three volume parameters of the upper airway, the manikins' similarity to a human patient was assessed. The pharyngeal airspace of all manikins differed significantly from the patients' pharyngeal airspace. The HPS Human Patient Simulator (METI®, Sarasota, FL) was the most realistic high-fidelity patient simulator (6/19 [32%] of all parameters were within the 95% CI of human airway measurements). The airway anatomy of four high-fidelity patient simulators and two airway trainers does not reflect the upper airway anatomy of actual patients. This finding may impact airway training and confound comparative airway device studies.

Comparative quantitative studies on the radiosensitivity of the oral cavity epithelium

International Nuclear Information System (INIS)

Lyubenov, T.

1986-01-01

A series of 146 patients with miscellaneous localizations of malignant tumors in the head and neck area, in whom different portions of the oral cavity epithelium came within the field subject to irradiation were included in the study. Using the Kirk's formula for cumulative radiation effect, quantitative relationships in the manifestation of radioepithelitis were searched for. With increasing the intervals of the cumulative radiation effect, the number of patients and the number of interruptions in treatment with different localizations of the tumor depended on epithelium radiosensitivity

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

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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.

Histone deacetylase inhibitors up-regulate LL-37 expression independent of toll-like receptor mediated signalling in airway epithelial cells

OpenAIRE

Liu, Q.; Liu, J.; Roschmann, K.I.L.; Egmond, D. van; Golebski, K.; Fokkens, W.J.; Wang, D.; Drunen, C.M. van

2013-01-01

HDAC inhibitors have been proposed as anticancer agents. However, their roles in innate genes expression remain not well known. Cathelicidin LL-37 is one of the few human bactericidal peptides, but the regulation of histone acetylation on LL-37 expression in airway epithelium remains largely unknown. Therefore, we investigated the effects of two non-selective HDACi, trichostatin A (TSA) and sodium butyrate (SB), on the expression of the cathelicidin LL-37 in human airway epithelial cells. LL3...

Atopic asthmatic immune phenotypes associated with airway microbiota and airway obstruction.

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Benjamin A Turturice

Full Text Available Differences in asthma severity may be related to inflammation in the airways. The lower airway microbiota has been associated with clinical features such as airway obstruction, symptom control, and response to corticosteroids.To assess the relationship between local airway inflammation, severity of disease, and the lower airway microbiota in atopic asthmatics.A cohort of young adult, atopic asthmatics with intermittent or mild/moderate persistent symptoms (n = 13 were assessed via bronchoscopy, lavage, and spirometry. These individuals were compared to age matched non-asthmatic controls (n = 6 and to themselves after six weeks of treatment with fluticasone propionate (FP. Inflammation of the airways was assessed via a cytokine and chemokine panel. Lower airway microbiota composition was determined by metagenomic shotgun sequencing.Unsupervised clustering of cytokines and chemokines prior to treatment with FP identified two asthmatic phenotypes (AP, termed AP1 and AP2, with distinct bronchoalveolar lavage inflammatory profiles. AP2 was associated with more obstruction, compared to AP1. After treatment with FP reduced MIP-1β and TNF-α and increased IL-2 was observed. A module of highly correlated cytokines that include MIP-1β and TNF-α was identified that negatively correlated with pulmonary function. Independently, IL-2 was positively correlated with pulmonary function. The airway microbiome composition correlated with asthmatic phenotypes. AP2, prior to FP treatment, was enriched with Streptococcus pneumoniae. Unique associations between IL-2 or the cytokine module and the microbiota composition of the airways were observed in asthmatics subjects prior to treatment but not after or in controls.The underlying inflammation in atopic asthma is related to the composition of microbiota and is associated with severity of airway obstruction. Treatment with inhaled corticosteroids was associated with changes in the airway inflammatory response to

Epithelium

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The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Kierszenbaum AL, Tres LL. Epithelium. In: Kierszenbaum AL, Tres LL, ... to Pathology . 4th ed. Philadelphia, PA: Elsevier Saunders; ...

Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

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Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

2015-01-01

ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

Receptor for advanced glycation end products and its ligand high-mobility group box-1 mediate allergic airway sensitization and airway inflammation.

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Ullah, Md Ashik; Loh, Zhixuan; Gan, Wan Jun; Zhang, Vivian; Yang, Huan; Li, Jian Hua; Yamamoto, Yasuhiko; Schmidt, Ann Marie; Armour, Carol L; Hughes, J Margaret; Phipps, Simon; Sukkar, Maria B

2014-08-01

The receptor for advanced glycation end products (RAGE) shares common ligands and signaling pathways with TLR4, a key mediator of house dust mite (Dermatophagoides pteronyssinus) (HDM) sensitization. We hypothesized that RAGE and its ligand high-mobility group box-1 (HMGB1) cooperate with TLR4 to mediate HDM sensitization. To determine the requirement for HMGB1 and RAGE, and their relationship with TLR4, in airway sensitization. TLR4(-/-), RAGE(-/-), and RAGE-TLR4(-/-) mice were intranasally exposed to HDM or cockroach (Blatella germanica) extracts, and features of allergic inflammation were measured during the sensitization or challenge phase. Anti-HMGB1 antibody and the IL-1 receptor antagonist Anakinra were used to inhibit HMGB1 and the IL-1 receptor, respectively. The magnitude of allergic airway inflammation in response to either HDM or cockroach sensitization and/or challenge was significantly reduced in the absence of RAGE but not further diminished in the absence of both RAGE and TLR4. HDM sensitization induced the release of HMGB1 from the airway epithelium in a biphasic manner, which corresponded to the sequential activation of TLR4 then RAGE. Release of HMGB1 in response to cockroach sensitization also was RAGE dependent. Significantly, HMGB1 release occurred downstream of TLR4-induced IL-1α, and upstream of IL-25 and IL-33 production. Adoptive transfer of HDM-pulsed RAGE(+/+)dendritic cells to RAGE(-/-) mice recapitulated the allergic responses after HDM challenge. Immunoneutralization of HMGB1 attenuated HDM-induced allergic airway inflammation. The HMGB1-RAGE axis mediates allergic airway sensitization and airway inflammation. Activation of this axis in response to different allergens acts to amplify the allergic inflammatory response, which exposes it as an attractive target for therapeutic intervention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model.

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Konrad Urbanek

Full Text Available The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce.To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model.GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro.Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties.Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue

The New Perilaryngeal Airway (CobraPLA™)1 Is as Efficient as the Laryngeal Mask Airway (LMA™)2, But Provides Better Airway Sealing Pressures

Science.gov (United States)

Akça, Ozan; Wadhwa, Anupama; Sengupta, Papiya; Durrani, Jaleel; Hanni, Keith; Wenke, Mary; Yücel, Yüksel; Lenhardt, Rainer; Doufas, Anthony G.; Sessler, Daniel I.

2006-01-01

The Laryngeal Mask Airway (LMA) is a frequently-used efficient airway device, yet it sometimes seals poorly, thus reducing the efficacy of positive-pressure ventilation. The Perilaryngeal Airway (CobraPLA) is a novel airway device with a larger pharyngeal cuff (when inflated). We tested the hypothesis that the CobraPLA was superior to LMA with regard to insertion time and airway sealing pressure and comparable to LMA in airway adequacy and recovery characteristics. After midazolam and fentanyl, 81 ASA I-II outpatients having elective surgery were randomized to receive an LMA or CobraPLA. Anesthesia was induced with propofol (2.5 mg/kg, IV), and the airway inserted. We measured 1) insertion time; 2) adequacy of the airway (no leak at 15-cm-H2O peak pressure or tidal volume of 5 ml/kg); 3) airway sealing pressure; 4) number of repositioning attempts; and 5) sealing quality (no leak at tidal volume of 8 ml/kg). At the end of surgery, gastric insufflation, postoperative sore throat, dysphonia, and dysphagia were evaluated. Data were compared with unpaired t-tests, chi-square tests, or Fisher’s Exact tests; P<0.05 was significant. Patient characteristics, insertion times, airway adequacy, number of repositioning attempts, and recovery were similar in each group. Airway sealing pressure was significantly greater with CobraPLA (23±6 cm H2O) than LMA (18±5 cm H2O, P<0.001). The CobraPLA has insertion characteristics similar to LMA, but better airway sealing capabilities. PMID:15281543

Histone deacetylase inhibitors up-regulate LL-37 expression independent of toll-like receptor mediated signalling in airway epithelial cells

NARCIS (Netherlands)

Liu, Quan; Liu, Juan; Roschmann, Kristina Irene Lisolette; van Egmond, Danielle; Golebski, Korneliusz; Fokkens, Wytske Johanna; Wang, Dehui; van Drunen, Cornelis Maria

2013-01-01

HDAC inhibitors have been proposed as anticancer agents. However, their roles in innate genes expression remain not well known. Cathelicidin LL-37 is one of the few human bactericidal peptides, but the regulation of histone acetylation on LL-37 expression in airway epithelium remains largely

dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses.

Science.gov (United States)

Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

2017-08-04

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

Endoscopic diode-laser applications in airway surgery

Science.gov (United States)

Pankratov, Michail M.; Wang, Zhi; Rebeiz, Elie E.; Perrault, Donald F., Jr.; Shapshay, Stanley M.; Gleich, Lyon L.

1994-09-01

A technique was developed to secure small mucosal grafts onto the airway wound with fibrin/albumin tissue adhesive mixed with ICG dye and irradiated with a 810 nm diode laser. An in vitro study of the tensile strength produced strong mucosal soldering which was adequate to fix grafts in place. In vivo studies showed that wounds with mucosal grafts were completely covered by regenerated squamous cells in 1 week and by ciliated epithelium in 2 weeks. Excellent healing was observed at 6 and 14 days postoperatively and the histology at 28 days found normal epithelium over the vocal cord lesion. This soldering technique is a less traumatic treatment for patients with extensive lesions of the larynx of various origin. Diode laser soldering with ICG-doped fibrin tissue adhesive was evaluated in tracheal anastomosis as a substitute for absorbable sutures. In vitro studies demonstrated strong anastomoses with minimal tissue damage. In vivo animal study showed that these anastomoses had less fibrosis and tissue damage than control animals repaired with sutures only.

Dioscorin pre-treatment protects A549 human airway epithelial cells from hydrogen peroxide-induced oxidative stress.

Science.gov (United States)

Hsu, Jeng-Yuan; Chu, Jao-Jia; Chou, Ming-Chih; Chen, Ya-Wen

2013-10-01

Hydrogen peroxide (H(2)O(2)) is a highly reactive oxygen species involved in lung and bronchial epithelium injury. Increased H(2)O(2) levels have been reported in expired breath condensates of patients with inflammatory airway diseases such as chronic obstructive pulmonary disease. Protecting airway epithelial cells from oxidative stress is an important task in the prevention and management of airway diseases. Previous studies demonstrate that yam (Dioscorea batatas Decne) has antioxidant and anti-trypsin activities. This study evaluated the validity of dioscorin in vitro. The results showed that dioscorin attenuated the alteration of H(2)O(2) on G2/M cell cycle arrest. This might be associated with the activation of IκB and subsequent inactivation of NF-κB. Furthermore, dioscorin suppressed IL-8 secretion and reduced changes of adhesion molecule expressions in H(2)O(2)-injured A549 cells. These results help in understanding the potential of traditional Chinese herbal medicine as treatment for airway inflammatory diseases.

Quantitative study of the penetration of insoluble particles into the tissue of the conducting airways

Energy Technology Data Exchange (ETDEWEB)

Gore, D J; Patrick, G [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1982-01-01

A quantitative study is presented of the spatial distribution of both inhaled UO/sub 2/ particles and intra-tracheally administered BaSO/sub 4/ particles in the wall of the airways in the rat. The results show that in the intrapulmonary airways between 7 and 17 days after inhalation, UO/sub 2/ particles are situated most frequently at a depth of 8-10 ..mu..m from the luminal surface. At 24 h in the trachea, BaSO/sub 4/ particles concentrate between 10 and 15 ..mu..m beneath the surface, corresponding to the zone immediately beneath the basement membrane; by 7 days the distribution is broader but otherwise similar. This pattern of retention should assist in assessing the dose from radioactive particles absorbed by the basal cells of the epithelium, which are likely to be the origin of carcinoma of the airways.

Increase of corneal epithelium cell radioresistance during regeneration

International Nuclear Information System (INIS)

Popova, M.F.; Bulyakova, N.V.; Azarova, V.S.

1985-01-01

A comparative study of the radiosensitivity of the normal and regenerating cornea epithelium of C 57 Bl mice was performed on the cellular level, the duration of the cell cycle being taken into account. Criteria of radiation injuries were the number of chromosome aberrations, mitotic index and duration of mitotic block. The anterior part of the head was irradiated singly with 1.75, 3.5 or 7.0 Gy and also repeatedly 3.5 + 3.5 at a 24-hours interval. The corneas were fixed 2, 4, 6, 12, 24, 48, 72 and 96 hours after irradiation. In all cases of irradiated mice the regenerating epithelium showed a shorter mitotic block and significantly lower cytogenetic injury as compared with the controls. Effects of fractionated irradiation were only shown in the regenerating epithelium. The results obtained indicate that regenerating epithelium cells of the cornea are significantly more radioresistant than normal epithelium due to activation of post-radiation recovery, and also, possibly, due to an increase in the content of endogenous radioprotectors. (author)

Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease.

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Royce, Simon G; Dang, William; Ververis, Katherine; De Sampayo, Nishika; El-Osta, Assam; Tang, Mimi L K; Karagiannis, Tom C

2011-12-01

Airway remodeling and airway hyperresponsiveness are major aspects of asthma pathology that are not targeted optimally by existing anti-inflammatory drugs. Histone deacetylase inhibitors have a wide range of effects that may potentially abrogate aspects of remodeling. One such histone deacetylase inhibitor is valproic acid (2-propylvaleric acid). Valproic acid is used clinically as an anti-epileptic drug and is a potent inhibitor of class I histone deacetylases but also inhibits class II histone deacetylases. We used valproic acid as a molecular model of histone deacetylase inhibition in vivo in chronic allergic airways disease mice with airway remodeling and airway hyperresponsiveness. Wild-type Balb/c mice with allergic airways disease were treated with valproic acid or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and examination of lung tissue sections. Remodeling was assessed by morphometric analysis of histochemically stained slides and lung function was assessed by invasive plethysmography measurement of airway resistance. Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0.01), reduced subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness (p < 0.05 and p < 0.01 for the two highest doses of methacholine, respectively). These findings show that treatment with valproic acid can reduce structural airway remodeling changes and hyperresponsiveness, providing further evidence for the potential use of histone deacetylase inhibitors for the treatment of asthma.

EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium

NARCIS (Netherlands)

Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J.; Roschmann, Kristina I. L.; Fokkens, Wytske J.; van Drunen, Cornelis M.

2015-01-01

Background: Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. Objective: To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could

Automatic airway-artery analysis on lung CT to quantify airway wall thickening and bronchiectasis

DEFF Research Database (Denmark)

Perez-Rovira, Adria; Kuo, Wieying; Petersen, Jens

2016-01-01

Purpose: Bronchiectasis and airway wall thickening are commonly assessed in computed tomography (CT) by comparing the airway size with the size of the accompanying artery. Thus, in order to automate the quantification of bronchiectasis and wall thickening following a similar principle......, and pairs airway branches with the accompanying artery, then quantifies airway wall thickening and bronchiectasis by measuring the wall-artery ratio (WAR) and lumen and outer wall airway-artery ratio (AAR). Measurements that do not use the artery size for normalization are also extracted, including wall...... area percentage (WAP), wall thickness ratio (WTR), and airway diameters. Results: The method was thoroughly evaluated using 8000 manual annotations of airway-artery pairs from 24 full-inspiration pediatric CT scans (12 diseased and 12 controls). Limits of agreement between the automatically...

Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma.

Science.gov (United States)

Işık, S; Karaman, M; Çilaker Micili, S; Çağlayan-Sözmen, Ş; Bağrıyanık, H Alper; Arıkan-Ayyıldız, Z; Uzuner, N; Karaman, Ö

In previous studies, anti-inflammatory, anti-apoptotic and immunomodulatory effects of ursodeoxycholic acid (UDCA) on liver diseases have been shown. In this study, we aimed to investigate the effects of UDCA on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. Twenty-seven BALB/c mice were divided into five groups; PBS-Control, OVA-Placebo, OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone received the UDCA (50mg/kg), UDCA (150mg/kg), and dexamethasone, respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide, ovalbumin-specific immunoglobulin (Ig) E levels were quantified. The dose of 150mg/kg UDCA treatment led to lower epithelial thickness, sub-epithelial smooth muscle thickness, goblet and mast cell numbers compared to placebo. Except for MMP-9 and TUNEL all immunohistochemical scores were similar in both UDCA treated groups and the placebo. All cytokine levels were significantly lower in group IV compared to the placebo. These findings suggested that the dose of 150mg/kg UDCA improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma.

Science.gov (United States)

Singhania, Akul; Wallington, Joshua C; Smith, Caroline G; Horowitz, Daniel; Staples, Karl J; Howarth, Peter H; Gadola, Stephan D; Djukanović, Ratko; Woelk, Christopher H; Hinks, Timothy S C

2018-02-01

Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3 + T cells from sputum and BAL were obtained from healthy subjects (n = 19) and patients with asthma (mild, moderate, and severe asthma; n = 46). Gene expression was assessed using Affymetrix HT HG-U133 + PM GeneChips, and results were validated by real-time quantitative PCR. In the epithelium, IL-13 response genes (POSTN, SERPINB2, and CLCA1), mast cell mediators (CPA3 and TPSAB1), inducible nitric oxide synthase, and cystatins (CST1, CST2, and CST4) were upregulated in mild asthma, but, except for cystatins, were suppressed by corticosteroids in moderate asthma. In severe asthma-with predominantly neutrophilic phenotype-several distinct processes were upregulated, including neutrophilia (TCN1 and MMP9), mucins, and oxidative stress responses. The majority of the disease signature was evident in sputum T cells in severe asthma, where 267 genes were differentially regulated compared with health, highlighting compartmentalization of inflammation. This signature included IL-17-inducible chemokines (CXCL1, CXCL2, CXCL3, IL8, and CSF3) and chemoattractants for neutrophils (IL8, CCL3, and LGALS3), T cells, and monocytes. A protein interaction network in severe asthma highlighted signatures of responses to bacterial infections across tissues (CEACAM5, CD14, and TLR2), including Toll-like receptor signaling. In conclusion, the activation of innate immune pathways in the airways suggests that activated T cells may be driving neutrophilic inflammation and steroid-insensitive IL-17 response in severe asthma.

Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP) and CCL11/eotaxin-1 in human asthmatic airways.

Science.gov (United States)

Nino, Gustavo; Huseni, Shehlanoor; Perez, Geovanny F; Pancham, Krishna; Mubeen, Humaira; Abbasi, Aleeza; Wang, Justin; Eng, Stephen; Colberg-Poley, Anamaris M; Pillai, Dinesh K; Rose, Mary C

2014-01-01

Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC) from normal (n = 3) and asthmatic (n = 3) donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20) vs. non-asthmatic uninfected controls (n = 20). Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. Our data demonstrate that: 1) Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2) TSLP exposure induces unidirectional (apical) secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3) Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP and CCL11/eotaxin-1 in human asthmatic airways.

Directory of Open Access Journals (Sweden)

Gustavo Nino

Full Text Available Thymic stromal lymphoproetin (TSLP is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state.Primary human bronchial epithelial cells (HBEC from control (n = 3 and asthmatic (n = 3 donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI conditions and treated apically with dsRNA (viral surrogate or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC from normal (n = 3 and asthmatic (n = 3 donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20 vs. non-asthmatic uninfected controls (n = 20. Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay.Our data demonstrate that: 1 Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2 TSLP exposure induces unidirectional (apical secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3 Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1.There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling

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Park Chang-Soo

2006-02-01

Full Text Available Abstract Background Short-term exposure to high concentrations of ozone has been shown to increase airway hyper-responsiveness (AHR. Because the changes in AHR and airway inflammation and structure after chronic ozone exposure need to be determined, the goal of this study was to investigate these effects in a murine model of allergic airway disease. Methods We exposed BALB/c mice to 2 ppm ozone for 4, 8, and 12 weeks. We measured the enhanced pause (Penh to methacholine and performed cell differentials in bronchoalveolar lavage fluid. We quantified the levels of IL-4 and IFN-γ in the supernatants of the bronchoalveolar lavage fluids using enzyme immunoassays, and examined the airway architecture under light and electron microscopy. Results The groups exposed to ozone for 4, 8, and 12 weeks demonstrated decreased Penh at methacholine concentrations of 12.5, 25, and 50 mg/ml, with a dose-response curve to the right of that for the filtered-air group. Neutrophils and eosinophils increased in the group exposed to ozone for 4 weeks compared to those in the filtered-air group. The ratio of IL-4 to INF-γ increased significantly after exposure to ozone for 8 and 12 weeks compared to the ratio for the filtered-air group. The numbers of goblet cells, myofibroblasts, and smooth muscle cells showed time-dependent increases in lung tissue sections from the groups exposed to ozone for 4, 8, and 12 weeks. Conclusion These findings demonstrate that the increase in AHR associated with the allergic airway does not persist during chronic ozone exposure, indicating that airway remodeling and adaptation following repeated exposure to air pollutants can provide protection against AHR.

Characterization of endocytosis and exocytosis of cationic nanoparticles in airway epithelium cells

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Dombu, Christophe Youta; Kroubi, Maya; Zibouche, Rima; Matran, Regis; Betbeder, Didier, E-mail: dbetbeder@aol.com [EA 4483, IFR 114, Laboratoire de Physiologie, Faculte de Medecine Pole Recherche, Universite de Lille 2, 1 place de Verdun, 59045 Lille Cedex (France)

2010-09-03

A major challenge of drug delivery using colloids via the airway is to understand the mechanism implied in their interactions with epithelial cells. The purpose of this work was to characterize the process of endocytosis and exocytosis of cationic nanoparticles (NPs) made of maltodextrin which were developed as a delivery system for antigens in vaccine applications. Confocal microscopy demonstrated that these NP are rapidly endocytosed after as little as 3 min incubation, and that the endocytosis was also faster than NP binding since most of the NPs were found in the middle of the cells around the nuclei. A saturation limit was observed after a 40 min incubation, probably due to an equilibrium becoming established between endocytosis and exocytosis. Endocytosis was dramatically reduced at 4 deg. C compared with 37 deg. C, or by NaN{sub 3} treatment, both results suggesting an energy dependent process. Protamine pretreatment of the cells inhibited NPs uptake and we found that clathrin pathway is implied in their endocytosis. Cholesterol depletion increased NP uptake by 300% and this phenomenon was explained by the fact that cholesterol depletion totally blocked NP exocytosis. These results suggest that these cationic NPs interact with anionic sites, are quickly endocytosed via the clathrin pathway and that their exocytosis is cholesterol dependent, and are similar to those obtained in other studies with viruses such as influenza.

Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey

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Buckpitt, Alan, E-mail: arbuckpitt@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Morin, Dexter [Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura [Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Center for Health and the Environment, UC Davis, Davis, CA 95616 United States (United States)

2013-07-15

Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent K{sub m}, V{sub max}, and catalytic efficiency (V{sub max}/K{sub m}) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar K{sub m} and V{sub max} appeared to metabolize naphthalene. The rank order of V{sub max} (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The V{sub max} in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly.

High rhinovirus burden in lower airways of children with cystic fibrosis.

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Kieninger, Elisabeth; Singer, Florian; Tapparel, Caroline; Alves, Marco P; Latzin, Philipp; Tan, Hui-Leng; Bossley, Cara; Casaulta, Carmen; Bush, Andrew; Davies, Jane C; Kaiser, Laurent; Regamey, Nicolas

2013-03-01

Rhinovirus (RV)-induced pulmonary exacerbations are common in cystic fibrosis (CF) and have been associated with impaired virus clearance by the CF airway epithelium in vitro. Here, we assess in vivo the association of RV prevalence and load with antiviral defense mechanisms, airway inflammation, and lung function parameters in children with CF compared with a control group and children with other chronic respiratory diseases. RV presence and load were measured by real-time reverse transcription-polymerase chain reaction in BAL samples and were related to antiviral and inflammatory mediators measured in BAL and to clinical parameters. BAL samples were obtained from children with CF (n = 195), non-CF bronchiectasis (n = 40), or asthma (n = 29) and from a control group (n = 35) at a median (interquartile range [IQR]) age of 8.2 (4.0-11.7) years. RV was detected in 73 samples (24.4%). RV prevalence was similar among groups. RV load (median [IQR] x 10(3) copies/mL) was higher in children with CF (143.0 [13.1-1530.0]), especially during pulmonary exacerbations, compared with children with asthma (3.0 [1.3-25.8], P = .006) and the control group (0.5 [0.3-0.5], P < .001), but similar to patients with non-CF bronchiectasis (122.1 [2.7-4423.5], P = not significant). In children with CF, RV load was negatively associated with interferon (IFN)- b and IFN- l , IL-1ra levels, and FEV 1 , and positively with levels of the cytokines CXCL8 and CXCL10. RV load in CF BAL is high, especially during exacerbated lung disease. Impaired production of antiviral mediators may lead to the high RV burden in the lower airways of children with CF. Whether high RV load is a cause or a consequence of inflammation needs further investigation in longitudinal studies.

Toll-8/Tollo negatively regulates antimicrobial response in the Drosophila respiratory epithelium.

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Idir Akhouayri

2011-10-01

Full Text Available Barrier epithelia that are persistently exposed to microbes have evolved potent immune tools to eliminate such pathogens. If mechanisms that control Drosophila systemic responses are well-characterized, the epithelial immune responses remain poorly understood. Here, we performed a genetic dissection of the cascades activated during the immune response of the Drosophila airway epithelium i.e. trachea. We present evidence that bacteria induced-antimicrobial peptide (AMP production in the trachea is controlled by two signalling cascades. AMP gene transcription is activated by the inducible IMD pathway that acts non-cell autonomously in trachea. This IMD-dependent AMP activation is antagonized by a constitutively active signalling module involving the receptor Toll-8/Tollo, the ligand Spätzle2/DNT1 and Ect-4, the Drosophila ortholog of the human Sterile alpha and HEAT/ARMadillo motif (SARM. Our data show that, in addition to Toll-1 whose function is essential during the systemic immune response, Drosophila relies on another Toll family member to control the immune response in the respiratory epithelium.

The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

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Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

2014-05-02

The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium.

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Kamdar, O; Le, Wei; Zhang, J; Ghio, A J; Rosen, G D; Upadhyay, D

2008-10-29

We studied the effects of airborne particulate matters (PM) on cystic fibrosis (CF) epithelium. We noted that PM enhanced human CF bronchial epithelial apoptosis, activated caspase-9 and PARP-1; and reduced mitochondrial membrane potential. Mitochondrial inhibitors (4,4-diisothiocyanatostilbene-2,2'disulfonic acid, rotenone and thenoyltrifluoroacetone) blocked PM-induced generation of reactive oxygen species and apoptosis. PM upregulated pro-apoptotic Bad, Bax, p53 and p21; and enhanced mitochondrial localization of Bax. The anti-apoptotic Bcl-2, Bcl-xl, Mcl-1 and Xiap remained unchanged; however, overexpression of Bcl-xl blocked PM-induced apoptosis. Accordingly, we provide the evidence that PM enhances oxidative stress and mitochondrial signaling mediated apoptosis via the modulation of Bcl family proteins in CF.

Integrated care pathways for airway diseases (AIRWAYS-ICPs)

DEFF Research Database (Denmark)

Bousquet, J; Addis, A; Adcock, I

2014-01-01

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy...... and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking...... and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5...

Airway injury during emergency transcutaneous airway access: a comparison at cricothyroid and tracheal sites.

LENUS (Irish Health Repository)

Salah, Nazar

2009-12-01

Oxygenation via the cricothyroid membrane (CTM) may be required in emergencies, but inadvertent tracheal cannulation may occur. In this study, we compared airway injury between the tracheal and CTM sites using different techniques for airway access.

Human airway organoid engineering as a step toward lung regeneration and disease modeling.

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Tan, Qi; Choi, Kyoung Moo; Sicard, Delphine; Tschumperlin, Daniel J

2017-01-01

Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture. After condensation airway organoids generate invasive multicellular tubular structures that recapitulate limited aspects of branching morphogenesis, and require actomyosin-mediated force generation and YAP/TAZ activation. Despite the proximal source of primary epithelium used in the airway organoids, discrete areas of both proximal and distal epithelial markers were observed over time in culture, demonstrating remarkable epithelial plasticity within the context of organoid cultures. Airway organoids also exhibited complex multicellular responses to a prototypical fibrogenic stimulus (TGF-β1) in culture, and limited capacity to undergo continued maturation and engraftment after ectopic implantation under the murine kidney capsule. These results demonstrate that the airway organoid system developed here represents a novel tool for the study of disease-relevant cell-cell interactions, and establishes this platform as a first step toward cell-based therapy for chronic lung diseases based on de novo engineering of implantable airway tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytokeratin expression in mouse lacrimal gland germ epithelium.

Science.gov (United States)

Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

2016-05-01

The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis.

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Sandefur, Conner I; Boucher, Richard C; Elston, Timothy C

2017-08-29

Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease. A systems-level description of airway surface liquid (ASL) homeostasis could accelerate development of such therapies. Accordingly, we developed a mathematical model to describe the dynamic coupling of ion and water transport to extracellular purinergic signaling. We trained our model from steady-state and time-dependent experimental measurements made using normal and cystic fibrosis (CF) cultured human airway epithelium. To reproduce CF conditions, reduced chloride secretion, increased potassium secretion, and increased sodium absorption were required. The model accurately predicted ASL height under basal normal and CF conditions and the collapse of surface hydration due to the accelerated nucleotide metabolism associated with CF exacerbations. Finally, the model predicted a therapeutic strategy to deliver nucleotide receptor agonists to effectively rehydrate the ASL of CF airways.

Airway necrosis after salvage esophagectomy

International Nuclear Information System (INIS)

Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

2010-01-01

Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive chemoradiotherapy (CRT) for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Between 1997 and 2007, 49 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT. We retrospectively compared patients with and without airway necrosis, and investigated operative procedures related to airway necrosis. Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery and cervical and subcarinal lymph node dissection. Bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. (author)

Expression of taste receptors in Solitary Chemosensory Cells of rodent airways

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Sbarbati Andrea

2011-01-01

Full Text Available Abstract Background Chemical irritation of airway mucosa elicits a variety of reflex responses such as coughing, apnea, and laryngeal closure. Inhaled irritants can activate either chemosensitive free nerve endings, laryngeal taste buds or solitary chemosensory cells (SCCs. The SCC population lies in the nasal respiratory epithelium, vomeronasal organ, and larynx, as well as deeper in the airway. The objective of this study is to map the distribution of SCCs within the airways and to determine the elements of the chemosensory transduction cascade expressed in these SCCs. Methods We utilized a combination of immunohistochemistry and molecular techniques (rtPCR and in situ hybridization on rats and transgenic mice where the Tas1R3 or TRPM5 promoter drives expression of green fluorescent protein (GFP. Results Epithelial SCCs specialized for chemoreception are distributed throughout much of the respiratory tree of rodents. These cells express elements of the taste transduction cascade, including Tas1R and Tas2R receptor molecules, α-gustducin, PLCβ2 and TrpM5. The Tas2R bitter taste receptors are present throughout the entire respiratory tract. In contrast, the Tas1R sweet/umami taste receptors are expressed by numerous SCCs in the nasal cavity, but decrease in prevalence in the trachea, and are absent in the lower airways. Conclusions Elements of the taste transduction cascade including taste receptors are expressed by SCCs distributed throughout the airways. In the nasal cavity, SCCs, expressing Tas1R and Tas2R taste receptors, mediate detection of irritants and foreign substances which trigger trigeminally-mediated protective airway reflexes. Lower in the respiratory tract, similar chemosensory cells are not related to the trigeminal nerve but may still trigger local epithelial responses to irritants. In total, SCCs should be considered chemoreceptor cells that help in preventing damage to the respiratory tract caused by inhaled irritants and

Expression of taste receptors in solitary chemosensory cells of rodent airways.

Science.gov (United States)

Tizzano, Marco; Cristofoletti, Mirko; Sbarbati, Andrea; Finger, Thomas E

2011-01-13

Chemical irritation of airway mucosa elicits a variety of reflex responses such as coughing, apnea, and laryngeal closure. Inhaled irritants can activate either chemosensitive free nerve endings, laryngeal taste buds or solitary chemosensory cells (SCCs). The SCC population lies in the nasal respiratory epithelium, vomeronasal organ, and larynx, as well as deeper in the airway. The objective of this study is to map the distribution of SCCs within the airways and to determine the elements of the chemosensory transduction cascade expressed in these SCCs. We utilized a combination of immunohistochemistry and molecular techniques (rtPCR and in situ hybridization) on rats and transgenic mice where the Tas1R3 or TRPM5 promoter drives expression of green fluorescent protein (GFP). Epithelial SCCs specialized for chemoreception are distributed throughout much of the respiratory tree of rodents. These cells express elements of the taste transduction cascade, including Tas1R and Tas2R receptor molecules, α-gustducin, PLCβ2 and TrpM5. The Tas2R bitter taste receptors are present throughout the entire respiratory tract. In contrast, the Tas1R sweet/umami taste receptors are expressed by numerous SCCs in the nasal cavity, but decrease in prevalence in the trachea, and are absent in the lower airways. Elements of the taste transduction cascade including taste receptors are expressed by SCCs distributed throughout the airways. In the nasal cavity, SCCs, expressing Tas1R and Tas2R taste receptors, mediate detection of irritants and foreign substances which trigger trigeminally-mediated protective airway reflexes. Lower in the respiratory tract, similar chemosensory cells are not related to the trigeminal nerve but may still trigger local epithelial responses to irritants. In total, SCCs should be considered chemoreceptor cells that help in preventing damage to the respiratory tract caused by inhaled irritants and pathogens.

Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity.

Science.gov (United States)

Park, So Young; Hong, Gyong Hwa; Park, Sunjoo; Shin, Bomi; Yoon, Sun-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

2016-12-01

Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. To investigate the association between serum progranulin levels and various clinical features in patients with asthma. Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma. Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comparative Assessment of Three Approaches of Teaching Nonmedically Trained Persons in the Handling of Supraglottic Airways: A Randomized Controlled Trial.

Science.gov (United States)

Hensel, Mario; Schmidbauer, Willi; Benker, Michael; Schmieder, Paula; Kerner, Thoralf

2017-03-01

The use of supraglottic airways has been recommended in combat trauma airway management. To ensure an adequate airway management on the battlefield, suitable training concepts are sought to efficiently teach as many soldiers as possible. Our aim was to compare three approaches of teaching laypersons in the handling of supraglottic airways in a mannequin model. In this prospective randomized blinded study, 285 military service men without any medical background were divided into three groups and trained in the use of the Laryngeal Mask Airway Supreme (LMA) and the Laryngeal Tube Disposable (LT-D). The first group received a theoretical lecture, the second group was shown an instruction video, and the third group underwent a practical training. Immediately after instruction participants were asked to place the supraglottic airway and ventilate the mannequin within 60 seconds. The entire test was repeated 3 months later. Test results were evaluated with regard to success rate, insertion time, ability to judge the correct placement, and degree of difficulty. Practical training showed the highest success rate when placing supraglottic airways immediately after the instruction (lecture: 68%, video: 74%, training: 94%); (training vs. lecture and training vs. video, p training: 78%); (training vs. lecture, p = 0.019 and training vs. video, p = 0.025). Immediately after the instruction practical training was also superior in terms of insertion time, ability to judge the correct placement, and the self-rated degree of difficulty (p place a supraglottic airway immediately following minimal instruction and after 3 months as well. Study participants achieved the best results after practical training followed by video presentation and finally lecture regardless of the airway device used. There are two possible reasons why practical training is the superior method. Firstly, the success is tied to more time spent with the learners. Secondly, practical training seems to be the best

Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

International Nuclear Information System (INIS)

Xu, Yuan; Cardell, Lars-Olaf

2014-01-01

Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B 2 receptor agonist) and des-Arg 9 -bradykinin- (selective B 1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE 2 . The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg 9 -bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B 2 receptors, but not those on B 1 . Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in some patients with asthma

Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

Energy Technology Data Exchange (ETDEWEB)

Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

2014-02-15

Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

Pediatric Trainees Managing a Difficult Airway: Comparison of Laryngeal Mask Airway, Direct, and Video-Assisted Laryngoscopy

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Art Ambrosio MD

2017-05-01

Full Text Available Objective Difficult airway management is a key skill required by all pediatric physicians, yet training on multiple modalities is lacking. The objective of this study was to compare the rate of, and time to, successful advanced infant airway placement with direct laryngoscopy, video-assisted laryngoscopy, and laryngeal mask airway (LMA in a difficult airway simulator. This study is the first to compare the success with 3 methods for difficult airway management among pediatric trainees. Study Design Randomized crossover pilot study. Setting Tertiary academic medical center. Methods Twenty-two pediatric residents, interns, and medical students were tested. Participants were provided 1 training session by faculty using a normal infant manikin. Subjects then performed all 3 of the aforementioned advanced airway modalities in a randomized order on a difficult airway model of a Robin sequence. Success was defined as confirmed endotracheal intubation or correct LMA placement by the testing instructor in ≤120 seconds. Results Direct laryngoscopy demonstrated a significantly higher placement success rate (77.3% than video-assisted laryngoscopy (36.4%, P = .0117 and LMA (31.8%, P = .0039. Video-assisted laryngoscopy required a significantly longer amount of time during successful intubations (84.8 seconds; 95% CI, 59.4-110.1 versus direct laryngoscopy (44.9 seconds; 95% CI, 33.8-55.9 and LMA placement (36.6 seconds; 95% CI, 24.7-48.4. Conclusions Pediatric trainees demonstrated significantly higher success using direct laryngoscopy in a difficult airway simulator model. However, given the potential lifesaving implications of advanced airway adjuncts, including video-assisted laryngoscopy and LMA placement, more extensive training on adjunctive airway management techniques may be useful for trainees.

Allergic rhinitis and asthma: inflammation in a one-airway condition

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Haahtela Tari

2006-11-01

Full Text Available Abstract Background Allergic rhinitis and asthma are conditions of airway inflammation that often coexist. Discussion In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria. Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli. Structural alterations (that is, remodeling of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened. Conclusion Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites.

Upper airway morphology in Down Syndrome patients under dexmedetomidine sedation

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Rajeev Subramanyam

Full Text Available Abstract Background and objectives: Children with Down Syndrome are vulnerable to significant upper airway obstruction due to relative macroglossia and dynamic airway collapse. The objective of this study was to compare the upper airway dimensions of children with Down Syndrome and obstructive sleep apnea with normal airway under dexmedetomidine sedation. Methods: IRB approval was obtained. In this retrospective study, clinically indicated dynamic sagittal midline magnetic resonance images of the upper airway were obtained under low (1 mcg/kg/h and high (3 mcg/kg/h dose dexmedetomidine. Airway anteroposterior diameters and sectional areas were measured as minimum and maximum dimensions by two independent observers at soft palate (nasopharyngeal airway and at base of the tongue (retroglossal airway. Results and conclusions: Minimum anteroposterior diameter and minimum sectional area at nasopharynx and retroglossal airway were significantly reduced in Down Syndrome compared to normal airway at both low and high dose dexmedetomidine. However, there were no significant differences between low and high dose dexmedetomidine in both Down Syndrome and normal airway. The mean apnea hypopnea index in Down Syndrome was 16 ± 11. Under dexmedetomidine sedation, children with Down Syndrome and obstructive sleep apnea when compared to normal airway children show significant reductions in airway dimensions most pronounced at the narrowest points in the nasopharyngeal and retroglossal airways.

Upper airway morphology in Down Syndrome patients under dexmedetomidine sedation.

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Subramanyam, Rajeev; Fleck, Robert; McAuliffe, John; Radhakrishnan, Rupa; Jung, Dorothy; Patino, Mario; Mahmoud, Mohamed

2016-01-01

Children with Down Syndrome are vulnerable to significant upper airway obstruction due to relative macroglossia and dynamic airway collapse. The objective of this study was to compare the upper airway dimensions of children with Down Syndrome and obstructive sleep apnea with normal airway under dexmedetomidine sedation. IRB approval was obtained. In this retrospective study, clinically indicated dynamic sagittal midline magnetic resonance images of the upper airway were obtained under low (1mcg/kg/h) and high (3mcg/kg/h) dose dexmedetomidine. Airway anteroposterior diameters and sectional areas were measured as minimum and maximum dimensions by two independent observers at soft palate (nasopharyngeal airway) and at base of the tongue (retroglossal airway). Minimum anteroposterior diameter and minimum sectional area at nasopharynx and retroglossal airway were significantly reduced in Down Syndrome compared to normal airway at both low and high dose dexmedetomidine. However, there were no significant differences between low and high dose dexmedetomidine in both Down Syndrome and normal airway. The mean apnea hypopnea index in Down Syndrome was 16±11. Under dexmedetomidine sedation, children with Down Syndrome and obstructive sleep apnea when compared to normal airway children show significant reductions in airway dimensions most pronounced at the narrowest points in the nasopharyngeal and retroglossal airways. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Upper airway morphology in Down Syndrome patients under dexmedetomidine sedation].

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Subramanyam, Rajeev; Fleck, Robert; McAuliffe, John; Radhakrishnan, Rupa; Jung, Dorothy; Patino, Mario; Mahmoud, Mohamed

2016-01-01

Children with Down Syndrome are vulnerable to significant upper airway obstruction due to relative macroglossia and dynamic airway collapse. The objective of this study was to compare the upper airway dimensions of children with Down Syndrome and obstructive sleep apnea with normal airway under dexmedetomidine sedation. IRB approval was obtained. In this retrospective study, clinically indicated dynamic sagittal midline magnetic resonance images of the upper airway were obtained under low (1mcg/kg/h) and high (3mcg/kg/h) dose dexmedetomidine. Airway anteroposterior diameters and sectional areas were measured as minimum and maximum dimensions by two independent observers at soft palate (nasopharyngeal airway) and at base of the tongue (retroglossal airway). Minimum anteroposterior diameter and minimum sectional area at nasopharynx and retroglossal airway were significantly reduced in Down Syndrome compared to normal airway at both low and high dose dexmedetomidine. However, there were no significant differences between low and high dose dexmedetomidine in both Down Syndrome and normal airway. The mean apnea hypopnea index in Down Syndrome was 16±11. Under dexmedetomidine sedation, children with Down Syndrome and obstructive sleep apnea when compared to normal airway children show significant reductions in airway dimensions most pronounced at the narrowest points in the nasopharyngeal and retroglossal airways. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma

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Zaagsma Johan

2006-01-01

Full Text Available Abstract Background Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO production – due to competition with neuronal NO-synthase (nNOS for the common substrate, L-arginine. Furthermore, in a guinea pig model of allergic asthma, airway arginase activity is markedly increased after the early asthmatic reaction (EAR, leading to deficiency of agonist-induced, epithelium-derived NO and subsequent airway hyperreactivity. In this study, we investigated whether increased arginase activity after the EAR affects iNANC nerve-derived NO production and airway smooth muscle relaxation. Methods Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz-induced relaxation was measured in tracheal open-ring preparations precontracted to 30% with histamine in the presence of 1 μM atropine and 3 μM indomethacin. The contribution of NO to EFS-induced relaxation was assessed by the nonselective NOS inhibitor Nω-nitro-L-arginine (L-NNA, 100 μM, while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA, 10 μM. Furthermore, the role of substrate availability to nNOS was measured in the presence of exogenous L-arginine (5.0 mM. Results At 6 h after ovalbumin-challenge (after the EAR, EFS-induced relaxation (ranging from 3.2 ± 1.1% at 0.5 Hz to 58.5 ± 2.2% at 16 Hz was significantly decreased compared to unchallenged controls (7.1 ± 0.8% to 75.8 ± 0.7%; P P P Conclusion The results clearly demonstrate that increased arginase activity after the allergen-induced EAR contributes to a deficiency of iNANC nerve-derived NO and decreased airway smooth muscle relaxation, presumably via increased substrate competition with nNOS.

Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia

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Wang, I-Ching; Zhang, Yufang; Snyder, Jonathan; Sutherland, Mardi J.; Burhans, Michael S.; Shannon, John M.; Park, Hyun Jung; Whitsett, Jeffrey A.; Kalinichenko, Vladimir V.

2010-01-01

Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation, differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibits lung maturation and causes respiratory failure after birth. However, the role of Foxm1 during postnatal lung morphogenesis remains unknown. In the present study, Foxm1 expression was detected in epithelial cells of conducting and peripheral airways and changing dynamically with lung maturation. To discern the biological role of Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant or FoxM1-ΔN) under the control of lung epithelial-specific SPC promoter was produced. Expression of the FoxM1-ΔN transgene during embryogenesis caused epithelial hyperplasia, inhibited lung sacculation and expression of the type II epithelial marker, pro-SPC. Expression of FoxM1-ΔN mutant during the postnatal period did not influence alveologenesis but caused focal airway hyperplasia and increased proliferation of Clara cells. Likewise, expression of FoxM1-ΔN mutant in conducting airways with Scgb1a1 promoter was sufficient to induce Clara cell hyperplasia. Furthermore, FoxM1-ΔN cooperated with activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1 altered lung sacculation, induced proliferation in the respiratory epithelium and accelerated lung tumor growth, indicating that precise regulation of Foxm1 is critical for normal lung morphogenesis and development of lung cancer. PMID:20816795

Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection.

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2017-07-01

We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium. Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided. We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up ( P  cancer-associated gene expression alterations between the two airway sites ( P  lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P  = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P  = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort. These results support that the airway epithelial field of lung cancer-associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Airway smooth muscle cells : regulators of airway inflammation

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Zuyderduyn, Suzanne

2007-01-01

Airways from asthmatic subjects are more responsive to bronchoconstrictive stimuli than airways from healthy subjects. Airway smooth muscle (ASM) cells mediate contraction of the airways by responding to the bronchoconstrictive stimuli, which was thought to be the primary role of ASM cells. In this

Effect of inhomogeneous activity distributions and airway geometry on cellular doses in radon lung dosimetry

International Nuclear Information System (INIS)

Szoke, Istvan; Balashazy, Imre; Farkas, Arpad; Hofmann, Werner

2007-01-01

The human tracheobronchial system has a very complex structure including cylindrical airway ducts connected by airway bifurcation units. The deposition of the inhaled aerosols within the airways exhibits a very inhomogeneous pattern. The formation of deposition hot spots near the carinal ridge has been confirmed by experimental and computational fluid and particle dynamics (CFPD) methods. In spite of these observations, current radon lung dosimetry models apply infinitely long cylinders as models of the airway system and assume uniform deposition of the inhaled radon progenies along the airway walls. The aim of this study is to investigate the effect of airway geometry and non-uniform activity distributions within bronchial bifurcations on cellular dose distributions. In order to answer these questions, the nuclear doses of the bronchial epithelium were calculated in three different irradiation situations. (1) First, CFPD methods were applied to calculate the distribution of the deposited alpha-emitting nuclides in a numerically constructed idealized airway bifurcation. (2) Second, the deposited radionuclides were randomly distributed along the surface of the above-mentioned geometry. (3) Finally, calculations were made in cylindrical geometries corresponding to the parent and daughter branches of the bifurcation geometry assuming random nuclide activity distribution. In all three models, the same 218 Po and 214 Po surface activities per tissue volumes were assumed. Two conclusions can be drawn from this analysis: (i) average nuclear doses are very similar in all three cases (minor differences can be attributed to differences in the linear energy transfer (LET) spectra) and (ii) dose distributions are significantly different in all three cases, with the highest doses at the carinal ridge in case 3. (authors)

Airway branching morphogenesis in three dimensional culture

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Gudjonsson Thorarinn

2010-11-01

form branching bronchioalveolar-like structures in 3-D culture. This novel model of human airway morphogenesis can be used to study critical events in human lung development and suggests a supportive role for the endothelium in promoting branching of airway epithelium.

Inherent and antigen-induced airway hyperreactivity in NC mice

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Tetsuto Kobayashi

1999-01-01

Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.

Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium.

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Amitani, R; Taylor, G; Elezis, E N; Llewellyn-Jones, C; Mitchell, J; Kuze, F; Cole, P J; Wilson, R

1995-09-01

The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.

Airway malacia in children with achondroplasia.

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Dessoffy, Kimberly E; Modaff, Peggy; Pauli, Richard M

2014-02-01

This study was undertaken to assess the frequency of airway malacia in infants and young children with achondroplasia, a population well known to be at risk for a variety of respiratory problems. We also wished to evaluate what, if any, contribution airway malacia makes to the complex respiratory issues that may be present in those with achondroplasia. Retrospective chart review of all infants and young children with achondroplasia who were assessed through the Midwest Regional Bone Dysplasia Clinics from 1985 through 2012 (n = 236) was completed. Records of comprehensive clinical examinations, polysomnographic assessments, and airway visualization were reviewed and abstracted using a data collection form. Analyses were completed comparing the group with and those without evidence for airway malacia. Thirteen of 236 patients (5.5%) were found to have airway malacia. Most of those affected had lower airway involvement (9/13). The presence of airway malacia was correlated with an increased occurrence of obstructive sleep apnea as well as need for oxygen supplementation, airway surgeries and tracheostomy placement. Although estimates of the frequency of airway malacia in the general population are limited, its frequency in children with achondroplasia appears to be much higher than any published general population estimate. The presence of airway malacia appears to confound other breathing abnormalities in this population and results in the need for more invasive airway treatments. © 2013 Wiley Periodicals, Inc.

Difficult Airway Response Team: A Novel Quality Improvement Program for Managing Hospital-Wide Airway Emergencies

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Mark, Lynette J.; Herzer, Kurt R.; Cover, Renee; Pandian, Vinciya; Bhatti, Nasir I.; Berkow, Lauren C.; Haut, Elliott R.; Hillel, Alexander T.; Miller, Christina R.; Feller-Kopman, David J.; Schiavi, Adam J.; Xie, Yanjun J.; Lim, Christine; Holzmueller, Christine; Ahmad, Mueen; Thomas, Pradeep; Flint, Paul W.; Mirski, Marek A.

2015-01-01

or current tracheostomy. Twenty-three patients (6%) required emergent surgical airways. Sixty-two patients (17%) were stabilized and transported to the operating room for definitive airway management. There were no airway management-related deaths, sentinel events, or malpractice claims in adult patients managed by DART. Five in situ simulations conducted in the first program year improved DART's teamwork, communication, and response times and increased the functionality of the difficult airway carts. Over the 5-year period, we conducted 18 airway courses, through which more than 200 providers were trained. Conclusions DART is a comprehensive program for improving difficult airway management. Future studies will examine the comparative effectiveness of the DART program and evaluate how DART has impacted patient outcomes, operational efficiency, and costs of care. PMID:26086513

Difficult airway response team: a novel quality improvement program for managing hospital-wide airway emergencies.

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Mark, Lynette J; Herzer, Kurt R; Cover, Renee; Pandian, Vinciya; Bhatti, Nasir I; Berkow, Lauren C; Haut, Elliott R; Hillel, Alexander T; Miller, Christina R; Feller-Kopman, David J; Schiavi, Adam J; Xie, Yanjun J; Lim, Christine; Holzmueller, Christine; Ahmad, Mueen; Thomas, Pradeep; Flint, Paul W; Mirski, Marek A

2015-07-01

-three patients (6%) required emergent surgical airways. Sixty-two patients (17%) were stabilized and transported to the operating room for definitive airway management. There were no airway management-related deaths, sentinel events, or malpractice claims in adult patients managed by DART. Five in situ simulations conducted in the first program year improved DART's teamwork, communication, and response times and increased the functionality of the difficult airway carts. Over the 5-year period, we conducted 18 airway courses, through which >200 providers were trained. DART is a comprehensive program for improving difficult airway management. Future studies will examine the comparative effectiveness of the DART program and evaluate how DART has impacted patient outcomes, operational efficiency, and costs of care.

High-resolution CT of airway reactivity

International Nuclear Information System (INIS)

Herold, C.J.; Brown, R.H.; Hirshman, C.A.; Mitzner, W.; Zerhouni, E.A.

1990-01-01

Assessment of airway reactivity has generally been limited to experimental nonimaging models. This authors of this paper used high-resolution CT (HRCT) to evaluate airway reactivity and to calculate airway resistance (Raw) compared with lung resistance (RL). Ten anesthetized and ventilated dogs were investigated with HRCT (10 contiguous 2-mm sections through the lower lung lobes) during control state, following aerosol histamine challenge, and following posthistamine hyperinflation. The HRCT scans were digitized, and areas of 10 airways per dog (diameter, 1-10 mm) were measured with a computer edging process. Changes in airway area and Raw (calculated by 1/[area] 2 ) were measured. RL was assessed separately, following the same protocol. Data were analyzed by use of a paired t-test with significance at p < .05

Responses of well-differentiated nasal epithelial cells exposed to particles: Role of the epithelium in airway inflammation

International Nuclear Information System (INIS)

Auger, Floriane; Gendron, Marie-Claude; Chamot, Christophe; Marano, Francelyne; Dazy, Anne-Catherine

2006-01-01

Numerous epidemiological studies support the contention that ambient air pollution particles can adversely affect human health. To explain the acute inflammatory process in airways exposed to particles, a number of in vitro studies have been performed on cells grown submerged on plastic and poorly differentiated, and on cell lines, the physiology of which is somewhat different from that of well-differentiated cells. In order to obtain results using a model system in which epithelial cells are similar to those of the human airway in vivo, apical membranes of well-differentiated human nasal epithelial (HNE) cells cultured in an air-liquid interface (ALI) were exposed for 24 h to diesel exhaust particles (DEP) and Paris urban air particles (PM 2.5 ). DEP and PM 2.5 (10-80 μg/cm 2 ) stimulated both IL-8 and amphiregulin (ligand of EGFR) secretion exclusively towards the basal compartment. In contrast, there was no IL-1β secretion and only weak non-reproducible secretion of TNF-α. IL-6 and GM-CSF were consistently stimulated towards the apical compartment and only when cells were exposed to PM 2.5 . ICAM-1 protein expression on cell surfaces remained low after particle exposure, although it increased after TNF-α treatment. Internalization of particles, which is believed to initiate oxidative stress and proinflammatory cytokine expression, was restricted to small nanoparticles (≤ 40 nm). Production of reactive oxygen species (ROS) was detected, and DEP were more efficient than PM 2.5 . Collectively, our results suggest that airway epithelial cells exposed to particles augment the local inflammatory response in the lung but cannot alone initiate a systemic inflammatory response

[Effect of airway humidification on lung injury induced by mechanical ventilation].

Science.gov (United States)

Song, Junjie; Jiang, Min; Qi, Guiyan; Xie, Yuying; Wang, Huaiquan; Tian, Yonggang; Qu, Jingdong; Zhang, Xiaoming; Li, Haibo

2014-12-01

To explore the effect of airway humidification on lung injury as a result of mechanical ventilation with different tidal volume (VT). Twenty-four male Japanese white rabbits were randomly divided into four groups: low VT with airway humidification group, high VT with airway humidification group, low VT and high VT group without humidification, with 6 rabbits in each group. Mechanical ventilation was started after intubation and lasted for 6 hours. Low VT denoted 8 mL/kg, while high VT was 16 mL/kg, fraction of inspired oxygen (FiO₂) denoted 0.40, positive end-expiratory pressure (PEEP) was 0. Temperature at Y piece of circuit in airway humidification groups was monitored and controlled at 40 centigrade. Arterial blood gas analysis, including pH value, arterial partial pressure of oxygen (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂), lung mechanics indexes, including peak airway pressure (P(peak)) and airway resistance (Raw), and lung compliance was measured at 0, 2, 4, 6 hours of mechanical ventilation. The levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in plasma and bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay (ELISA). The animals were sacrificed at the end of mechanical ventilation. The wet to dry (W/D) ratio of lung tissues was calculated. Histopathologic changes in the lung tissueies were observed with microscope, and lung injury score was calculated. Scanning and transmission electron microscopies were used to examine the integrity of the airway cilia and the tracheal epithelium. Compared with low V(T) group, pH value in high V(T) group was significantly increased, PaCO₂was significantly lowered, and no difference in PaO₂was found. P(peak), Raw, and lung compliance were significantly increased during mechanical ventilation. There were no significant differences in blood gas analysis and lung mechanics indexes between low V(T) with airway humidification group and low V

The effect of body weight on distal airway function and airway inflammation.

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van de Kant, Kim D G; Paredi, Paolo; Meah, Sally; Kalsi, Harpal S; Barnes, Peter J; Usmani, Omar S

Obesity is a global health problem that adversely influences the respiratory system. We assessed the effects of body mass index (BMI) on distal airway function and airway inflammation. Impulse oscillometry (IOS) as a measure of distal airway function, together with spirometry, were assessed in adults with a range of different BMIs. Airway inflammation was assessed with the fraction of exhaled nitric oxide (FeNO) and participants exhaled at various exhalation flows to determine alveolar and bronchial NO. In total 34 subjects were enrolled in the study; 19 subjects had a normal BMI (18.50-24.99), whilst 15 subjects were overweight (BMI 25.00-29.99), or obese (BMI ≥30). All subjects had normal spirometry. However, IOS measures of airway resistance (R) at 5Hz, 20Hz and frequency dependence (R 5-20 ) were elevated in overweight/obese individuals, compared to subjects with a normal BMI (median (interquartile range)); 5Hz: 0.41 (0.37, 0.45) vs. 0.32 (0.30, 0.37)kPa/l/s; 20Hz: 0.34 (0.30, 0.37) vs. 0.30 (0.26, 0.33)kPa/l/s; R 5-20 : 0.06 (0.04, 0.11) vs. 0.03 (0.01, 0.05)kPa/l/s; plimitation) and FeNO inflammatory measures, did not differ between groups (p>0.05). Being overweight has significant effects on distal and central airway function as determined by IOS, which is not detected by spirometry. Obesity does not influence airway inflammation as measured by FeNO. IOS is a reliable technique to identify airway abnormalities in the presence of normal spirometry in overweight people. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Direct numerical simulation of particle laden flow in a human airway bifurcation model

International Nuclear Information System (INIS)

Stylianou, Fotos S.; Sznitman, Josué; Kassinos, Stavros C.

2016-01-01

laminar and turbulent conditions. Given the suspected role of external mechanical stress on the airway epithelium in determining mucus clearance and chronic disease development, here we report wall shear stress distributions for both the turbulent and laminar cases. Finally, we also perform Large Eddy Simulations (LES) and Reynolds-Averaged Navier-Stokes (RANS) simulations for the same configuration in order to asses their performance as compared to DNS. We find that LES and RANS perform well and that they are able to capture the key characteristics of the flow field. The agreement between DNS and RANS holds true only for the mean flow field, which is primarily influenced by curvature effects.

Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

Directory of Open Access Journals (Sweden)

Zhuang-Gui Chen

Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

Airway distensibility in Chronic Obstructive Airway Disease

DEFF Research Database (Denmark)

Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

2013-01-01

Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema......-20% (mild), 20%-30% (moderate) or >30% (severe). Spirometry was performed annually and participants were divided into severity groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Data were analysed in a mixed effects regression model with log(airway lumen diameter...... and emphysema, respectively. Conclusions – Airway distensibility decreases significantly with increasing severity of both GOLD status and emphysema, indicating that in COPD the dynamic change in airway calibre during respiration is compromised. Chronic bronchitis and emphysema appear to be interacting...

Functional imaging using computer methods to compare the effect of salbutamol and ipratropium bromide in patient-specific airway models of COPD

Directory of Open Access Journals (Sweden)

De Backer LA

2011-11-01

Full Text Available LA De Backer1, WG Vos2, R Salgado3, JW De Backer2, A Devolder1, SL Verhulst1, R Claes1, PR Germonpré1, WA De Backer11Department of Respiratory Medicine, 2FluidDA, 3Department of Radiology, Antwerp University Hospital, Antwerp, BelgiumBackground: Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD. However, their bronchodilating effect has not yet been compared in the central and distal airways. Functional imaging using computational fluid dynamics offers the possibility of making such a comparison. The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways.Methods: Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments. Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging. Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography.Results: Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product. On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways. Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient. Salbutamol was more effective in the other patients.Conclusion: This pilot study gives an innovative insight into the modes of

Videolaryngoscopy versus Fiber-optic Intubation through a Supraglottic Airway in Children with a Difficult Airway: An Analysis from the Multicenter Pediatric Difficult Intubation Registry.

Science.gov (United States)

Burjek, Nicholas E; Nishisaki, Akira; Fiadjoe, John E; Adams, H Daniel; Peeples, Kenneth N; Raman, Vidya T; Olomu, Patrick N; Kovatsis, Pete G; Jagannathan, Narasimhan; Hunyady, Agnes; Bosenberg, Adrian; Tham, See; Low, Daniel; Hopkins, Paul; Glover, Chris; Olutoye, Olutoyin; Szmuk, Peter; McCloskey, John; Dalesio, Nicholas; Koka, Rahul; Greenberg, Robert; Watkins, Scott; Patel, Vikram; Reynolds, Paul; Matuszczak, Maria; Jain, Ranu; Khalil, Samia; Polaner, David; Zieg, Jennifer; Szolnoki, Judit; Sathyamoorthy, Kumar; Taicher, Brad; Riveros Perez, N Ricardo; Bhattacharya, Solmaletha; Bhalla, Tarun; Stricker, Paul; Lockman, Justin; Galvez, Jorge; Rehman, Mohamed; Von Ungern-Sternberg, Britta; Sommerfield, David; Soneru, Codruta; Chiao, Franklin; Richtsfeld, Martina; Belani, Kumar; Sarmiento, Lina; Mireles, Sam; Bilen Rosas, Guelay; Park, Raymond; Peyton, James

2017-09-01

The success rates and related complications of various techniques for intubation in children with difficult airways remain unknown. The primary aim of this study is to compare the success rates of fiber-optic intubation via supraglottic airway to videolaryngoscopy in children with difficult airways. Our secondary aim is to compare the complication rates of these techniques. Observational data were collected from 14 sites after management of difficult pediatric airways. Patient age, intubation technique, success per attempt, use of continuous ventilation, and complications were recorded for each case. First-attempt success and complications were compared in subjects managed with fiber-optic intubation via supraglottic airway and videolaryngoscopy. Fiber-optic intubation via supraglottic airway and videolaryngoscopy had similar first-attempt success rates (67 of 114, 59% vs. 404 of 786, 51%; odds ratio 1.35; 95% CI, 0.91 to 2.00; P = 0.16). In subjects less than 1 yr old, fiber-optic intubation via supraglottic airway was more successful on the first attempt than videolaryngoscopy (19 of 35, 54% vs. 79 of 220, 36%; odds ratio, 2.12; 95% CI, 1.04 to 4.31; P = 0.042). Complication rates were similar in the two groups (20 vs. 13%; P = 0.096). The incidence of hypoxemia was lower when continuous ventilation through the supraglottic airway was used throughout the fiber-optic intubation attempt. In this nonrandomized study, first-attempt success rates were similar for fiber-optic intubation via supraglottic airway and videolaryngoscopy. Fiber-optic intubation via supraglottic airway is associated with higher first-attempt success than videolaryngoscopy in infants with difficult airways. Continuous ventilation through the supraglottic airway during fiber-optic intubation attempts may lower the incidence of hypoxemia.

Members of Bitter Taste Receptor Cluster Tas2r143/Tas2r135/Tas2r126 Are Expressed in the Epithelium of Murine Airways and Other Non-gustatory Tissues

Directory of Open Access Journals (Sweden)

Shuya Liu

2017-10-01

Full Text Available The mouse bitter taste receptors Tas2r143, Tas2r135, and Tas2r126 are encoded by genes that cluster on chromosome 6 and have been suggested to be expressed under common regulatory elements. Previous studies indicated that the Tas2r143/Tas2r135/Tas2r126 cluster is expressed in the heart, but other organs had not been systematically analyzed. In order to investigate the expression of this bitter taste receptor gene cluster in non-gustatory tissues, we generated a BAC (bacterial artificial chromosome based transgenic mouse line, expressing CreERT2 under the control of the Tas2r143 promoter. After crossing this line with a mouse line expressing EGFP after Cre-mediated recombination, we were able to validate the Tas2r143-CreERT2 transgenic mouse line and monitor the expression of Tas2r143. EGFP-positive cells, indicating expression of members of the cluster, were found in about 47% of taste buds, and could also be found in several other organs. A population of EGFP-positive cells was identified in thymic epithelial cells, in the lamina propria of the intestine and in vascular smooth muscle cells of cardiac blood vessels. EGFP-positive cells were also identified in the epithelium of organs readily exposed to pathogens including lower airways, the gastrointestinal tract, urethra, vagina, and cervix. With respect to the function of cells expressing this bitter taste receptor cluster, RNA-seq analysis in EGFP-positive cells isolated from the epithelium of trachea and stomach showed expression of genes related to innate immunity. These data further support the concept that bitter taste receptors serve functions outside the gustatory system.

Influence of pirfenidone on airway hyperresponsiveness and inflammation in a Brown-Norway rat model of asthma.

Science.gov (United States)

Mansoor, Jim K; Decile, Kendra C; Giri, Shri N; Pinkerton, Kent E; Walby, William F; Bratt, Jennifer M; Grewal, Harinder; Margolin, Solomon B; Schelegle, Edward S

2007-01-01

Pirfenidone was administered to sensitized Brown Norway rats prior to a series of ovalbumin challenges. Airway hyperresponsiveness, inflammatory cell infiltration, mucin and collagen content, and the degree of epithelium and smooth muscle staining for TGF-beta were examined in control, sensitized, and sensitized/challenged rats fed a normal diet or pirfenidone diet. Pirfenidone had no effect on airway hyperresponsiveness, but reduced distal bronchiolar cell infiltration and proximal and distal mucin content. Statistical analysis showed that the control group and sensitized/challenged pirfenidone diet group TGF-beta staining intensity scores were not significantly different from isotype controls, but that the staining intensity scores for the sensitized/challenged normal diet group was significantly different from isotype controls. These results suggest that pirfenidone treatment is effective in reducing some of the components of acute inflammation induced by allergen challenge.

SLOWLY ADAPTING SENSORY UNITS HAVE MORE RECEPTORS IN LARGE AIRWAYS THAN IN SMALL AIRWAYS IN RABBITS

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Jun Liu

2016-12-01

Full Text Available Sensory units of pulmonary slowly adapting receptors (SARs are more active in large airways than in small airways. However, there is no explanation for this phenomenon. Although sensory structures in large airways resemble those in small airways, they are bigger and more complex. Possibly, a larger receptor provides greater surface area for depolarization, and thus has a lower activating threshold and/or a higher sensitivity to stretch, leading to more nerve electrical activities. Recently, a single sensory unit has been reported to contain multiple receptors. Therefore, sensory units in large airways may contain more SARs, which may contribute to high activities. To test this hypothesis, we used a double staining technique to identify sensory receptor sizes. We labeled the sensory structure with Na+/K+-ATPase antibodies and the myelin sheath with myelin basic protein (MBP antibodies. A SAR can be defined as the end formation beyond MBP labeling. Thus, we are able to compare sizes of sensory structures and SARs in large (trachea and bronchi vs small (bronchioles 0.05. However, the sensory structure contains more SARs in large airways than in small airways (9.6±0.6 vs 3.6±0.3; P<0.0001. Thus, our data support the hypothesis that greater numbers of SARs in sensory units of large airways may contribute to higher activities.

Integrated care pathways for airway diseases (AIRWAYS-ICPs)

NARCIS (Netherlands)

Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buhl, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Cepeda Sarabia, A. M.; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; de Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Fink Wagner, A.; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garcés, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzmán, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Lodrup Carlsen, K. C.; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; de Manuel Keenoy, E.; Masjedi, M. R.; Melen, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Momas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Radier Pontal, F.; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schünemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.

2014-01-01

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will

Integrated care pathways for airway diseases (AIRWAYS-ICPs)

NARCIS (Netherlands)

Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buh, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Sarabia, A. M. Cepeda; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; De Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Wagner, A. Fink; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garces, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzman, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Carlsen, K. C. Lodrup; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; Keenoy, E. de Manuel; Masjedi, M. R.; Meten, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Mamas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Pontal, F. Radier; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schunemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; Van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease.

Science.gov (United States)

Martin, J G; Duguet, A; Eidelman, D H

2000-08-01

Airway hyperresponsiveness (AHR), the exaggerated response to constrictor agonists in asthmatic subjects, is incompletely understood. Changes in either the quantity or properties of airway smooth muscle (ASM) are possible explanations for AHR. Morphometric analyses demonstrate structural changes in asthmatic airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy, neovascularization and an increase in ASM mass. Mathematical modelling of airway narrowing suggests that, of all the changes in structure, the increase in ASM mass is the most probable cause of AHR. An increase in ASM mass in the large airways is more closely associated with a greater likelihood of dying from asthma than increases in ASM mass in other locations within the airway tree. ASM contraction is opposed by the elastic recoil of the lungs and airways, which appears to limit the degree of bronchoconstriction in vivo. The cyclical nature of tidal breathing applies stresses to the airway wall that enhance the bronchodilating influence of the lung tissues on the contracting ASM, in all probability by disrupting cross-bridges. However, the increase in ASM mass in asthma may overcome the limitation resulting from the impedances to ASM shortening imposed by the lung parenchyma and airway wall tissues. Additionally, ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a greater degree of bronchoconstriction when stimulated to contract than slower ASM. Changes in ASM properties are induced by the process of sensitization and allergen-exposure such as enhancement of phospholipase C activity and inositol phosphate turnover, and increases in myosin light chain kinase activity. Whether changes in ASM mass or biochemical/biomechanical properties form the basis for asthma remains to be determined.

Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation

DEFF Research Database (Denmark)

Sverrild, Asger; Bergqvist, Anders; Baines, Katherine J

2016-01-01

BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway...... tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. METHODS: Airway hyperresponsiveness to inhaled mannitol was measured in 23 non......-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. RESULTS...

Functional short- and long-term effects of nasal CPAP with and without humidification on the ciliary function of the nasal respiratory epithelium.

Science.gov (United States)

Sommer, J Ulrich; Kraus, Marius; Birk, Richard; Schultz, Johannes D; Hörmann, Karl; Stuck, Boris A

2014-03-01

Continuous positive airway pressure (CPAP) is the gold standard in the treatment of obstructive sleep apnea (OSA), but its impact on ciliary function is unclear to date. Furthermore, CPAP is associated with numerous side effects related to the nose and upper airway. Humidified CPAP is used to relieve these symptoms, but again, little is known regarding its effect on ciliary function of the nasal respiratory epithelium. In this prospective, randomized, crossover trial, 31 patients with OSA (AHI >15/h) were randomized to two treatment arms: nasal continuous positive airway pressure (nCPAP) with humidification or nCPAP without humidification for one night in each modality to assess short-term effects of ciliary beat frequency (CBF) and mucus transport time (MTT) and consecutively for 8 weeks in each modality to assess long-term effects in a crossover fashion. The baseline CBF was 4.8 ± 0.6 Hz, and baseline MTT was 540 ± 221 s. After one night of CPAP with and without humidification, ciliary function increased moderately yet with statistical significance (p humidification did not differ statistically significant. Regarding long-term effects of CPAP, a statistically significant increase in ciliary function above the baseline level and above the short-term level was shown without humidification (7.2 ± 0.4 Hz; 402 ± 176 s; p humidification (9.3 ± 0.7 Hz; 313 ± 95 s; p humidification, nCPAP has moderate effects on short-term ciliary function of the nasal respiratory epithelium. However, a significant increase in ciliary function-both in terms of an increased CBF and a decreased MTT-was detected after long-term use. The effect was more pronounced when humidification was used during nCPAP.

Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and β2-agonist use

Science.gov (United States)

Hastie, Annette T; Wu, Min; Foster, Gayle C; Hawkins, Gregory A; Batra, Vikas; Rybinski, Katherine A; Cirelli, Rosemary; Zangrilli, James G; Peters, Stephen P

2006-01-01

Background Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Methods Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination. Results Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Conclusion Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to β-agonist. The decreased

Alterations in vasodilator-stimulated phosphoprotein (VASP phosphorylation: associations with asthmatic phenotype, airway inflammation and β2-agonist use

Directory of Open Access Journals (Sweden)

Cirelli Rosemary

2006-02-01

Full Text Available Abstract Background Vasodilator-stimulated phosphoprotein (VASP mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1 injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2 regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Methods Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination. Results Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Conclusion Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to �

Randomized crossover comparison of the laryngeal mask airway classic with i-gel laryngeal mask airway in the management of difficult airway in post burn neck contracture patients

Directory of Open Access Journals (Sweden)

Jeevan Singh

2012-01-01

Full Text Available Purpose: The objective of the study was to compare the performance of i-gel supraglottic airway with cLMA in difficult airway management in post burn neck contracture patients and assess the feasibility of i-gel use for emergency airway management in difficult airway situation with reduced neck movement and limited mouth opening. Methods: Prospective, crossover, randomized controlled trial was performed amongst forty eight post burn neck contracture patients with limited mouth opening and neck movement. i-gel and cLMA were placed in random order in each patient. Primary outcome was overall success rate. Other measurements were time to successful ventilation, airway leak pressure, fiberoptic glottic view, visualization of square wave pattern. Results: Success rate for the i-gel was 91.7% versus 79.2% for the cLMA. i-gel required shorter insertion time (19.3 seconds vs. 23.5 seconds, P=0.000. Airway leak pressure difference was statistically significant (i-gel 21.2 cm H20; cLMA 16.9 cm H 2 0; P=0.00. Fiberoptic view through the i-gel showed there were less epiglottic downfolding and better fiberoptic view of the glottis than cLMA. Overall agreement in insertion outcome for i-gel was 22/24 (91.7% successes and 2/24(8.3% failure and for cLMA, 19/24 (79.16% successes and 5/24 (16.7% failure in the first attempt. Conclusion: The i-gel is cheap, effective airway device which is easier to insert and has better clinical performance in the difficult airway management of the airway in the post burn contracture of the neck. Our study shows that i-gel is feasible for emergency airway management in difficult airway situation with reduced neck movement and limited mouth opening in post burn neck.

Airway structure and function in Eisenmenger's syndrome.

Science.gov (United States)

McKay, K O; Johnson, P R; Black, J L; Glanville, A R; Armour, C L

1998-10-01

The responsiveness of airways from patients with Eisenmenger's syndrome (n = 5) was compared with that in airways from organ donors (n = 10). Enhanced contractile responses to cholinergic stimulation were found in airways from patients with Eisenmenger's syndrome. The maximal responses to acetylcholine, carbachol, and parasympathetic nerve stimulation in airway tissue from these patients were 221%, 139%, and 152%, respectively, of the maximal responses obtained in donor tissue. Further, relaxation responses to isoproterenol and levocromakalim were absent (n = 2) or markedly impaired (n = 3) in airways from patients with Eisenmenger's syndrome. This attenuated relaxation response was nonspecific in that it was also absent after vasoactive intestinal peptide, sodium nitroprusside, papaverine, and electrical field application. These observations can most likely be explained by a decrease in intrinsic smooth muscle tone, as precontraction of airways revealed relaxation responses that were equivalent to those obtained in donor tissues. Morphometric analysis of tissues used for the functional studies revealed no differences in the airway dimensions (internal perimeter) or airway wall components (e.g., smooth muscle, cartilage) or total area to explain these observations. Although the mechanism for this observed decrease in intrinsic airway smooth muscle tone is not certain, it may be due to alteration in the substructure of the airway wall or, alternatively, may result from the continued release of depressant factors in the vicinity of the smooth muscle which permanently alters smooth muscle responsiveness.

Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen

International Nuclear Information System (INIS)

Larson, Shawnessy D.; Schelegle, Edward S.; Walby, William F.; Gershwin, Laural J.; Fanuccihi, Michelle V.; Evans, Michael J.; Joad, Jesse P.; Tarkington, Brian K.; Hyde, Dallas M.; Plopper, Charles G.

2004-01-01

Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O 3 ) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O 3 , or HDMA + O 3 for 11 episodes (5 days each, 0.5 ppm O 3 , 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P 3 , while in monkeys exposed to HDMA + O 3 there was a greater significant (P 3 or HDMA + O 3 there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium

Correlative Ultratructural Investigations of Airway Epithelium Following Experimental Exposure to Defined Air Pollutants and Lifestyle Exposure to Tobacco Smoke

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Context: Investigations of cell/molecular level effects of in vivo exposure of airway mucosa of experimental animals to common irritant gases have demonstrated structural and physiological changes reflective of breaches in epithelial barrier function, presence of inflammatory cel...

Comparative Evaluation of the Pharyngeal Airway Space in Unilateral and Bilateral Cleft Lip and Palate Individuals With Noncleft Individuals: A Cone Beam Computed Tomography Study.

Science.gov (United States)

Gandedkar, Narayan H; Chng, Chai Kiat; Basheer, Mohammad Abdul; Chen, Por Yong; Yeow, Vincent Kok Leng

2017-09-01

  To evaluate the pharyngeal airway space changes in complete unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) individuals, and compare with age and sex-matched noncleft (NC) control subjects.   Retrospective study.   Cleft and Craniofacial Centre, KK Women's and Children's Hospital, Singapore.   Twenty UCLP (mean age: 13.4 ± 0.5 years), 18 BCLP (mean age: 13.5 ± 0.5 years) and 20 skeletal Class I subjects (mean age: 13.4 ± 0.6 years) were included in the study. Cone beam computed tomography scans were assessed for pharyngeal airway space (PAS) (oropharyngeal, nasopharyngeal, total airway space volume), and compared with PAS of age and sex-matched skeletal Class I NC individuals.   Pharyngeal airway space showed statistically significant differences in the UCLP, BCLP, and NC control subjects. Oropharyngeal (9338 ± 1108 mm 3 , P space (12 250 ± 1185 mm 3 , P .05).   The pharyngeal airway space was significantly reduced in the BCLP group than were those in UCLP and control groups. This reduced PAS should be taken into account when planning treatment for these individuals.

Humidification and heating of inhaled gas in patients with artificial airway. A narrative review.

Science.gov (United States)

Plotnikow, Gustavo Adrián; Accoce, Matias; Navarro, Emiliano; Tiribelli, Norberto

2018-03-01

Instrumentation of the airways in critical patients (endotracheal tube or tracheostomy cannula) prevents them from performing their function of humidify and heating the inhaled gas. In addition, the administration of cold and dry medical gases and the high flows that patients experience during invasive and non-invasive mechanical ventilation generate an even worse condition. For this reason, a device for gas conditioning is needed, even in short-term treatments, to avoid potential damage to the structure and function of the respiratory epithelium. In the field of intensive therapy, the use of heat and moisture exchangers is common for this purpose, as is the use of active humidification systems. Acquiring knowledge about technical specifications and the advantages and disadvantages of each device is needed for proper use since the conditioning of inspired gases is a key intervention in patients with artificial airway and has become routine care. Incorrect selection or inappropriate configuration of a device can have a negative impact on clinical outcomes. The members of the Capítulo de Kinesiología Intensivista of the Sociedad Argentina de Terapia Intensiva conducted a narrative review aiming to show the available evidence regarding conditioning of inhaled gas in patients with artificial airways, going into detail on concepts related to the working principles of each one.

A new laryngeal mask supraglottic airway device with integrated balloon line: a descriptive and comparative bench study

Directory of Open Access Journals (Sweden)

Zhou YH

2016-11-01

Full Text Available YingHai Zhou,1 Korinne Jew2 1Research & Development, Patient Monitoring & Recovery, Medtronic Technology Center, Shanghai, People’s Republic of China; 2Medical Affairs, Minimally Invasive Therapies Group, Medtronic, Boulder, CO, USA Abstract: Laryngeal masks are invasive devices for airway management placed in the supraglottic position. The Shiley™ laryngeal mask (Shiley™ LM features an integrated inflation tube and airway shaft to facilitate product insertion and reduce the chance of tube occlusion when patients bite down. This study compared the Shiley LM to two other disposable laryngeal mask devices, the Ambu® AuraStraight™ and the LMA Unique™. Overall device design, tensile strength, flexibility of various structures, and sealing performance were measured. The Shiley LM is structurally stronger and its shaft is more resistant to compression than the other devices. The Shiley LM is generally less flexible than the other devices, but this relationship varies with device size. Sealing performance of the devices was similar in a bench assay. The results of this bench study demonstrate that the new Shiley LM resembles other commercially available laryngeal mask devices, though it exhibits greater tensile strength and lower flexibility. Keywords: laryngeal mask, supraglottic airway, supralaryngeal device

A comparison between the v-gel supraglottic airway device and the cuffed endotracheal tube for airway management in spontaneously breathing cats during isoflurane anaesthesia

NARCIS (Netherlands)

van Oostrom, H.; Krauss, M.W.; Sap, R.

2013-01-01

Abstract OBJECTIVE: To compare airway management using the v-gel supraglottic airway device (v-gel SGAD) to that using an endotracheal tube (ETT), with respect to practicability, leakage of volatile anaesthetics and upper airway discomfort in cats. STUDY DESIGN: Prospective, randomized clinical

Progenitor Epithelium

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Marty-Santos, Leilani

2015-01-01

Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

Diagnosis of bronchiectasis and airway wall thickening in children with cystic fibrosis. Objective airway-artery quantification

International Nuclear Information System (INIS)

Kuo, Wieying; Tiddens, Harm A.W.M.; Bruijne, Marleen de; Petersen, Jens; Nasserinejad, Kazem; Ozturk, Hadiye; Chen, Yong; Perez-Rovira, Adria

2017-01-01

To quantify airway and artery (AA)-dimensions in cystic fibrosis (CF) and control patients for objective CT diagnosis of bronchiectasis and airway wall thickness (AWT). Spirometer-guided inspiratory and expiratory CTs of 11 CF and 12 control patients were collected retrospectively. Airway pathways were annotated semi-automatically to reconstruct three-dimensional bronchial trees. All visible AA-pairs were measured perpendicular to the airway axis. Inner, outer and AWT (outer-inner) diameter were divided by the adjacent artery diameter to compute A in A-, A out A- and A WT A-ratios. AA-ratios were predicted using mixed-effects models including disease status, lung volume, gender, height and age as covariates. Demographics did not differ significantly between cohorts. Mean AA-pairs CF: 299 inspiratory; 82 expiratory. Controls: 131 inspiratory; 58 expiratory. All ratios were significantly larger in inspiratory compared to expiratory CTs for both groups (p<0.001). A out A- and A WT A-ratios were larger in CF than in controls, independent of lung volume (p<0.01). Difference of A out A- and A WT A-ratios between patients with CF and controls increased significantly for every following airway generation (p<0.001). Diagnosis of bronchiectasis is highly dependent on lung volume and more reliably diagnosed using outer airway diameter. Difference in bronchiectasis and AWT severity between the two cohorts increased with each airway generation. (orig.)

Rule-based detection of intrathoracic airway trees

International Nuclear Information System (INIS)

Sonka, M.; Park, W.; Hoffman, E.A.

1996-01-01

New sensitive and reliable methods for assessing alterations in regional lung structure and function are critically important for the investigation and treatment of pulmonary diseases. Accurate identification of the airway tree will provide an assessment of airway structure and will provide a means by which multiple volumetric images of the lung at the same lung volume over time can be used to assess regional parenchymal changes. The authors describe a novel rule-based method for the segmentation of airway trees from three-dimensional (3-D) sets of computed tomography (CT) images, and its validation. The presented method takes advantage of a priori anatomical knowledge about pulmonary airway and vascular trees and their interrelationships. The method is based on a combination of 3-D seeded region growing that is used to identify large airways, rule-based two-dimensional (2-D) segmentation of individual CT slices to identify probable locations of smaller diameter airways, and merging of airway regions across the 3-D set of slices resulting in a tree-like airway structure. The method was validated in 40 3-mm-thick CT sections from five data sets of canine lungs scanned via electron beam CT in vivo with lung volume held at a constant pressure. The method's performance was compared with that of the conventional 3-D region growing method. The method substantially outperformed an existing conventional approach to airway tree detection

Randomised comparison of the effectiveness of the laryngeal mask airway supreme, i-gel and current practice in the initial airway management of prehospital cardiac arrest (REVIVE-Airways): a feasibility study research protocol.

Science.gov (United States)

Benger, Jonathan Richard; Voss, Sarah; Coates, David; Greenwood, Rosemary; Nolan, Jerry; Rawstorne, Steven; Rhys, Megan; Thomas, Matthew

2013-01-01

Effective cardiopulmonary resuscitation with appropriate airway management improves outcomes following out-of-hospital cardiac arrest (OHCA). Historically, tracheal intubation has been accepted as the optimal form of OHCA airway management in the UK. The Joint Royal Colleges Ambulance Liaison Committee recently concluded that newer supraglottic airway devices (SADs) are safe and effective devices for hospital procedures and that their use in OHCA should be investigated. This study will address an identified gap in current knowledge by assessing whether it is feasible to use a cluster randomised design to compare SADs with current practice, and also to each other, during OHCA. The primary objective of this study is to assess the feasibility of a cluster randomised trial to compare the ventilation success of two newer SADs: the i-gel and the laryngeal mask airway supreme to usual practice during the initial airway management of OHCA. The secondary objectives are to collect data on ventilation success, further airway interventions required, loss of a previously established airway during transport, airway management on arrival at hospital (or termination of the resuscitation attempt), initial resuscitation success, survival to intensive care admission, survival to hospital discharge and patient outcome at 3 months. Ambulance paramedics will be randomly allocated to one of the three methods of airway management. Adults in medical OHCA attended by a trial paramedic will be eligible for the study. Approval for the study has been obtained from a National Health Service Research Ethics Committee with authority to review proposals for trials of a medical device in incapacitated adults. The results will be made publicly available on an open access website, and we will publish the findings in appropriate journals and present them at national and international conferences relevant to the subject field. ISRCTN: 18528625.

Expression pattern of adhesion molecules in junctional epithelium differs from that in other gingival epithelia.

Science.gov (United States)

Hatakeyama, S; Yaegashi, T; Oikawa, Y; Fujiwara, H; Mikami, T; Takeda, Y; Satoh, M

2006-08-01

The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues, requiring protection from exposure to bacteria and their products. However, of the three epithelia comprising the gingival epithelium, the junctional epithelium has much wider intercellular spaces than the sulcular epithelium and oral gingival epithelium. Hence, the aim of the present study was to characterize the cell adhesion structure in the junctional epithelium compared with the other two epithelia. Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were examined for expression of adhesion molecules by immunofluorescence. In the oral gingival epithelium and sulcular epithelium, but not in the junctional epithelium, desmoglein 1 and 2 in cell-cell contact sites were more abundant in the upper than the suprabasal layers. E-cadherin, the main transmembranous molecule of adherens junctions, was present in spinous layers of the oral gingival epithelium and sulcular epithelium, but was scarce in the junctional epithelium. In contrast, desmoglein 3 and P-cadherin were present in all layers of the junctional epithelium as well as the oral gingival epithelium and sulcular epithelium. Connexin 43 was clearly localized to spinous layers of the oral gingival epithelium, sulcular epithelium and parts of the junctional epithelium. Claudin-1 and occludin were expressed in the cell membranes of a few superficial layers of the oral gingival epithelium. These findings indicated that the junctional epithelium contains only a few desmosomes, composed of only desmoglein 3; adherens junctions are probably absent because of defective E-cadherin. Thus, the anchoring junctions connecting junctional epithelium cells are lax, causing widened intercellular spaces. In contrast, the oral gingival epithelium, which has a few tight junctions, functions as a barrier.

The Tulip GT® airway versus the facemask and Guedel airway: a randomised, controlled, cross-over study by Basic Life Support-trained airway providers in anaesthetised patients.

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Shaikh, A; Robinson, P N; Hasan, M

2016-03-01

We performed a randomised, controlled, cross-over study of lung ventilation by Basic Life Support-trained providers using either the Tulip GT® airway or a facemask with a Guedel airway in 60 anaesthetised patients. Successful ventilation was achieved if the provider produced an end-tidal CO2 > 3.5 kPa and a tidal volume > 250 ml in two of the first three breaths, within 60 sec and within two attempts. Fifty-seven (95%) providers achieved successful ventilation using the Tulip GT compared with 35 (58%) using the facemask (p Basic Life Support-trained airway providers. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

Epithelium percentage estimation facilitates epithelial quantitative protein measurement in tissue specimens.

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Chen, Jing; Toghi Eshghi, Shadi; Bova, George Steven; Li, Qing Kay; Li, Xingde; Zhang, Hui

2013-12-01

The rapid advancement of high-throughput tools for quantitative measurement of proteins has demonstrated the potential for the identification of proteins associated with cancer. However, the quantitative results on cancer tissue specimens are usually confounded by tissue heterogeneity, e.g. regions with cancer usually have significantly higher epithelium content yet lower stromal content. It is therefore necessary to develop a tool to facilitate the interpretation of the results of protein measurements in tissue specimens. Epithelial cell adhesion molecule (EpCAM) and cathepsin L (CTSL) are two epithelial proteins whose expressions in normal and tumorous prostate tissues were confirmed by measuring staining intensity with immunohistochemical staining (IHC). The expressions of these proteins were measured by ELISA in protein extracts from OCT embedded frozen prostate tissues. To eliminate the influence of tissue heterogeneity on epithelial protein quantification measured by ELISA, a color-based segmentation method was developed in-house for estimation of epithelium content using H&E histology slides from the same prostate tissues and the estimated epithelium percentage was used to normalize the ELISA results. The epithelium contents of the same slides were also estimated by a pathologist and used to normalize the ELISA results. The computer based results were compared with the pathologist's reading. We found that both EpCAM and CTSL levels, measured by ELISA assays itself, were greatly affected by epithelium content in the tissue specimens. Without adjusting for epithelium percentage, both EpCAM and CTSL levels appeared significantly higher in tumor tissues than normal tissues with a p value less than 0.001. However, after normalization by the epithelium percentage, ELISA measurements of both EpCAM and CTSL were in agreement with IHC staining results, showing a significant increase only in EpCAM with no difference in CTSL expression in cancer tissues. These results

Histone deacetylase inhibitors up-regulate LL-37 expression independent of toll-like receptor mediated signalling in airway epithelial cells.

Science.gov (United States)

Liu, Quan; Liu, Juan; Roschmann, Kristina Irene Lisolette; van Egmond, Danielle; Golebski, Korneliusz; Fokkens, Wytske Johanna; Wang, Dehui; van Drunen, Cornelis Maria

2013-04-11

HDAC inhibitors have been proposed as anticancer agents. However, their roles in innate genes expression remain not well known. Cathelicidin LL-37 is one of the few human bactericidal peptides, but the regulation of histone acetylation on LL-37 expression in airway epithelium remains largely unknown. Therefore, we investigated the effects of two non-selective HDACi, trichostatin A (TSA) and sodium butyrate (SB), on the expression of the cathelicidin LL-37 in human airway epithelial cells. LL37 in human NCI-H292 airway epithelial cells and the primary cultures of normal nasal epithelial cells(PNEC) in response to HDAC inhibitors with or without poly (I:C) stimulation was assessed using real-time PCR and western blot. In parallel, IL-6 expression was evaluated by ELISA. Our results showed that HDAC inhibitors up-regulated LL-37 gene expression independent of poly (I:C) stimulation in PNEC as well as in NCI-H292 cells. HDAC inhibitors increased LL37 protein expression in NCI-H292 cells but not in PNEC. In addition, HDAC inhibitors significantly inhibited poly (I:C)-induced IL-6 production in both of the epithelial cells. In conclusion, HDAC inhibitors directly up-regulated LL-37 gene expression in human airway epithelial cells.

Bronchoscopic assessment of airway retention time of aerosolized xylitol

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Durairaj, Lakshmi; Neelakantan, Srividya; Launspach, Janice; Watt, Janet L; Allaman, Margaret M; Kearney, William R; Veng-Pedersen, Peter; Zabner, Joseph

2006-01-01

Background Human airway surface liquid (ASL) has abundant antimicrobial peptides whose potency increases as the salt concentration decreases. Xylitol is a 5-carbon sugar that has the ability to lower ASL salt concentration, potentially enhancing innate immunity. Xylitol was detected for 8 hours in the ASL after application in airway epithelium in vitro. We tested the airway retention time of aerosolized iso-osmotic xylitol in healthy volunteers. Methods After a screening spirometry, volunteers received 10 ml of nebulized 5% xylitol. Bronchoscopy was done at 20 minutes (n = 6), 90 minutes (n = 6), and 3 hours (n = 5) after nebulization and ASL was collected using microsampling probes, followed by bronchoalveolar lavage (BAL). Xylitol concentration was measured by nuclear magnetic resonance spectroscopy and corrected for dilution using urea concentration. Results All subjects tolerated nebulization and bronchoscopy well. Mean ASL volume recovered from the probes was 49 ± 23 μl. The mean ASL xylitol concentration at 20, 90, and 180 minutes was 1.6 ± 1.9 μg/μl, 0.6 ± 0.6 μg/μl, and 0.1 ± 0.1 μg/μl, respectively. Corresponding BAL concentration corrected for dilution was consistently lower at all time points. The terminal half-life of aerosolized xylitol obtained by the probes was 45 minutes with a mean residence time of 65 minutes in ASL. Corresponding BAL values were 36 and 50 minutes, respectively. Conclusion After a single dose nebulization, xylitol was detected in ASL for 3 hours, which was shorter than our in vitro measurement. The microsampling probe performed superior to BAL when sampling bronchial ASL. PMID:16483382

Inherent and antigen-induced airway hyperreactivity in NC mice

OpenAIRE

Tetsuto Kobayashi; Toru Miura; Tomoko Haba; Miyuki Sato; Masao Takei; Isao Serizawa

1999-01-01

In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those st...

Diagnosis of bronchiectasis and airway wall thickening in children with cystic fibrosis. Objective airway-artery quantification

Energy Technology Data Exchange (ETDEWEB)

Kuo, Wieying; Tiddens, Harm A.W.M. [Erasmus MC - Sophia Children' s Hospital, Department of Pediatric Pulmonology and Allergology, Rotterdam (Netherlands); Erasmus MC, Department of Radiology, Rotterdam (Netherlands); Bruijne, Marleen de [Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, Rotterdam (Netherlands); University of Copenhagen, Department of Computer Science, Copenhagen (Denmark); Petersen, Jens [University of Copenhagen, Department of Computer Science, Copenhagen (Denmark); Nasserinejad, Kazem [Erasmus MC Cancer Institute, HOVON Data Center, Clinical Trial Center, Rotterdam (Netherlands); Erasmus MC, Department of Biostatistics, Rotterdam (Netherlands); Ozturk, Hadiye [Erasmus MC - Sophia Children' s Hospital, Department of Pediatric Pulmonology and Allergology, Rotterdam (Netherlands); Chen, Yong [General Hospital of Ningxia Medical University, Department of Radiology, Yinchuan (China); Perez-Rovira, Adria [Erasmus MC - Sophia Children' s Hospital, Department of Pediatric Pulmonology and Allergology, Rotterdam (Netherlands); Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, Rotterdam (Netherlands)

2017-11-15

To quantify airway and artery (AA)-dimensions in cystic fibrosis (CF) and control patients for objective CT diagnosis of bronchiectasis and airway wall thickness (AWT). Spirometer-guided inspiratory and expiratory CTs of 11 CF and 12 control patients were collected retrospectively. Airway pathways were annotated semi-automatically to reconstruct three-dimensional bronchial trees. All visible AA-pairs were measured perpendicular to the airway axis. Inner, outer and AWT (outer-inner) diameter were divided by the adjacent artery diameter to compute A{sub in}A-, A{sub out}A- and A{sub WT}A-ratios. AA-ratios were predicted using mixed-effects models including disease status, lung volume, gender, height and age as covariates. Demographics did not differ significantly between cohorts. Mean AA-pairs CF: 299 inspiratory; 82 expiratory. Controls: 131 inspiratory; 58 expiratory. All ratios were significantly larger in inspiratory compared to expiratory CTs for both groups (p<0.001). A{sub out}A- and A{sub WT}A-ratios were larger in CF than in controls, independent of lung volume (p<0.01). Difference of A{sub out}A- and A{sub WT}A-ratios between patients with CF and controls increased significantly for every following airway generation (p<0.001). Diagnosis of bronchiectasis is highly dependent on lung volume and more reliably diagnosed using outer airway diameter. Difference in bronchiectasis and AWT severity between the two cohorts increased with each airway generation. (orig.)

Enhanced airway dilation by positive-pressure inflation of the lungs compared with active deep inspiration in patients with asthma

NARCIS (Netherlands)

Slats, Annelies M.; Janssen, Kirsten; de Jeu, Ronald C.; van der Plas, Dirk T.; Schot, Robert; van den Aardweg, Joost G.; Sterk, Peter J.

2008-01-01

Deep inspiration temporarily reduces induced airways obstruction in healthy subjects. This bronchodilatory effect of deep inspiration is impaired in asthma. Passive machine-assisted lung inflation may augment bronchodilation compared with an active deep inspiration in patients with asthma by either

Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

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Wu, Qun; Jiang, Di; Minor, Maisha; Chu, Hong Wei

2014-01-01

The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection. We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

Directory of Open Access Journals (Sweden)

Qun Wu

Full Text Available The use of electronic cigarettes (e-cigarettes is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV infection.We examined the effects of e-cigarette liquid (e-liquid on pro-inflammatory cytokine (e.g., IL-6 production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1 in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome.

Science.gov (United States)

Reynolds, Susan D; Rios, Cydney; Wesolowska-Andersen, Agata; Zhuang, Yongbin; Pinter, Mary; Happoldt, Carrie; Hill, Cynthia L; Lallier, Scott W; Cosgrove, Gregory P; Solomon, George M; Nichols, David P; Seibold, Max A

2016-09-01

The application of conditional reprogramming culture (CRC) methods to nasal airway epithelial cells would allow more wide-spread incorporation of primary airway epithelial culture models into complex lung disease research. In this study, we adapted the CRC method to nasal airway epithelial cells, investigated the growth advantages afforded by this technique over standard culture methods, and determined the cellular and molecular basis of CRC cell culture effects. We found that the CRC method allowed the production of 7.1 × 10(10) cells after 4 passages, approximately 379 times more cells than were generated by the standard bronchial epithelial growth media (BEGM) method. These nasal airway epithelial cells expressed normal basal cell markers and could be induced to form a mucociliary epithelium. Progenitor cell frequency was significantly higher using the CRC method in comparison to the standard culture method, and progenitor cell maintenance was dependent on addition of the Rho-kinase inhibitor Y-27632. Whole-transcriptome sequencing analysis demonstrated widespread gene expression changes in Y-27632-treated basal cells. We found that Y-27632 treatment altered expression of genes fundamental to the formation of the basal cell cytoskeleton, cell-cell junctions, and cell-extracellular matrix (ECM) interactions. Importantly, we found that Y-27632 treatment up-regulated expression of unique basal cell intermediate filament and desmosomal genes. Conversely, Y-27632 down-regulated multiple families of protease/antiprotease genes involved in ECM remodeling. We conclude that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification.

Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen.

Science.gov (United States)

Larson, Shawnessy D; Schelegle, Edward S; Walby, William F; Gershwin, Laural J; Fanuccihi, Michelle V; Evans, Michael J; Joad, Jesse P; Tarkington, Brian K; Hyde, Dallas M; Plopper, Charles G

2004-02-01

Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O(3)) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O(3), or HDMA + O(3) for 11 episodes (5 days each, 0.5 ppm O(3), 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P < 0.05) decrements in the density of epithelial nerves in monkeys exposed to HDMA or O(3), while in monkeys exposed to HDMA + O(3) there was a greater significant (P < 0.05) reduction in epithelial innervation. In animals exposed to O(3) or HDMA + O(3) there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium.

Comparison of the air-Q intubating laryngeal airway and the cobra perilaryngeal airway as conduits for fiber optic-guided intubation in pediatric patients.

Science.gov (United States)

Girgis, Karim K; Youssef, Maha M I; ElZayyat, Nashwa S

2014-10-01

One of the methods proposed in cases of difficult airway management in children is using a supraglottic airway device as a conduit for tracheal intubation. The aim of this study was to compare the efficacy of the Air-Q Intubating Laryngeal Airway (Air-Q) and the Cobra Perilaryngeal Airway (CobraPLA) to function as a conduit for fiber optic-guided tracheal intubation in pediatric patients. A total of 60 children with ages ranging from 1 to 6 years, undergoing elective surgery, were randomized to have their airway managed with either an Air-Q or CobraPLA. Outcomes recorded were the success rate, time and number of attempts required for fiber optic-guided intubation and the time required for device removal after intubation. We also recorded airway leak pressure (ALP), fiber optic grade of glottic view and occurrence of complications. Both devices were successfully inserted in all patients. The intubation success rate was comparable with the Air-Q and the CobraPLA (96.7% vs. 90%), as was the first attempt success rate (90% vs. 80%). The intubation time was significantly longer with the CobraPLA (29.5 ± 10.9 s vs. 23.2 ± 9.8 s; P fiber optic grade of glottic view was comparable with the two devices. The CobraPLA was associated with a significantly higher incidence of blood staining of the device on removal and post-operative sore throat. Both the Air-Q and CobraPLA can be used effectively as a conduit for fiber optic-guided tracheal intubation in children. However, the Air-Q proved to be superior due to a shorter intubation time and less airway morbidity compared with the CobraPLA.

Upper airway gene expression in smokers: the mouth as a "window to the soul" of lung carcinogenesis?

Science.gov (United States)

Spira, Avrum

2010-03-01

This perspective on Boyle et al. (beginning on page 266 in this issue of the journal) explores transcriptomic profiling of upper airway epithelium as a biomarker of host response to tobacco smoke exposure. Boyle et al. have shown a striking relationship between smoking-related gene expression changes in the mouth and bronchus. This relationship suggests that buccal gene expression may serve as a relatively noninvasive surrogate marker of the physiologic response of the lung to tobacco smoke that could be used in large-scale screening and chemoprevention studies for lung cancer.

Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents

Energy Technology Data Exchange (ETDEWEB)

Zaccone, Eric J. [Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV (United States); Goldsmith, W. Travis [Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV (United States); Shimko, Michael J. [Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV (United States); Wells, J.R.; Schwegler-Berry, Diane; Willard, Patsy A.; Case, Shannon L.; Thompson, Janet A. [Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV (United States); Fedan, Jeffrey S. [Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV (United States); Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV (United States)

2015-12-15

Inhalation of butter flavoring by workers in the microwave popcorn industry may result in “popcorn workers' lung.” In previous in vivo studies rats exposed for 6 h to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance, we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity. We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 h to diacetyl or 2,3-pentanedione vapors (25 or ≥ 60 ppm) and the effects on short circuit current and transepithelial resistance (R{sub t}) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na{sup +} transport, without affecting Cl{sup −} transport or Na{sup +},K{sup +}-pump activity. R{sub t} was unaffected. Na{sup +} transport recovered 18 h after exposure. Concentrations (100–360 ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 h post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro. - Highlights: • Butter flavoring vapor effects on human cultured airway epithelium were studied. • Na transport was reduced by a 6-h exposure to 25 ppm diacetyl and 2,3-pentanedione. • Na transport recovered 18 h after exposure. • > 60 ppm transepithelial voltage and resistance were abolished; cells were damaged. • Cells metabolized diacetyl and 2,3-pentanedione

Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents

International Nuclear Information System (INIS)

Zaccone, Eric J.; Goldsmith, W. Travis; Shimko, Michael J.; Wells, J.R.; Schwegler-Berry, Diane; Willard, Patsy A.; Case, Shannon L.; Thompson, Janet A.; Fedan, Jeffrey S.

2015-01-01

Inhalation of butter flavoring by workers in the microwave popcorn industry may result in “popcorn workers' lung.” In previous in vivo studies rats exposed for 6 h to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance, we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity. We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 h to diacetyl or 2,3-pentanedione vapors (25 or ≥ 60 ppm) and the effects on short circuit current and transepithelial resistance (R t ) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na + transport, without affecting Cl − transport or Na + ,K + -pump activity. R t was unaffected. Na + transport recovered 18 h after exposure. Concentrations (100–360 ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 h post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro. - Highlights: • Butter flavoring vapor effects on human cultured airway epithelium were studied. • Na transport was reduced by a 6-h exposure to 25 ppm diacetyl and 2,3-pentanedione. • Na transport recovered 18 h after exposure. • > 60 ppm transepithelial voltage and resistance were abolished; cells were damaged. • Cells metabolized diacetyl and 2,3-pentanedione into acetoin and 2-OH-3-pentanone.

Clearance of lead-212 ions from rabbit bronchial epithelium to blood

International Nuclear Information System (INIS)

James, A.C.; Greenhalgh, J.R.; Smith, H.

1977-01-01

The absorption of 212 Pb ions from bronchial epithelium to blood has been investigated in anaesthetized rabbits. The 212 Pb ions were introduced by intubation either into the trachea or into smaller, more distal bronchi. Removal from lung was followed by external γ-counting. Mucociliary clearance to the GI tract was blocked by tracheostomy. Two distinct phases of clearance from bronchial epithelium to blood were observed. Approximately 20% of deposited 212 Pb was rapidly absorbed with a half-time of about 4 min, the remainder with a biological half-time of about 9 h, irrespective of the site of instillation in the bronchial tree. Two hours after deposition, the 212 Pb remaining in lung was found to be partitioned between mucus and the bronchial epithelium, with a substantial but minor fraction in the epithelium. Uptake of 212 Pb in the skeleton was estimated to be about 20% of the 212 Pb entering the blood circulation. Removal by the kidneys, at 25%, was comparable with skeletal uptake. These results are compared with previously published work using rodents, dogs and man which demonstrated either rapid or slow absorption but not both phases occurring together. (author)

Randomised trial of elective continuous positive airway pressure (CPAP) compared with rescue CPAP after extubation

OpenAIRE

Robertson, N; Hamilton, P

1998-01-01

AIM—To determine if a weaning regimen on flow driver continuous positive airway pressure (CPAP) would decrease the number of ventilator days but increase the number of CPAP days when compared with a rescue regimen.
METHODS—Fifty eight babies of 24-32 weeks gestation with respiratory distress syndrome (RDS) were studied prospectively. After extubation they were randomly allocated to receive CPAP for 72 hours (n=29) according to a weaning regimen, or were placed in headbox ...

The Structure of Urethral Epithelium in Merinos Lambs

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Vasile RUS

2018-05-01

Full Text Available The aim of this study was to investigate by histological techniques the structure of urethral epithelium in lambs. In this study, we harvested several fragments (prostatic, membranous and cavernous from urethra from 5 merino’s lambs of 3 months old. The first anatomical segment, the prostatic urethra, is lined by a urinary epithelium. The intermediary layer of this epithelium is formed of 5-6 rows of oval cells. The second segment of urethra has the same type of epithelium but the intermediary layer is formed of 6-7 rows of oval cells. In the last anatomical segment, the penile urethra, the epithelium is the same, but the intermediary layer has 3-4 rows of oval cells. In lambs, the urethra is lined by urinary epithelium. The urethral epithelium does not have the same thickness in all segments. The thinner epithelium it is in the cavernous urethra, the ticker is the membranous urethra.

Airway stents

Science.gov (United States)

Keyes, Colleen

2018-01-01

Stents and tubes to maintain the patency of the airways are commonly used for malignant obstruction and are occasionally employed in benign disease. Malignant airway obstruction usually results from direct involvement of bronchogenic carcinoma, or by extension of carcinomas occurring in the esophagus or the thyroid. External compression from lymph nodes or metastatic disease from other organs can also cause central airway obstruction. Most malignant airway lesions are surgically inoperable due to advanced disease stage and require multimodality palliation, including stent placement. As with any other medical device, stents have significantly evolved over the last 50 years and deserve an in-depth understanding of their true capabilities and complications. Not every silicone stent is created equal and the same holds for metallic stents. Herein, we present an overview of the topic as well as some of the more practical and controversial issues surrounding airway stents. We also try to dispel the myths surrounding stent removal and their supposed use only in central airways. At the end, we come to the long-held conclusion that stents should not be used as first line treatment of choice, but after ruling out the possibility of curative surgical resection or repair. PMID:29707506

Radioaerosol lung imaging in small airways disease

Energy Technology Data Exchange (ETDEWEB)

Weiss, T; Dorow, P; Felix, R

1981-06-01

Aerosol inhalation lung imaging was performed in 35 asymptomatic smokers who have been selected on the basis of abnormal findings in small airways pulmonary function tests. Qualitative (image inspection) and quantitative (aerosol distribution index = ADI) analysis of the radioaerosol lung patterns was accomplished. Compared to healthy subjects as well as to patients with chronic obstructive lung disease significant differences of mean aerosol distribution homogeneity were observed. A characteristic type of abnormal aerosol pattern, indicating peripheral airways obstruction, was found in 71% of the patients with small airways disease.

Garlic ameliorates histological changes in the uterine epithelium of lead induced mice

International Nuclear Information System (INIS)

Waseem, N.; Butt, S.A.; Hamid, S.

2015-01-01

To evaluate the protective role of garlic extract on the histology of the uterine epithelium exposed to lead acetate in an animal model. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College in collaboration with National Institute of health from April to June 2013. Material and Methods: Thirty female BALBc mice were selected. Ten animals were placed in each group. Group A being the control was given normal diet. Group B was given lead acetate at a dose of 30 mg/kg/day. Group C was given lead acetate 30 mg/kg/day and garlic extract 500 mg/kg/day through oral gavage tube for 60 days. Animals were sacrificed and dissected at the end of 60 days. Right uterine horn was processed, embedded and stained for histological study. Height of epithelium was measured. It was taken from apical to basal end of the cells. Results: There was increase in height of the lining epithelium of uterus in group B, mean value 19.70 ± 4.81 meu m when compared to Group A, with mean value 13.25 ± 2.37 meu m. The height of the epithelium was relatively reduced in group C, with mean value 14.50 ± 2.30 meu m when compared with group B. In group C results were same as Group A. The p values were 0.001 when group A was compared to group B, 0.688 when group A was compared to group C and 0.005 when group B was compared to group C. Conclusion: The height of epithelium was markedly increased in lead acetate treated group which returned to normal when co treated with garlic extract. Hence garlic ameliorated the changes induced by lead. (author)

Dilemmas, Confusion, and Misconceptions Related to Small Airways Directed Therapy

DEFF Research Database (Denmark)

Lavorini, Federico; Pedersen, Søren; Usmani, Omar S.

2017-01-01

During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innova......During the past decade, there has been increasing evidence that the small airways (ie, airways COPD. The increased interest in small airways is, at least in part, a result...... of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure...... benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas...

Differential proteiomic analysis of mouse intestinal epithelium irradiated by γ-ray

International Nuclear Information System (INIS)

Zhang Bo; Su Yongping; Liu Xiaohong; Ai Guoping; Ran Xinze; Wei Yongjiang; Wang Junping; Cheng Tianmin

2003-01-01

Objective: For elucidating the molecular mechanism of reconstruction of intestinal epithelium damaged by ionizing radiation, the proteomes of murine intestinal epithelium from normal and irradiated mice were compared by 2-D electrophoresis. Methods: Histopathologic sections of whole small intestine made from BALB/c mice 3 h and 72 h after total-body irradiation were stained with hematoxylin-eosin. Intestinal epithelial cells were isolated from normal and irradiated mice. The total protein samples prepared by one-step method were used in 2-D electrophoresis, the protein maps were compared and the differential spots were detected with PDQuest analysis software. Twenty-eight different spots were cut off from the gels, digested in gel with trypsin, measured with MALDI-TOF-MS and searched in database. Results: Small intestinal epithelium was damaged as early as 3 h after irradiation, and reconstructed 72 h later. After Coomassie-staining, the 2-DE image analysis by PDQuest software detected 638 ± 39 protein spots in normal mice group, 566 ± 32 spots in 3 hours post irradiation group, and 591 ± 29 spots in 3 days post irradiation group. The 2-DE images showed that proteomes of intestinal epithelium were altered with γ-irradiation. The proteins identified by peptide mass fingerprinting involved in cellular events, including signal transduction, metabolism and oxidative stress responses. Conclusions: Gamma-irradiation can induce the protein expression of intestinal epithelium. The technique of 2-D electrophoresis is a useful tool in the study of molecular mechanism of radiation damage

Dynamics of Bovine Sperm Interaction with Epithelium Differ Between Oviductal Isthmus and Ampulla1

Science.gov (United States)

Ardon, Florencia; Markello, Ross D.; Hu, Lian; Deutsch, Zarah I.; Tung, Chih-Kuan; Wu, Mingming; Suarez, Susan S.

2016-01-01

In mammals, many sperm that reach the oviduct are held in a reservoir by binding to epithelium. To leave the reservoir, sperm detach from the epithelium; however, they may bind and detach again as they ascend into the ampulla toward oocytes. In order to elucidate the nature of binding interactions along the oviduct, we compared the effects of bursts of strong fluid flow (as would be caused by oviductal contractions), heparin, and hyperactivation on detachment of bovine sperm bound in vitro to epithelium on intact folds of isthmic and ampullar mucosa. Intact folds of oviductal mucosa were used to represent the strong attachments of epithelial cells to each other and to underlying connective tissue that exist in vivo. Effects of heparin on binding were tested because heparin binds to the Binder of SPerm (BSP) proteins that attach sperm to oviductal epithelium. Sperm bound by their heads to beating cilia on both isthmic and ampullar epithelia and could not be detached by strong bursts of fluid flow. Addition of heparin immediately detached sperm from isthmic epithelium but not ampullar epithelium. Addition of 4-aminopyridine immediately stimulated hyperactivation of sperm but did not detach them from isthmic or ampullar epithelium unless added with heparin. These observations indicate that the nature of binding of sperm to ampullar epithelium differs from that of binding to isthmic epithelium; specifically, sperm bound to isthmic epithelium can be detached by heparin alone, while sperm bound to ampullar epithelium requires both heparin and hyperactivation to detach from the epithelium. PMID:27605344

Humidification and heating of inhaled gas in patients with artificial airway. A narrative review

Science.gov (United States)

Plotnikow, Gustavo Adrián; Accoce, Matias; Navarro, Emiliano; Tiribelli, Norberto

2018-01-01

Instrumentation of the airways in critical patients (endotracheal tube or tracheostomy cannula) prevents them from performing their function of humidify and heating the inhaled gas. In addition, the administration of cold and dry medical gases and the high flows that patients experience during invasive and non-invasive mechanical ventilation generate an even worse condition. For this reason, a device for gas conditioning is needed, even in short-term treatments, to avoid potential damage to the structure and function of the respiratory epithelium. In the field of intensive therapy, the use of heat and moisture exchangers is common for this purpose, as is the use of active humidification systems. Acquiring knowledge about technical specifications and the advantages and disadvantages of each device is needed for proper use since the conditioning of inspired gases is a key intervention in patients with artificial airway and has become routine care. Incorrect selection or inappropriate configuration of a device can have a negative impact on clinical outcomes. The members of the Capítulo de Kinesiología Intensivista of the Sociedad Argentina de Terapia Intensiva conducted a narrative review aiming to show the available evidence regarding conditioning of inhaled gas in patients with artificial airways, going into detail on concepts related to the working principles of each one. PMID:29742220

Effects of concentrated ambient particles on normal and hypersecretory airways in rats.

Science.gov (United States)

Harkema, Jack R; Keeler, Gerald; Wagner, James; Morishita, Masako; Timm, Edward; Hotchkiss, Jon; Marsik, Frank; Dvonch, Timothy; Kaminski, Norbert; Barr, Edward

2004-08-01

Epidemiological studies have reported that elevated levels of particulate air pollution in urban communities are associated with increases in attacks of asthma based on evidence from hospital admissions and emergency department visits. Principal pathologic features of chronic airway diseases, like asthma, are airway inflammation and mucous hypersecretion with excessive amounts of luminal mucus and increased numbers of mucus-secreting cells in regions of the respiratory tract that normally have few or no mucous cells (ie, mucous cell metaplasia). The overall goal of the present project was to understand the adverse effects of urban air fine particulate matter (PM2.5; pollutants in the outdoor air of a local Detroit community with a high incidence of childhood asthma; (2) determine the effects of this community-based PM2.5 on the airway epithelium in normal rats and rats compromised with preexisting hypersecretory airway diseases (ie, animal models of human allergic airway disease--asthma and chronic bronchitis); and (3) identify the chemical or physical components of PM2.5 that are responsible for PM2.5 -induced airway inflammation and epithelial alterations in these animal models. Two animal models of airway disease were used to examine the effects of PM2.5 exposure on preexisting hypersecretory airways: neutrophilic airway inflammation induced by endotoxin challenge in F344 rats and eosinophilic airway inflammation induced by ovalbumin (OVA) challenge in BN rats. A mobile air monitoring and exposure laboratory equipped with inhalation exposure chambers for animal toxicology studies, air pollution monitors, and particulate collection devices was used in this investigation. The mobile laboratory was parked in a community in southwestern Detroit during the summer months when particulate air pollution is usually high (July and September 2000). We monitored the outdoor air pollution in this community daily, and exposed normal and compromised rats to concentrated PM2

Incidence of unanticipated difficult airway using an objective airway score versus a standard clinical airway assessment

DEFF Research Database (Denmark)

Nørskov, Anders Kehlet; Rosenstock, Charlotte Valentin; Wetterslev, Jørn

2013-01-01

-specific assessment. Data from patients' pre-operative airway assessment are registered in the Danish Anaesthesia Database. Objective scores for intubation and mask ventilation grade the severity of airway managements. The accuracy of predicting difficult intubation and mask ventilation is measured for each group...... the examination and registration of predictors for difficult mask ventilation with a non-specified clinical airway assessment on prediction of difficult mask ventilation.Method/Design: We cluster-randomized 28 Danish departments of anaesthesia to airway assessment either by the SARI or by usual non...... that registration of the SARI and predictors for difficult mask ventilation are mandatory for the intervention group but invisible to controls....

Magnetic resonance imaging of the pediatric airway

International Nuclear Information System (INIS)

Auringer, S.T.; Bisset, G.S. III; Myer, C.M.

1991-01-01

Evaluation of the pediatric airway is often complex and may require multiple imaging techniques and invasive procedures. We performed magnetic resonance (MR) imaging of the airway in 34 children with clinical evidence of chronic airway obstruction and compared MR findings with those obtained by surgery and/or endoscopy. MR diagnoses included vascular compression in 15 patients, primary tracheomalacic states in 12 patients, and mediastinal masses in 4 patients. Findings were normal for 3 patients. The MR findings were in agreement with the endoscopic findings in 25 to 28 cases and in agreement with the surgical findings in 21 to 21 cases. (orig./GDG)

Higher order optical aberrations and visual acuity in a randomized controlled trial comparing transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus

Directory of Open Access Journals (Sweden)

Godefrooij DA

2017-10-01

Full Text Available Daniel A Godefrooij, Mustapha El Kandoussi, Nienke Soeters, Robert PL Wisse Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands Purpose: The purpose of this study was to compare the effects of transepithelial crosslinking (trans-CXL versus epithelium-off crosslinking (epi-off CXL for progressive keratoconus with respect to the development of higher order aberrations (HOAs and their effects on visual acuity.Materials and methods: A total of 61 patients were randomized and examined preoperatively and 1, 3, 6, and 12 months postoperatively in an academic referral center. Total corneal HOAs were compared between the two treatment groups using mixed linear modeling. Types of HOAs (coma, trefoil, and spherical aberration that differed between groups were entered in a multivariable analysis to test their effect on uncorrected distance visual acuity (UDVA and corrected distance visual acuity (CDVA.Results: The epi-off CXL group had more flattening in maximal keratometry compared to the trans-CXL group (P=0.02. UDVA did not differ significantly between the groups (P=0.59; however, CDVA was significantly more improved in the trans-CXL group (P=0.02. Horizontal trefoil improved more in the epi-off group compared to the trans-CXL group (P=0.04, whereas the other HOAs were virtually unchanged in both groups. Differences in changes in HOAs between the two groups had no effect on either UCVA (P=0.76 or CDVA (P=0.96.Conclusion: Although HOAs are clinically relevant determinants of vision quality in keratoconus patients, the change in total HOAs post treatment did not differ between the trans-CXL and epi-off CXL groups. Only horizontal trefoil differed significantly post treatment between the trans-CXL and epi-off CXL groups. However, this difference did not independently affect either UDVA or CDVA. Trans-CXL provides no benefit over epi-off CXL regarding visual relevant HOAs. Keywords

The disruption of the epithelial mesenchymal trophic unit in COPD.

Science.gov (United States)

Behzad, Ali R; McDonough, John E; Seyednejad, Nazgol; Hogg, James C; Walker, David C

2009-12-01

Progression of COPD is associated with a measurable increase in small airway wall thickness resulting from a repair and remodeling process that involves fibroblasts of the epithelial mesenchymal trophic unit (EMTU). The present study was designed to examine the organization of fibroblasts within the lamina propria of small airways with respect to their contacts with the epithelium and with each other in persons with COPD. Transmission electron microcopy (TEM) and three-dimensional (3D) reconstructions of serial TEM sections were used to estimate the frequency and determine the nature of the contacts between the epithelium and fibroblasts within the EMTU in small airways from 5 controls (smokers with normal lung function), from 6 persons with mild (GOLD-1) and 5 with moderate (GOLD-2) COPD. In airways from control lungs fibroblasts make frequent contact with cytoplasmic extensions of epithelial cells through apertures in the epithelial basal lamina, but the frequency of these fibroblast-epithelial contacts is reduced in both mild and moderate COPD compared to controls (p < 0.01). The 3D reconstructions showed that the cytoplasmic extensions of lamina propria fibroblasts form a reticulum with fibroblast-fibroblast contacts in an airway from a control subject but this reticulum may be reorganized in airways of COPD patients. Development of COPD is associated with significant disruption of the EMTU due to a reduction of contacts between fibroblasts and the epithelium.

Effects of using the simplified airway risk index vs usual airway assessment on unanticipated difficult tracheal intubation - a cluster randomized trial with 64,273 participants

DEFF Research Database (Denmark)

Nørskov, A K; Wetterslev, J; Rosenstock, C V

2016-01-01

departments vs 1.00% (302) in Non-SARI departments. Adjusted OR was 1.26 (0.68-2.34). CONCLUSIONS: Using the SARI compared with usual airway assessment we detected no statistical significant changes in unanticipated difficult- or easy intubations. CLINICAL TRIAL REGISTRATION: NCT01718561.......BACKGROUND: Unanticipated difficult intubation remains a challenge in anaesthesia. The Simplified Airway Risk Index (SARI) is a multivariable risk model consisting of seven independent risk factors for difficult intubation. Our aim was to compare preoperative airway assessment based on the SARI...

Methylene-tetrahydrofolate reductase contributes to allergic airway disease.

Directory of Open Access Journals (Sweden)

Kenneth R Eyring

Full Text Available Environmental exposures strongly influence the development and progression of asthma. We have previously demonstrated that mice exposed to a diet enriched with methyl donors during vulnerable periods of fetal development can enhance the heritable risk of allergic airway disease through epigenetic changes. There is conflicting evidence on the role of folate (one of the primary methyl donors in modifying allergic airway disease.We hypothesized that blocking folate metabolism through the loss of methylene-tetrahydrofolate reductase (Mthfr activity would reduce the allergic airway disease phenotype through epigenetic mechanisms.Allergic airway disease was induced in C57BL/6 and C57BL/6Mthfr-/- mice through house dust mite (HDM exposure. Airway inflammation and airway hyperresponsiveness (AHR were measured between the two groups. Gene expression and methylation profiles were generated for whole lung tissue. Disease and molecular outcomes were evaluated in C57BL/6 and C57BL/6Mthfr-/- mice supplemented with betaine.Loss of Mthfr alters single carbon metabolite levels in the lung and serum including elevated homocysteine and cystathionine and reduced methionine. HDM-treated C57BL/6Mthfr-/- mice demonstrated significantly less airway hyperreactivity (AHR compared to HDM-treated C57BL/6 mice. Furthermore, HDM-treated C57BL/6Mthfr-/- mice compared to HDM-treated C57BL/6 mice have reduced whole lung lavage (WLL cellularity, eosinophilia, and Il-4/Il-5 cytokine concentrations. Betaine supplementation reversed parts of the HDM-induced allergic airway disease that are modified by Mthfr loss. 737 genes are differentially expressed and 146 regions are differentially methylated in lung tissue from HDM-treated C57BL/6Mthfr-/- mice and HDM-treated C57BL/6 mice. Additionally, analysis of methylation/expression relationships identified 503 significant correlations.Collectively, these findings indicate that the loss of folate as a methyl donor is a modifier of

Challenges and opportunities for tissue-engineering polarized epithelium.

Science.gov (United States)

Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

2014-02-01

The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

Conditional inactivation of p53 in mouse ovarian surface epithelium does not alter MIS driven Smad2-dominant negative epithelium-lined inclusion cysts or teratomas.

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Suzanne M Quartuccio

Full Text Available Epithelial ovarian cancer is the most lethal gynecological malignancy among US women. The etiology of this disease, although poorly understood, may involve the ovarian surface epithelium or the epithelium of the fallopian tube fimbriae as the progenitor cell. Disruptions in the transforming growth factor beta (TGFβ pathway and p53 are frequently found in chemotherapy-resistant serous ovarian tumors. Transgenic mice expressing a dominant negative form of Smad2 (Smad2DN, a downstream transcription factor of the TGFβ signaling pathway, targeted to tissues of the reproductive tract were created on a FVB background. These mice developed epithelium-lined inclusion cysts, a potential precursor lesion to ovarian cancer, which morphologically resembled oviductal epithelium but exhibited protein expression more closely resembling the ovarian surface epithelium. An additional genetic "hit" of p53 deletion was predicted to result in ovarian tumors. Tissue specific deletion of p53 in the ovaries and oviducts alone was attempted through intrabursal or intraoviductal injection of Cre-recombinase expressing adenovirus (AdCreGFP into p53 (flox/flox mice. Ovarian bursal cysts were detected in some mice 6 months after intrabursal injection. No pathological abnormalities were detected in mice with intraoviductal injections, which may be related to decreased infectivity of the oviductal epithelium with adenovirus as compared to the ovarian surface epithelium. Bitransgenic mice, expressing both the Smad2DN transgene and p53 (flox/flox, were then exposed to AdCreGFP in the bursa and oviductal lumen. These mice did not develop any additional phenotypes. Exposure to AdCreGFP is not an effective methodology for conditional deletion of floxed genes in oviductal epithelium and tissue specific promoters should be employed in future mouse models of the disease. In addition, a novel phenotype was observed in mice with high expression of the Smad2DN transgene as validated

New frontiers in CT imaging of airway disease

International Nuclear Information System (INIS)

Grenier, Philippe A.; Beigelman-Aubry, Catherine; Fetita, Catalin; Preteux, Francoise; Brauner, Michel W.; Lenoir, Stephane

2002-01-01

Combining helical volumetric CT acquisition and thin-slice thickness during breath hold provides an accurate assessment of both focal and diffuse airway diseases. With multiple detector rows, compared with single-slice helical CT, multislice CT can cover a greater volume, during a simple breath hold, and with better longitudinal and in-plane spatial resolution and improved temporal resolution. The result in data set allows the generation of superior multiplanar and 3D images of the airways, including those obtained from techniques developed specifically for airway imaging, such as virtual bronchography and virtual bronchoscopy. Complementary CT evaluation at suspended or continuous full expiration is mandatory to detect air trapping that is a key finding for depicting an obstruction on the small airways. Indications for CT evaluation of the airways include: (a) detection of endobronchial lesions in patients with an unexplained hemoptysis; (b) evaluation of extent of tracheobronchial stenosis for planning treatment and follow-up; (c) detection of congenital airway anomalies revealed by hemoptysis or recurrent infection; (d) detection of postinfectious or postoperative airway fistula or dehiscence; and (e) diagnosis and assessment of extent of bronchiectasis and small airway disease. Improvement in image analysis technique and the use of spirometrically control of lung volume acquisition have made possible accurate and reproducible quantitative assessment of airway wall and lumen areas and lung density. This contributes to better insights in physiopathology of obstructive lung disease, particularly in chronic obstructive pulmonary disease and asthma. (orig.)

Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma?

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Sulaiman, S. A.

2017-01-01

Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO) is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma. PMID:28660089

Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma?

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N. A. Kamalaldin

2017-01-01

Full Text Available Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma.

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

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Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Powell, Karen S. [Research Resource Facilities, University of Louisville, Louisville, KY (United States); Roberts, Andrew M. [Department of Physiology, University of Louisville, Louisville, KY (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

2017-01-15

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed. �

A novel method for pulmonary research: Assessment of bioenergetic function at the air–liquid interface

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Weiling Xu

2014-01-01

Full Text Available Air–liquid interface cell culture is an organotypic model for study of differentiated functional airway epithelium in vitro. Dysregulation of cellular energy metabolism and mitochondrial function have been suggested to contribute to airway diseases. However, there is currently no established method to determine oxygen consumption and glycolysis in airway epithelium in air–liquid interface. In order to study metabolism in differentiated airway epithelial cells, we engineered an insert for the Seahorse XF24 Analyzer that enabled the measure of respiration by oxygen consumption rate (OCR and glycolysis by extracellular acidification rate (ECAR. Oxidative metabolism and glycolysis in airway epithelial cells cultured on the inserts were successfully measured. The inserts did not affect the measures of OCR or ECAR. Cells under media with apical and basolateral feeding had less oxidative metabolism as compared to cells on the inserts at air-interface with basolateral feeding. The design of inserts that can be used in the measure of bioenergetics in small numbers of cells in an organotypic state may be useful for evaluation of new drugs and metabolic mechanisms that underlie airway diseases.

Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness

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O'Connor George T

2011-07-01

Full Text Available Abstract Background Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (Rmin is abnormally elevated in subjects with airway hyperresponsiveness. Methods The Rmin was measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. Rmin and spirometric indices were measured before and after bronchodilation (albuterol and bronchoconstriction (methacholine. A preliminary study of 84 healthy subjects first established height dependence of baseline Rmin values. Results Asthmatics had a higher baseline Rmin % predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004. Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline Rmin was able to identify subjects with airway hyperresponsiveness (PC20 min % predicted, FEV1 % predicted, and FEF25-75 % predicted, respectively. Also, 80% of the subjects with baseline Rmin min > 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic. Conclusions These findings suggest that baseline Rmin, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline Rmin to asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, Rmin could provide a clinically useful tool for assessing asthma and monitoring response to treatment.

Reinstatement of "germinal epithelium" of the ovary

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Nishida Naoyo

2006-08-01

Full Text Available Abstract Background The existing dogma that the former term ovarian "germinal epithelium" resulted from a mistaken belief that it could give rise to new germ cells is now strongly challenged. Discussion Two years ago, a research group of the University of Tennessee led by Antonin Bukovsky successfully demonstrated the oogenic process from the human ovarian covering epithelium now commonly called the ovarian surface epithelium. They showed the new oocyte with zona pellucida and granulosa cells, both originated from the surface epithelium arising from mesenchymal cells in the tunica albuginea, and stressed that the human ovary could form primary follicles throughout the reproductive period. This gives a big impact not only to the field of reproductive medicine, but also to the oncologic area. The surface epithelium is regarded as the major source of ovarian cancers, and most of the neoplasms exhibit the histology resembling müllerian epithelia. Since the differentiating capability of the surface epithelium has now expanded, the histologic range of the neoplasms in this category may extend to include both germ cell tumors and sex cord-stromal cell tumors. Summary Since the oogenic capability of ovarian surface cells has been proven, it is now believed that the oocytes can originate from them. The term "germinal epithelium", hence, might reasonably be reinstated.

Different alpha crystallin expression in human age-related and congenital cataract lens epithelium.

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Yang, Jing; Zhou, Sheng; Guo, Minfei; Li, Yuting; Gu, Jianjun

2016-05-28

The purpose of this study was to investigate the different expressions of αA-crystallin and αB-crystallin in human lens epithelium of age-related and congenital cataracts. The central part of the human anterior lens capsule approximately 5 mm in diameter together with the adhering epithelial cells, were harvested and processed within 6 hours after cataract surgery from age-related and congenital cataract patients or from normal eyes of fresh cadavers. The mRNA and soluble protein levels of αA-crystallin and αB-crystallin in the human lens epithelium were detected by real-time PCR and western blots, respectively. The mRNA and soluble protein expressions of αA-crystallin and αB-crystallin in the lens epithelium were both reduced in age-related and congenital cataract groups when compared with the normal control group. However, the degree of α-crystallin loss in the lens epithelium was highly correlated with different cataract types. The α-crystallin expression of the lens epithelium was greatly reduced in the congenital cataract group but only moderately decreased in the age-related cataract group. The reduction of αA-crystallin soluble protein levels in the congenital cataract group was approximately 2.4 fold decrease compared with that of the age-related cataract group, while an mRNA fold change of 1.67 decrease was observed for the age-related cataract group. Similarly, the reduction of soluble protein levels of αB-crystallin in the congenital cataract group was approximately a 1.57 fold change compared with that of the age-related cataract group. A 1.75 fold change for mRNA levels compared with that of the age-related cataract group was observed. The results suggest that the differential loss of α-crystallin in the human lens epithelium could be associated with the different mechanisms of cataractogenesis in age-related versus congenital cataracts, subsequently resulting in different clinical presentations.

Orofacial-cervical alterations in individuals with upper airway resistance syndrome

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Pedro Wey Barbosa de Oliveira

Full Text Available ABSTRACT INTRODUCTION: Studies that assess the upper airways in sleep-related breathing disorders have been performed only in patients with obstructive sleep apnea syndrome who seek medical attention. Therefore, in addition to the need for population studies, there are no data on the orofacial-cervical physical examination in subjects with upper airway resistance syndrome. OBJECTIVES: To compare the orofacial-cervical examination between volunteers with upper airway resistance syndrome and without sleep-related breathing disorders. METHODS: Through questionnaires, physical measurements, polysomnography, and otorhinolaryngological evaluation, this study compared the orofacial-cervical physical examination, through a systematic analysis of the facial skeleton, mouth, throat, and nose, between volunteers with upper airway resistance syndrome and volunteers without sleep-related breathing disorders in a representative sample of the adult population of the city of São Paulo. RESULTS: There were 1042 volunteers evaluated; 49 subjects (5% were excluded as they did not undergo otorhinolaryngological evaluation, 381 (36% had apnea-hypopnea index > 5 events/hour, and 131 (13% had oxyhemoglobin saturation < 90%. Among the remaining 481 subjects (46%, 30 (3% met the criteria for the upper airway resistance syndrome definition and 53 (5% met the control group criteria. At the clinical evaluation of nasal symptoms, the upper airway resistance syndrome group had more oropharyngeal dryness (17% vs. 29.6%; p = 0.025 and septal deviation grades 1-3 (49.1% vs. 57.7%; p = 0.025 when compared to controls. In the logistic regression model, it was found that individuals from the upper airway resistance syndrome group had 15.6-fold higher chance of having nose alterations, 11.2-fold higher chance of being hypertensive, and 7.6-fold higher chance of complaining of oropharyngeal dryness when compared to the control group. CONCLUSION: Systematic evaluation of the facial

Sleep apnea is associated with bronchial inflammation and continuous positive airway pressure-induced airway hyperresponsiveness.

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Devouassoux, Gilles; Lévy, Patrick; Rossini, Eliane; Pin, Isabelle; Fior-Gozlan, Michèle; Henry, Mireille; Seigneurin, Daniel; Pépin, Jean-Louis

2007-03-01

Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated. The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa. The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP. Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% +/- 20% vs 43% +/- 12%, P Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use. Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.

Transport across the choroid plexus epithelium

DEFF Research Database (Denmark)

Praetorius, Jeppe; Damkier, Helle Hasager

2017-01-01

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus...... is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature......, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1) the choroid plexus epithelium as the source of mediators necessary for central nervous system...

Differential effects of allergen challenge on large and small airway reactivity in mice.

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Chantal Donovan

Full Text Available The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways disease to induce inflammation and remodelling and determine whether in vivo hyperresponsiveness to methacholine is consistent with in vitro reactivity of trachea and small airways. Balb/C mice were sensitised (days 0, 14 and challenged (3 times/week, 6 weeks with ovalbumin. Airway reactivity was compared with saline-challenged controls in vivo assessing whole lung resistance, and in vitro measuring the force of tracheal contraction and the magnitude/rate of small airway narrowing within lung slices. Increased airway inflammation, epithelial remodelling and fibrosis were evident following allergen challenge. In vivo hyperresponsiveness to methacholine was maintained in isolated trachea. In contrast, methacholine induced slower narrowing, with reduced potency in small airways compared to controls. In vitro incubation with IL-1/TNFα did not alter reactivity. The hyporesponsiveness to methacholine in small airways within lung slices following chronic ovalbumin challenge was unexpected, given hyperresponsiveness to the same agonist both in vivo and in vitro in tracheal preparations. This finding may reflect the altered interactions of small airways with surrounding parenchymal tissue after allergen challenge to oppose airway narrowing and closure.

Airway somatosensory deficits and dysphagia in Parkinson's disease.

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Hammer, Michael J; Murphy, Caitlin A; Abrams, Trisha M

2013-01-01

Individuals with Parkinson's disease (PD) often experience substantial impairment of swallow control, and are typically unaware of the presence or severity of their impairments suggesting that these individuals may also experience airway sensory deficits. However, the degree to which impaired swallow function in PD may relate to airway sensory deficits has yet to be formally tested. The purpose of this study was to examine whether airway sensory function is associated with swallow impairment in PD. Eighteen PD participants and 18 healthy controls participated in this study and underwent endoscopic assessment of airway somatosensory function, endoscopic assessment of swallow function, and clinical ratings of swallow and disease severity. PD participants exhibited abnormal airway somatosensory function and greater swallow impairment compared with healthy controls. Swallow and sensory deficits in PD were correlated with disease severity. Moreover, PD participants reported similar self-rated swallow function as healthy controls, and swallow deficits were correlated with sensory function suggesting an association between impaired sensory function and poor self-awareness of swallow deficits in PD. These results suggest that control of swallow is influenced by airway somatosensory function, that swallow-related deficits in PD are related to abnormal somatosensation, and that swallow and airway sensory function may degrade as a function of disease severity. Therefore, the basal ganglia and related neural networks may play an important role to integrate airway sensory input for swallow-related motor control. Furthermore, the airway deficits observed in PD suggest a disintegration of swallow-related sensory and motor control.

Airway Science curriculum demonstration project : summary of initial evaluation findings.

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1988-10-01

The performance, perceptions, and characteristics of Airway Science hires were compared with those of traditional hires. As of May 12, 1987. a total of 197 Airway Science candidates had been selected into FAA occupations. The demographic characterist...

Adam8 Limits the Development of Allergic Airway Inflammation in Mice

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Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

2013-01-01

To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

Airway Clearance Techniques (ACTs)

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Full Text Available ... Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. ... or caregiver. Older kids and adults can choose ACTs that they can do on their own. Share ...

Assessment of airway lesion in obstructive lung diseases by CT

International Nuclear Information System (INIS)

Niimi, Akio; Matsumoto, Hisako; Ueda, Tetsuya; Mishima, Michiaki

2002-01-01

Airway lesion in obstructive pulmonary diseases, such as asthma or chronic obstructive pulmonary disease (COPD), has recently been assessed quantitatively. Especially in asthma, wall thickening of central airways, and its relation to the severity of disease or airflow obstruction has been clarified. Pathophysiologic importance of peripheral airway lesion has also been highlighted by pathologic or physiologic studies. However, direct evaluation of peripheral airway lesion is beyond resolutional limitation of CT. To assess airway trapping, an indirect CT finding of peripheral airway disease, by quantitative and semiquantitative measures and compare them with clinical indices such as pulmonary function, airway responsiveness, or airway inflammation. Patients with stable asthma (n=20) were studied. HRCT at 3 levels of both lungs were scanned. Low attenuation area (LAA)% and mean lung density were quantitatively assessed by an automatic method. Distribution of mosaic pattern was visually scored semiquantitatively. LAA% and mean lung density at full expiratory phase correlated with the degree of airflow obstruction. Mosaic score at full inspiratory phase correlated with the severity of disease and airflow obstruction. Expiratory/inspiratory ratio of mean lung density was also associated with airway responsiveness or residual volume/total lung capacity (RV/TLC). These CT findings may be useful as markers of asthma pathophysiology. (author)

Airway Clearance Techniques (ACTs)

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Full Text Available ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ... Offer their tips for fitting ACTs into daily life Airway Clearance Techniques | Webcast ... Facebook Twitter ...

Efficacy of Surgical Airway Plasty for Benign Airway Stenosis.

Science.gov (United States)

Tsukioka, Takuma; Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Inoue, Hidetoshi; Yamamoto, Ryoji

2016-01-01

Long-term patency is required during treatment for benign airway stenosis. This study investigated the effectiveness of surgical airway plasty for benign airway stenosis. Clinical courses of 20 patients, who were treated with surgical plasty for their benign airway stenosis, were retrospectively investigated. Causes of stenosis were tracheobronchial tuberculosis in 12 patients, post-intubation stenosis in five patients, malacia in two patients, and others in one patient. 28 interventional pulmonology procedures and 20 surgical plasty were performed. Five patients with post-intubation stenosis and four patients with tuberculous stenosis were treated with tracheoplasty. Eight patients with tuberculous stenosis were treated with bronchoplasty, and two patients with malacia were treated with stabilization of the membranous portion. Anastomotic stenosis was observed in four patients, and one to four additional treatments were required. Performance status, Hugh-Jones classification, and ventilatory functions were improved after surgical plasty. Outcomes were fair in patients with tuberculous stenosis and malacia. However, efficacy of surgical plasty for post-intubation stenosis was not observed. Surgical airway plasty may be an acceptable treatment for tuberculous stenosis. Patients with malacia recover well after surgical plasty. There may be untreated patients with malacia who have the potential to benefit from surgical plasty.

Measurement of lung airways in three dimensions using hyperpolarized helium-3 MRI

International Nuclear Information System (INIS)

Peterson, Eric T; Fain, Sean B; Dai Jionghan; Holmes, James H

2011-01-01

Large airway measurement is clinically important in cases of airway disease and trauma. The gold standard is computed tomography (CT), which allows for airway measurement. However, the ionizing radiation dose associated with CT is a major limitation in longitudinal studies and trauma. To avoid ionizing radiation from CT, we present a method for measuring the large airway diameter in humans using hyperpolarized helium-3 (HPHe) MRI in conjunction with a dynamic 3D radial acquisition. An algorithm is introduced which utilizes the significant airway contrast for semi-automated segmentation and skeletonization which is used to derive the airway lumen diameter. The HPHe MRI method was validated with quantitative CT in an excised and desiccated porcine lung (linear regression R 2 = 0.974 and slope = 0.966 over 32 airway segments). The airway lumen diameters were then compared in 24 human subjects (22 asthmatics and 2 normals; linear regression R 2 value of 0.799 and slope = 0.768 over 309 airway segments). The feasibility for airway path analysis to areas of ventilation defect is also demonstrated.

Interventions designed using quality improvement methods reduce the incidence of serious airway events and airway cardiac arrests during pediatric anesthesia.

Science.gov (United States)

Spaeth, James P; Kreeger, Renee; Varughese, Anna M; Wittkugel, Eric

2016-02-01

Although serious complications during pediatric anesthesia are less common than they were 20 years ago, serious airway events continue to occur. Based on Quality Improvement (QI) data from our institution, a QI project was designed to reduce the incidence of serious airway events and airway cardiac arrests. A quality improvement team consisting of members of the Department of Anesthesia was formed and QI data from previous years were analyzed. The QI team developed a Smart Aim, Key Driver Diagram, and specific Interventions that focused on the accessibility of emergency drugs, the use of nondepolarizing muscle relaxants for endotracheal intubation in children 2 years and younger, and the presence of anesthesia providers until emergence from anesthesia in high-risk patients. The percentage of cases where muscle relaxants were utilized in children 2 years and younger for endotracheal intubation and where atropine and succinylcholine were readily available increased at both our base and outpatient facilities. Over the 2.5-year study period, the incidence of serious airway events and airway cardiac arrests was reduced by 44% and 59%, respectively compared to the previous 2-year period. We utilized QI methodology to design and implement a project which led to greater standardization of clinical practice within a large pediatric anesthesia group. Based on an understanding of system issues impacting our clinical practice, we designed and tested interventions that led to a significant reduction in the incidence of serious airway events and airway cardiac arrests. © 2015 John Wiley & Sons Ltd.

Expression of semaphorin 3A in the rat corneal epithelium during wound healing

International Nuclear Information System (INIS)

Morishige, Naoyuki; Ko, Ji-Ae; Morita, Yukiko; Nishida, Teruo

2010-01-01

The neural guidance protein semaphorin 3A (Sema3A) is expressed in corneal epithelial cells of the adult rat. We have now further investigated the localization of Sema3A in the normal rat corneal epithelium as well as changes in its expression pattern during wound healing after central corneal epithelial debridement. The expression pattern of Sema3A was compared with that of the tight-junction protein zonula occludens-1 (ZO-1), the gap-junction protein connexin43 (Cx43), or the cell proliferation marker Ki67. Immunofluorescence analysis revealed that Sema3A was present predominantly in the membrane of basal and wing cells of the intact corneal epithelium. The expression of Sema3A at the basal side of basal cells was increased in the peripheral epithelium compared with that in the central region. Sema3A was detected in all layers at the leading edge of the migrating corneal epithelium at 6 h after central epithelial debridement. The expression of Sema3A was markedly up-regulated in the basal and lateral membranes of columnar basal cells apparent in the thickened, newly healed epithelium at 1 day after debridement, but it had largely returned to the normal pattern at 3 days after debridement. The expression of ZO-1 was restricted to superficial epithelial cells and remained mostly unchanged during the wound healing process. The expression of Cx43 in basal cells was down-regulated at the leading edge of the migrating epithelium but was stable in the remaining portion of the epithelium. Ki67 was not detected in basal cells of the central epithelium at 1 day after epithelial debridement, when Sema3A was prominently expressed. Immunoblot analysis showed that the abundance of Sema3A in the central cornea was increased 1 day after epithelial debridement, whereas that of ZO-1 or Cx43 remained largely unchanged. This increase in Sema3A expression was accompanied by up-regulation of the Sema3A coreceptor neuropilin-1. Our observations have thus shown that the expression of

A randomized non-crossover study comparing the ProSeal and Classic laryngeal mask airway in anaesthetized children.

Science.gov (United States)

Lopez-Gil, M; Brimacombe, J; Garcia, G

2005-12-01

We tested the hypothesis that ease of insertion, oropharyngeal leak pressure, fibreoptic position, gastric insufflation, and the frequency of mucosal trauma differ between the ProSeal laryngeal mask airway (PLMA) and the classic laryngeal mask airway (cLMA) in anaesthetized children. For the PLMA, we also assessed the ease of gastric tube placement via the PLMA drain tube and measure residual gastric volume. 240 consecutive ASA I-III children aged 1-16 yr were randomized for airway management with the ProSeal or cLMA. The time taken to provide an effective airway, the number of insertion attempts, fibreoptic position of the airway tube and frequency of mucosal trauma were similar, but oropharyngeal leak pressure was higher (33 vs 26 cm H(2)O, Ptube insertion was successful at the first attempt in 106 of 120, and at the second attempt in 14 of 120. The mean (sd; range) value for residual gastric volume was 2.2 (5.9; 0-30) ml. There were no differences in performance among sizes for the PLMA and the cLMA. We conclude that ease of insertion, fibreoptic position, and frequency of mucosal trauma are similar for the PLMA and cLMA in children, but oropharyngeal leak pressure is higher and gastric insufflation less common for the PLMA. Gastric tube insertion has a high success rate, provided the PLMA is correctly positioned.

Carbohydrate determinants in ferret conjunctiva are affected by infection with influenza H1N1 virus

DEFF Research Database (Denmark)

Kirkeby, Svend; Martel, Cyril; Aasted, Bent

2013-01-01

Carbohydrates often accomplish as cell-surface receptors for microorganisms and influenza virus preferentially binds to sialic acid through the viral haemagglutinin. The virus may attach not only to the epithelium in the airways, but also to the surface ocular epithelium.......Carbohydrates often accomplish as cell-surface receptors for microorganisms and influenza virus preferentially binds to sialic acid through the viral haemagglutinin. The virus may attach not only to the epithelium in the airways, but also to the surface ocular epithelium....

Measurement of the thickness of the bronchial epithelium

International Nuclear Information System (INIS)

Bowden, D.H.; Baldwin, F.

1989-02-01

Cancer of the lung in uranium miners is thought to be related to the inhalation of gaseous radon daughters which become attached to molecules of water vapour or to dust particles. Since, the depth of tissue penetration by alpha particles is short, the thickness of the epithelium that lines the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the present study were: 1) to measure the thickness of human bronchial epithelium; 2) to determine the distribution and depth of the nuclei of basal cells in the bronchial epithelium; and 3) to compare these parameters in groups of smokers and non-smokers. Twenty-nine surgically removed specimens of the lung were examined (26 smokers, 3 non-smokers). The specimens were fixed and prepared for examination by light and electron microscopy. Blocks of tissue were oriented so that the maximum number of bronchi were cut in cross-section; measurements included bronchi of all sizes from bronchial generations (1≥ 9.01 mm) diameter to the smallest bronchioles, generations 7 - 16 (0.26 - 2.0 mm). Comparison of measurements in smokers and non-smokers show no significant differences, so that the 29 cases are considered to represent a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness. Of more importance are the figures relating to the distance from the cell surface to the underlying nucleus. Here too, with the exception of goblet cells, the measurements are significantly smaller in generations 7 - 16 than in generation 1

Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls

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Ishikawa N

2015-01-01

Full Text Available Nobuhisa Ishikawa,1 Noboru Hattori,2 Nobuoki Kohno,2 Akihiro Kobayashi,3 Tomoyuki Hayamizu,4 Malcolm Johnson5 1Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan; 2Department of Molecular and Internal Medicine, Hiroshima University, Hiroshima, Japan; 3Biomedical Data Science Department, 4Medical Affairs Respiratory Department, GlaxoSmithKline Shibuya-ku, Tokyo, Japan; 5Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UK Purpose: To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups.Patients and methods: This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures.Results: The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8, surfactant protein D (SP-D, and Krebs von den Lungen 6 (KL-6 in sputum and clara cell 16 (CC-16, high-sensitivity C-reactive protein (hs-CRP, and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001, neutrophils and MMP-9 (P<0.001, macrophages and KL-6 (P<0.01, total cell count and IL-8 (P<0.05, neutrophils and IL-8 (P<0.05, and macrophages and MMP-9 (P<0.05. Significant correlations were also

Extraglottic airway devices: technology update

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Sharma B

2017-08-01

Full Text Available Bimla Sharma, Chand Sahai, Jayashree Sood Department of Anaesthesiology, Pain and Perioperative Medicine, Sir Ganga Ram Hospital, New Delhi, India Abstract: Extraglottic airway devices (EADs have revolutionized the field of airway management. The invention of the laryngeal mask airway was a game changer, and since then, there have been several innovations to improve the EADs in design, functionality, safety and construction material. These have ranged from changes in the shape of the mask, number of cuffs and material used, like rubber, polyvinylchloride and latex. Phthalates, which were added to the construction material in order to increase device flexibility, were later omitted when this chemical was found to have serious adverse reproductive outcomes. The various designs brought out by numerous companies manufacturing EADs resulted in the addition of several devices to the airway market. These airway devices were put to use, many of them with inadequate or no evidence base regarding their efficacy and safety. To reduce the possibility of compromising the safety of the patient, the Difficult Airway Society (DAS formed the Airway Device Evaluation Project Team (ADEPT to strengthen the evidence base for airway equipment and vet the new extraglottic devices. A preuse careful analysis of the design and structure may help in better understanding of the functionality of a particular device. In the meantime, the search for the ideal EAD continues. Keywords: extraglottic airway devices, laryngeal mask airway, other extraglottic airway devices, safety, technology update

Airway management in neuroanesthesiology.

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Aziz, Michael

2012-06-01

Airway management for neuroanesthesiology brings together some key principles that are shared throughout neuroanesthesiology. This article appropriately targets the cervical spine with associated injury and the challenges surrounding airway management. The primary focus of this article is on the unique airway management obstacles encountered with cervical spine injury or cervical spine surgery, and unique considerations regarding functional neurosurgery are addressed. Furthermore, topics related to difficult airway management for those with rheumatoid arthritis or pituitary surgery are reviewed. Copyright © 2012 Elsevier Inc. All rights reserved.

Imaging of mucus clearance in the airways of living spontaneously breathing mice by optical coherence microscopy (Conference Presentation)

Science.gov (United States)

Pieper, Mario; Schulz-Hildebrandt, Hinnerk; Hüttmann, Gereon; König, Peter

2016-03-01

Mucus transport is essential to remove inhaled particles and pathogens from the lung. Impaired removal of mucus often results in worsening of lung diseases. To understand the mechanisms of mucus transport and to monitor the impact of therapeutic strategies, it is essential to visualize airways and mucus in living animals without disturbing transport processes by intubation or surgically opening the airways. We developed a custom-built optical coherence microscope (OCM) providing a lateral and axial resolution of approximately 1.5 µm with a field of view of 2 mm at up to 150 images/s. Images of the intact trachea and its mucus transport were recorded in anesthetized spontaneously breathing mice. NaCl solution (0.9% and 7%) or Lipopolysaccharide were applied intranasally. OCM resolved detailed structure of the trachea and enabled measuring the airway surface liquid (ASL) thickness through the tracheal wall. Without stimulation, the amount of ASL was only a few µm above the epithelium and remained constant. After intranasal application of 30 µl saline at different concentrations, an early fast cough-like fluid removal with velocities higher than 1 mm/s was observed that removed a high amount of liquid. The ASL thickness increased transiently and quickly returned to levels before stimulation. In contrast to saline, application of Lipopolysaccharide induced substantial mucus release and an additional slow mucus transport by ciliary beating (around 100 µm/s) towards the larynx was observed. In conclusion, OCM is appropriate unique tool to study mechanisms of mucus transport in the airways and effects of therapeutic interventions in living animals.

Upper Airway Volume Segmentation Analysis Using Cine MRI Findings in Children with Tracheostomy Tubes

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Fricke, Bradley L.; Abbott, M. Bret; Donnelly, Lane F.; Dardzinski, Bernard J.; Poe, Stacy A.; Kalra, Maninder; Amin, Raouf S.; Cotton, Robin T. [Cincinnati Children' s Hospital Medical Center, Cincinnati (United States)

2007-12-15

The purpose of this study is to evaluate the airway dynamics of the upper airway as depicted on cine MRI in children with tracheotomy tubes during two states of airflow through the upper airway. Sagittal fast gradient echo cine MR images of the supra-glottic airway were obtained with a 1.5T MRI scanner on seven children with tracheotomy tubes. Two sets of images were obtained with either the tubes capped or uncapped. The findings of the cine MRI were retrospectively reviewed. Volume segmentation of the cine images to compare the airway volume change over time (mean volume, standard deviation, normalized range, and coefficient of variance) was performed for the capped and uncapped tubes in both the nasopharynx and hypopharynx (Signed Rank Test). Graphical representation of the airway volume over time demonstrates a qualitative increased fluctuation in patients with the tracheotomy tube capped as compared to uncapped in both the nasopharyngeal and hypopharyngeal regions of interest. In the nasopharynx, the mean airway volume (capped 2.72 mL, uncapped 2.09 mL, p = 0.0313), the airway volume standard deviation (capped 0.42 mL, uncapped 0.20 mL, p = 0.0156), and the airway volume range (capped 2.10 mL, uncapped 1.09 mL, p = 0.0156) were significantly larger in the capped group of patients. In the hypopharynx, the airway volume standard deviation (capped 1.54 mL, uncapped 0.67 mL, p = 0.0156), and the airway volume range (capped 6.44 mL, uncapped 2.93 mL, p = 0.0156) were significantly larger in the capped tubes. The coefficient of variance (capped 0.37, uncapped 0.26, p = 0.0469) and the normalized range (capped 1.52, uncapped 1.09, p = 0.0313) were significantly larger in the capped tubes. There is a statistically significant change in airway dynamics in children with tracheotomy tubes when breathing via the airway as compared to breathing via the tracheotomy tube.

Upper Airway Volume Segmentation Analysis Using Cine MRI Findings in Children with Tracheostomy Tubes

International Nuclear Information System (INIS)

Fricke, Bradley L.; Abbott, M. Bret; Donnelly, Lane F.; Dardzinski, Bernard J.; Poe, Stacy A.; Kalra, Maninder; Amin, Raouf S.; Cotton, Robin T.

2007-01-01

The purpose of this study is to evaluate the airway dynamics of the upper airway as depicted on cine MRI in children with tracheotomy tubes during two states of airflow through the upper airway. Sagittal fast gradient echo cine MR images of the supra-glottic airway were obtained with a 1.5T MRI scanner on seven children with tracheotomy tubes. Two sets of images were obtained with either the tubes capped or uncapped. The findings of the cine MRI were retrospectively reviewed. Volume segmentation of the cine images to compare the airway volume change over time (mean volume, standard deviation, normalized range, and coefficient of variance) was performed for the capped and uncapped tubes in both the nasopharynx and hypopharynx (Signed Rank Test). Graphical representation of the airway volume over time demonstrates a qualitative increased fluctuation in patients with the tracheotomy tube capped as compared to uncapped in both the nasopharyngeal and hypopharyngeal regions of interest. In the nasopharynx, the mean airway volume (capped 2.72 mL, uncapped 2.09 mL, p = 0.0313), the airway volume standard deviation (capped 0.42 mL, uncapped 0.20 mL, p = 0.0156), and the airway volume range (capped 2.10 mL, uncapped 1.09 mL, p = 0.0156) were significantly larger in the capped group of patients. In the hypopharynx, the airway volume standard deviation (capped 1.54 mL, uncapped 0.67 mL, p = 0.0156), and the airway volume range (capped 6.44 mL, uncapped 2.93 mL, p = 0.0156) were significantly larger in the capped tubes. The coefficient of variance (capped 0.37, uncapped 0.26, p = 0.0469) and the normalized range (capped 1.52, uncapped 1.09, p = 0.0313) were significantly larger in the capped tubes. There is a statistically significant change in airway dynamics in children with tracheotomy tubes when breathing via the airway as compared to breathing via the tracheotomy tube

Histomorphology of the corneal epithelium of anastrozole treated rabbits

International Nuclear Information System (INIS)

Khalil, A.; Qamar, K.; Butt, S.A.

2013-01-01

Objective: To evaluate the effects of prolonged use of anastrozole as an endocrine treatment of breast cancer on the corneal epithelium in an animal model. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College, Rawalpindi in collaboration with National Institute of Health, Islamabad, six months from Jun 2012 to Nov 2012. Material and Methods: Twenty adult female NewZealand white rabbits were taken. Ten rabbits were placed in control group taking normal diet and 10 were given anastrozole orally in the normal dose of 1 mg/day (0.02 mg/kg/day). After the completion of the study, corneas were removed and grossly examined. The specimen were fixed and slides prepared for histomorphological examination. The epithelium in each slide was examined for any deposits, edema or increase in stratification and the height of the epithelium was measured for each eye. The results were compared between the groups for statistical significance. Results: The epithelium had normal shape with no areas of any deposits, edema or ulceration. The mean epithelial height in the control group was 21.25 +- 4.29 mu m and 21.00 +- 4.28 mu m in the right corneas and left corneas, respectively. The mean epithelial height taken from the experimental group was 20.50 +- 4.97 mu m and 21.00 +- 4.28 mu m in right sided and left sided corneas, respectively. The p value was calculated to be 0.722 and 1.00 for the right and left corneas, respectively and no statistical significance was found in between the two groups. Conclusion: Long term administration of anastrozole has no effect on the histological morphology of the corneal epithelium. (author)

Optical coherence tomography of the newborn airway.

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Ridgway, James M; Su, Jianping; Wright, Ryan; Guo, Shuguang; Kim, David C; Barretto, Roberto; Ahuja, Gurpreet; Sepehr, Ali; Perez, Jorge; Sills, Jack H; Chen, Zhongping; Wong, Brian J F

2008-05-01

Acquired subglottic stenosis in a newborn is often associated with prolonged endotracheal intubation. This condition is generally diagnosed during operative endoscopy after airway injury has occurred. Unfortunately, endoscopy is unable to characterize the submucosal changes observed in such airway injuries. Other modalities, such as magnetic resonance imaging, computed tomography, and ultrasound, do not possess the necessary level of resolution to differentiate scar, neocartilage, and edema. Optical coherence tomography (OCT) is an imaging modality that produces high-resolution, cross-sectional images of living tissue (8 to 20 microm). We examined the ability of this noninvasive technique to characterize the newborn airway in a prospective clinical trial. Twelve newborn patients who required ventilatory support underwent OCT airway imaging. Comparative analysis of intubated and non-intubated states was performed. Imaging of the supraglottis, glottis, subglottis, and trachea was performed in 12 patients, revealing unique tissue characteristics as related to turbidity, signal backscattering, and architecture. Multiple structures were identified, including the vocal folds, cricoid cartilage, tracheal rings, ducts, glands, and vessels. Optical coherence tomography clearly identifies in vivo tissue layers and regional architecture while offering detailed information concerning tissue microstructures. The diagnostic potential of this technology makes OCT a promising modality in the study and surveillance of the neonatal airway.

Cyclosporine a inhibits apoptosis of rat gingival epithelium.

Science.gov (United States)

Ma, Su; Liu, Peihong; Li, Yanwu; Hou, Lin; Chen, Li; Qin, Chunlin

2014-08-01

The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia. Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats. CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.

Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

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Marco Schlepütz

Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

Paediatric airway management: basic aspects

DEFF Research Database (Denmark)

Holm-Knudsen, R J; Rasmussen, L S

2009-01-01

Paediatric airway management is a great challenge, especially for anaesthesiologists working in departments with a low number of paediatric surgical procedures. The paediatric airway is substantially different from the adult airway and obstruction leads to rapid desaturation in infants and small...... children. This paper aims at providing the non-paediatric anaesthesiologist with a set of safe and simple principles for basic paediatric airway management. In contrast to adults, most children with difficult airways are recognised before induction of anaesthesia but problems may arise in all children...

Exposure to ozone modulates human airway protease/antiprotease balance contributing to increased influenza A infection.

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Matthew J Kesic

Full Text Available Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs human airway trypsin-like protease (HAT and transmembrane protease, serine 2 (TMPRSS2, whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI. Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility.

COMPARISON OF AIRWAY RESPONSES, HAEMODYNAMICS AND RECOVERY USING SEVOFLURANE AND DESFLURANE VIA LARYNGEAL MASK AIRWAY IN DAY CARE PAEDIATRIC SURGERIES

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A. Satyanarayana

2017-11-01

Full Text Available BACKGROUND The general observation that children achieve better convalescence in the home environment supports the need for adoption of day care surgeries in them. Advantages of paediatric outpatient anaesthesia include- minimises parental separation, uninterrupted feeding schedule/sleeping patterns, less risk of nosocomial infections, reduced cost of hospitalisation, convenience and improved patient satisfaction. The aim of the study is to compare the airway responses, haemodynamic parameters and recovery using sevoflurane and desflurane via laryngeal mask airway in day care paediatric surgeries. MATERIALS AND METHODS 60 paediatric patients of both gender between the age group of 6 and 14 years with ASA grade 1 and 2 undergoing elective day care surgeries under general anaesthesia with LMA are divided into two groups. (Group S sevoflurane group received sevoflurane 2% to 3% and (group D desflurane group received desflurane 6% to 8% for maintenance of anaesthesia after induction with IV propofol 2 mg/kg. Airway responses, haemodynamics and recovery parameters are recorded. RESULTS Recovery parameters spontaneous eye opening, response to verbal commands, Aldrete score at 5 and 10 mins. showed statistically significant difference between two groups. Recovery is faster in desflurane group compared to sevoflurane group. The airway responses and adverse events were found to be more in desflurane group, but statistically not significant. CONCLUSION Recovery from anaesthesia was faster in patients maintained with desflurane (6% to 8% compared with sevoflurane (2% to 3%.

DIFFERENTIAL HISTOMORPHOMETRIC CHANGES IN NORMAL AND INFLAMED GINGIVAL EPITHELIUM

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Tanaskovic Stankovic Sanja

2016-12-01

Full Text Available Introduction and aim: In recent decades, many factors such as smoking, unhealthy diet as well as high alcohol intake were marked as risk factors that can lead to increased incidence of malignant alterations, gingivitis, periodontal disease and other oral epithelium pathological changes. Having in mind that in the group of non-malignant and non-dental oral pathology gingivitis and periodontal disease are the most common oral mucosa alterations aim of our research was to investigate histomorphometric characteristics of healthy and altered oral and gingival epithelium. Material and methods: Tissue samples of 24 oral and gingival mucosa specimens were collected. Samples were fixed in 10% buffered paraformaldehyde, routinely processed and embedded in paraffin blocks. From each block sections 5 micrometer thin were made and standard H/E staining as well as immunocytochemical detection of Ki-67 proliferation marker and CD79a lymphocyte marker were performed. Measurements and image analysis was performed with Image Pro Plus software (Media Cybernetics, USA and Axiovision (Ziess, USA. Results: We showed that inflamed gingival epithelium is increasing its thickness in proportion to the severity of adjacent inflammation. Furthermore, mitotic index is rising (up to 132% in the same manner as well as basal lamina length (up to 70% when normal and inflamed gingiva is compared. Architecture of epithelial ridges is changed from straightforward to mesh-like. Conclusion: Assessment of the free gingival epithelium thickness is directly related to the severity of the inflammation process i

TR146 cells grown on filters as a model of human buccal epithelium

DEFF Research Database (Denmark)

Mørck Nielsen, H; Rømer Rassing, M; Nielsen, Hanne Mørck

2000-01-01

cell culture model, and human and porcine buccal epithelium were compared. The esterase activity in the intact cell culture model and in the porcine buccal mucosa was compared. Further, the TR146 cell culture model was used to study the permeability rate and metabolism of leu-enkephalin. The activity...... of the three enzymes in the TR146 homogenate supernatants was in the same range as the activity in homogenate supernatants of human buccal epithelium. In the TR146 cell culture model, the activity of aminopeptidase (13.70+/-2.10 nmol/min per mg protein) was approx. four times the activity of carboxypeptidase...

Effect of Class III bone anchor treatment on airway.

Science.gov (United States)

Nguyen, Tung; De Clerck, Hugo; Wilson, Michael; Golden, Brent

2015-07-01

To compare airway volumes and minimum cross-section area changes of Class III patients treated with bone-anchored maxillary protraction (BAMP) versus untreated Class III controls. Twenty-eight consecutive skeletal Class III patients between the ages of 10 and 14 years (mean age, 11.9 years) were treated using Class III intermaxillary elastics and bilateral miniplates (two in the infra-zygomatic crests of the maxilla and two in the anterior mandible). The subjects had cone beam computed tomographs (CBCTs) taken before initial loading (T1) and 1 year out (T2). Twenty-eight untreated Class III patients (mean age, 12.4 years) had CBCTs taken and cephalograms generated. The airway volumes and minimum cross-sectional area measurements were performed using Dolphin Imaging 11.7 3D software. The superior border of the airway was defined by a plane that passes through the posterior nasal spine and basion, while the inferior border included the base of the epiglottis to the lower border of C3. From T1 to T2, airway volume from BAMP-treated subjects showed a statistically significant increase (1499.64 mm(3)). The area in the most constricted section of the airway (choke point) increased slightly (15.44 mm(2)). The airway volume of BAMP patients at T2 was 14136.61 mm(3), compared with 14432.98 mm(3) in untreated Class III subjects. Intraexaminer correlation coefficients values and 95% confidence interval values were all greater than .90, showing a high degree of reliability of the measurements. BAMP treatment did not hinder the development of the oropharynx.

Epithelial expression of TLR4 is modulated in COPD and by steroids, salmeterol and cigarette smoke

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Dorscheid Delbert R

2007-11-01

Full Text Available Abstract The toll-like receptors (TLRs are a key component of host defense in the respiratory epithelium. Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations. We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged. Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression. We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease. Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts. Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein. The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS. Stimulation with salmeterol (10-6 M caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect. The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression. Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens.

Targeting Phosphoinositide 3-Kinase γ in Airway Smooth Muscle Cells to Suppress Interleukin-13-Induced Mouse Airway Hyperresponsiveness

Science.gov (United States)

Jiang, Haihong; Xie, Yan; Abel, Peter W.; Toews, Myron L.; Townley, Robert G.; Casale, Thomas B.

2012-01-01

We recently reported that phosphoinositide 3-kinase γ (PI3Kγ) directly regulates airway smooth muscle (ASM) contraction by modulating Ca2+ oscillations. Because ASM contraction plays a critical role in airway hyperresponsiveness (AHR) of asthma, the aim of the present study was to determine whether targeting PI3Kγ in ASM cells could suppress AHR in vitro and in vivo. Intranasal administration into mice of interleukin-13 (IL-13; 10 μg per mouse), a key pathophysiologic cytokine in asthma, induced AHR after 48 h, as assessed by invasive tracheostomy. Intranasal administration of a broad-spectrum PI3K inhibitor or a PI3Kγ-specific inhibitor 1 h before AHR assessment attenuated IL-13 effects. Airway responsiveness to bronchoconstrictor agonists was also examined in precision-cut mouse lung slices pretreated without or with IL-13 for 24 h. Acetylcholine and serotonin dose-response curves indicated that IL-13-treated lung slices had a 40 to 50% larger maximal airway constriction compared with controls. Furthermore, acetylcholine induced a larger initial Ca2+ transient and increased Ca2+ oscillations in IL-13-treated primary mouse ASM cells compared with control cells, correlating with increased cell contraction. As expected, PI3Kγ inhibitor treatment attenuated IL-13-augmented airway contractility of lung slices and ASM cell contraction. In both control and IL-13-treated ASM cells, small interfering RNA-mediated knockdown of PI3Kγ by 70% only reduced the initial Ca2+ transient by 20 to 30% but markedly attenuated Ca2+ oscillations and contractility of ASM cells by 50 to 60%. This report is the first to demonstrate that PI3Kγ in ASM cells is important for IL-13-induced AHR and that acute treatment with a PI3Kγ inhibitor can ameliorate AHR in a murine model of asthma. PMID:22543031

Airway management in trauma.

Science.gov (United States)

Langeron, O; Birenbaum, A; Amour, J

2009-05-01

Maintenance of a patent and prevention of aspiration are essential for the management of the trauma patient, that requires experienced physicians in airway control techniques. Difficulties of the airway control in the trauma setting are increased by the vital failures, the risk of aspiration, the potential cervical spine injury, the combative patient, and the obvious risk of difficult tracheal intubation related to specific injury related to the trauma. Endotracheal intubation remains the gold standard in trauma patient airway management and should be performed via the oral route with a rapid sequence induction and a manual in-line stabilization maneuver, to decrease the risks previously mentioned. Different techniques to control the airway in trauma patients are presented: improvement of the laryngoscopic vision, lighted stylet tracheal intubation, retrograde technique for orotracheal intubation, the laryngeal mask and the intubating laryngeal mask airways, the combitube and cricothyroidotomy. Management of the airway in trauma patients requires regular training in these techniques and the knowledge of complementary techniques allowing tracheal intubation or oxygenation to overcome difficult intubation and to prevent major complications as hypoxemia and aspiration.

Comparison of transepithelial corneal crosslinking with epithelium-off crosslinking (epithelium-off CXL in adult Pakistani population with progressive keratoconus

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Bushra Akbar

2017-01-01

CONCLUSION: Transepithelial CXL is not recommended to be replaced completely by standard epithelium-off CXL due to continued ectatic progression in 25% of cases. However, thin corneas, unfit for standard epithelium-off CXL, can benefit from transepithelial CXL.

[Alterations in the metabolism of cornmeal epithelium during medium-term storage (author's transl)].

Science.gov (United States)

Schmidt-Martens, F W; Hennighausen, U; Wirz, K; Teping, C

1977-08-08

Freshly prepared bovine corneas were stored in medium TC 199 with penicillin and fetal calf serum at +4 degrees C over a storage period of 168h. Every 24h, the levels of glucose, lactate, and pyruvate in the corneal epithelium were estimated. Also the glucose levels in the corneal epithelium and stroma were compared at the same time intervals. Furthermore, alterations in the enzyme pattern of the epithelial cells during storage were observed.

Secreted osteopontin is highly polymerized in human airways and fragmented in asthmatic airway secretions.

Directory of Open Access Journals (Sweden)

Mehrdad Arjomandi

Full Text Available Osteopontin (OPN is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma.To determine whether secreted OPN (sOPN is polymerized in human airways and whether it is qualitatively different in asthma, we used immunoblotting to examine sOPN in bronchoalveolar lavage (BAL fluid samples from 12 healthy and 21 asthmatic subjects (and in sputum samples from 27 healthy and 21 asthmatic subjects. All asthmatic subjects had mild to moderate asthma and abstained from corticosteroids during the study. Furthermore, we examined the relationship between airway sOPN and cellular inflammation.We found that sOPN in BAL fluid and sputum exists in polymeric, monomeric, and cleaved forms, with most of it in polymeric form. Compared to healthy subjects, asthmatic subjects had proportionately less polymeric sOPN and more monomeric and cleaved sOPN. Polymeric sOPN in BAL fluid was associated with increased alveolar macrophage counts in airways in all subjects.These results suggest that sOPN in human airways (1 undergoes extensive post-translational modification by polymerization and proteolytic fragmentation, (2 is more fragmented and less polymerized in subjects with mild to moderate asthma, and (3 may contribute to recruitment or survival of alveolar macrophages.

The Laryngeal Mask Airway (LMA) as an alternative to airway ...

African Journals Online (AJOL)

Background: To evaluate the possibility of airway management using a laryngeal mask airway (LMA) during dental procedures on mentally retarded (MR) patients and patients with genetic diseases. Design: A prospective pilot study. Setting: University Hospital. Methods: A pilot study was designed to induce general ...

Genotoxic differences by sex in nasal epithelium and blood leukocytes in subjects residing in a highly polluted area

International Nuclear Information System (INIS)

Fortoul, T.I.; Valverde, M.; Lopez, M.C.; Avila-Costa, M.R.; Avila-Casado, M.C.; Mussali-Galante, P.; Gonzalez-Villalva, A.; Rojas, E.; Ostrosky-Shejet, P.

2004-01-01

We describe differences by sex in genotoxic damage found in a population of medical students exposed to a highly oxidative atmosphere, compared with a control group, measured by the single-cell gel electrophoresis assay and histological changes in nasal epithelium smears. Cells were obtained from the nasal epithelium and blood leukocytes. Higher DNA damage in nasal cells and leukocytes was found in males compared to females and control subjects. The percentage of squamous metaplastic changes in the nasal epithelium was also higher in males compared with females and controls. The commutation of normal nasal epithelium by squamous cells might modify its protective function in the nose, increasing the risk of damage to the lower respiratory tract. Although, as medical students, males and females were exposed to the same environment and activity patterns, male genotoxicity damage was higher in control and exposed subjects. More research should be done in order to identify direct or indirect sexual hormone intervention

Comparative study of patients suffering sore throat after general anesthesia using laryngeal mask airway and cuffed pharyngeal tube in adults

Directory of Open Access Journals (Sweden)

Hassani V

2001-09-01

Full Text Available Post-operative sore throat is one of the most common complications and complaints of patients after general anesthesia especially in operations that need endotracheal intubations. Its causes are: size of endotracheal tube and type of its cuff, inadequate airway humidification, trauma during intubation and suctioning, high flow of inspiratory gases, surgical manipulation of airway and adjacent organs, ect. Use of instruments with less invasion to upper respiratory tract, for example, face mask and airway, LMA or CPT are methods, used for decreasing the rate of post-operative sore throat. This study was performed to compare the rate of sore throat after general anesthesia between Laryngeal Mask Airway (LMA and Cuffed Pharyngeal Tube (CPT. From the patients, 120 ASA: PS-I cases, were selected, who were candidates for elective surgery of Orthopedics, Urology, General surgery and Gynecology in Hazrat Rasool-Akram Hospital Complex in the year 2000. Their operation were performed in supine position and did not need muscle relaxation and the patients had spontaneous breathing. Duration of surgery was less than 2 hours. The patients were randomly allocated into two groups: LMA was used for one group and CPT for others. Immediately after operation, in the recovery room and at 6, 12, 18 and 24 hours after removing the tube, the patients were asked about sore throat and the results were recorded in the related sheets. The results was 31.7 percent of patients in group LMA and 0 percent of patients in group CPT, had sore throat. There were significant difference between groups (LMA and CPT in presentation of sore throat (P<0.001.

Mucociliary clearance, airway inflammation and nasal symptoms in urban motorcyclists

Directory of Open Access Journals (Sweden)

Tereza C.S. Brant

2014-01-01

Full Text Available OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS: In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO2 concentration-monitoring system during the 14 days before each assessment. The associations between NO2 and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: NCT01976039. RESULTS: Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO2 exposure level was 75 mg/m3 for these subjects and a significant association was observed between NO2 and impaired mucociliary clearance (p = 0.036. CONCLUSION: Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.

Gefitinib, an EGFR Tyrosine Kinase inhibitor, Prevents Smoke-Mediated Ciliated Airway Epithelial Cell Loss and Promotes Their Recovery.

Directory of Open Access Journals (Sweden)

Monica Valencia-Gattas

Full Text Available Cigarette smoke exposure is a major health hazard. Ciliated cells in the epithelium of the airway play a critical role in protection against the noxious effects of inhaled cigarette smoke. Ciliated cell numbers are reduced in smokers which weakens host defense and leads to disease. The mechanisms for the loss of ciliated cells are not well understood. The effects of whole cigarette smoke exposure on human airway ciliated ciliated cells were examined using in vitro cultures of normal human bronchial epithelial cells and a Vitrocell® VC 10® Smoking Robot. These experiments showed that whole cigarette smoke causes the loss of differentiated ciliated cells and inhibits differentiation of ciliated cells from undifferentiated basal cells. Furthermore, treatment with the epidermal growth factor receptor (EGFR tyrosine kinase inhibitor, Gefitinib, during smoke exposure prevents ciliated cell loss and promotes ciliated cell differentiation from basal cells. Finally, restoration of ciliated cells was inhibited after smoke exposure was ceased but was enhanced by Gefitinib treatment. These data suggest that inhibition of EGFR activity may provide therapeutic benefit for treating smoke related diseases.

Proportional positive airway pressure: a new concept to treat obstructive sleep apnoea.

Science.gov (United States)

Juhász, J; Becker, H; Cassel, W; Rostig, S; Peter, J H

2001-03-01

Proportional positive airway pressure (PPAP) was designed to optimize airway pressure for the therapy of obstructive sleep apnoea (OSA). In a randomized crossover prospective study, the clinical feasibility of PPAP and its immediate effects on the breathing disorder and sleep in comparison with continuous positive airway pressure (CPAP) was evaluated. Twelve patients requiring CPAP therapy underwent CPAP and PPAP titration in a random order. Obstructive and mixed respiratory events could be completely abolished with both forms of treatment. This efficacy could be achieved at a significantly lower mean mask pressure during PPAP titration (8.45+/-2.42 cmH2O) compared to CPAP (9.96+/-2.7 cmH2O) (p=0.002). The mean minimal arterial oxygen saturation (Sa,O2) (82.8+/-6.5%) on the diagnostic night increased significantly (pPPAP titration. Total sleep time, slow wave sleep and rapid eye movement (REM) sleep increased significantly by the same amount during both CPAP and PPAP titration (pPPAP titration night, four patients did not have a preference, and two patients preferred CPAP. The present data show that proportional positive airway pressure is as effective as continuous positive airway pressure in eliminating obstructive events and has the same immediate effect on sleep. The lower average mask pressure during proportional positive airway pressure implies potential advantages compared to continuous positive airway pressure. Proportional positive airway pressure presents a new effective therapeutic approach to obstructive sleep apnoea.

Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles

International Nuclear Information System (INIS)

Tal, Tamara L.; Simmons, Steven O.; Silbajoris, Robert; Dailey, Lisa; Cho, Seung-Hyun; Ramabhadran, Ram; Linak, William; Reed, William; Bromberg, Philip A.; Samet, James M.

2010-01-01

Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in airway epithelial cells, a principal target of inhaled DEP. IL-8 is a proinflammatory chemokine expressed by the airway epithelium in response to environmental pollutants. The mechanism by which DEP exposure induces IL-8 expression is not well understood. In the current study, we sought to determine whether DEP with varying organic content induces IL-8 expression in lung epithelial cells, as well as, to develop a method to rapidly evaluate the upstream mechanism(s) by which DEP induces IL-8 expression. Exposure to DEP with varying organic content differentially induced IL-8 expression and IL-8 promoter activity human airway epithelial cells. Mutational analysis of the IL-8 promoter was also performed using recombinant human cell lines expressing reporters linked to the mutated promoters. Treatment with a low organic-containing DEP stimulated IL-8 expression by a mechanism that is predominantly NFkB-dependent. In contrast, exposure to high organic-containing DEP induced IL-8 expression independently of NFkB through a mechanism that requires AP-1 activity. Our study reveals that exposure to DEP of varying organic content induces proinflammatory gene expression through multiple specific mechanisms in human airway epithelial cells. The approaches used in the present study demonstrate the utility of a promoter-reporter assay ensemble for identifying transcriptional pathways activated by pollutant exposure.

Neoplasia versus hyperplasia of the retinal pigment epithelium

DEFF Research Database (Denmark)

Heegaard, Steffen; Larsen, J.N.B.; Fledelius, Hans C.

2001-01-01

ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography......ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography...

Relapsing polychondritis and airway involvement.

Science.gov (United States)

Ernst, Armin; Rafeq, Samaan; Boiselle, Phillip; Sung, Arthur; Reddy, Chakravarthy; Michaud, Gaetane; Majid, Adnan; Herth, Felix J F; Trentham, David

2009-04-01

To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP). Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008. RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention. In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.

Assessment of airway compression on chest radiographs in children with pulmonary tuberculosis

International Nuclear Information System (INIS)

Richter-Joubert, Lisel; Andronikou, Savvas; Workman, Lesley; Zar, Heather J.

2017-01-01

Because small, pliable paediatric airways are easily compressed by enlarged lymph nodes, detection of radiographic airway compression might be an objective criterion for diagnosing pulmonary tuberculosis. To investigate the frequency and inter-observer agreement of airway compression on chest radiographs in children with pulmonary tuberculosis compared to those with a different lower respiratory tract infection. Chest radiographs of children with suspected pulmonary tuberculosis were read by two readers according to a standardised format and a third reader when there was disagreement. Radiographs of children with proven pulmonary tuberculosis were compared to those with a different lower respiratory tract infection. We evaluated frequency and location of radiographic airway compression. Findings were correlated with human immunodeficiency virus (HIV) status and age. We assessed inter-observer agreement using kappa statistics. We reviewed radiographs of 505 children (median age 25.9 months, interquartile range [IQR] 14.3-62.2). Radiographic airway compression occurred in 54/188 (28.7%) children with proven pulmonary tuberculosis and in 24/317 (7.6%) children with other types of lower respiratory tract infection (odds ratio [OR] 4.9; 95% confidence interval [CI] 2.9-8.3). A higher frequency of radiographic airway compression occurred in infants (22/101, or 21.8%) compared to older children (56/404, or 13.9%; OR 1.7; 95% CI 1.0-3.0). We found no association between airway compression and HIV infection. Inter-observer agreement ranged from none to fair (kappa of 0.0-0.4). There is a strong association between airway compression on chest radiographs and confirmed pulmonary tuberculosis. However this finding's clinical use as an objective criterion for diagnosis of pulmonary tuberculosis in children is limited by poor inter-observer agreement. (orig.)

Assessment of airway compression on chest radiographs in children with pulmonary tuberculosis

Energy Technology Data Exchange (ETDEWEB)

Richter-Joubert, Lisel [Groote Schuur Hospital and University of Cape Town, Department of Radiology, Cape Town (South Africa); Andronikou, Savvas [Groote Schuur Hospital and University of Cape Town, Department of Radiology, Cape Town (South Africa); Bristol Royal Hospital for Children and the University of Bristol, Department of Paediatric Radiology, Bristol (United Kingdom); Workman, Lesley; Zar, Heather J. [University of Cape Town, Department of Paediatrics and Child Health and MRC Unit on Child and Adolescent Health, Red Cross War Memorial Children' s Hospital, Cape Town (South Africa)

2017-09-15

Because small, pliable paediatric airways are easily compressed by enlarged lymph nodes, detection of radiographic airway compression might be an objective criterion for diagnosing pulmonary tuberculosis. To investigate the frequency and inter-observer agreement of airway compression on chest radiographs in children with pulmonary tuberculosis compared to those with a different lower respiratory tract infection. Chest radiographs of children with suspected pulmonary tuberculosis were read by two readers according to a standardised format and a third reader when there was disagreement. Radiographs of children with proven pulmonary tuberculosis were compared to those with a different lower respiratory tract infection. We evaluated frequency and location of radiographic airway compression. Findings were correlated with human immunodeficiency virus (HIV) status and age. We assessed inter-observer agreement using kappa statistics. We reviewed radiographs of 505 children (median age 25.9 months, interquartile range [IQR] 14.3-62.2). Radiographic airway compression occurred in 54/188 (28.7%) children with proven pulmonary tuberculosis and in 24/317 (7.6%) children with other types of lower respiratory tract infection (odds ratio [OR] 4.9; 95% confidence interval [CI] 2.9-8.3). A higher frequency of radiographic airway compression occurred in infants (22/101, or 21.8%) compared to older children (56/404, or 13.9%; OR 1.7; 95% CI 1.0-3.0). We found no association between airway compression and HIV infection. Inter-observer agreement ranged from none to fair (kappa of 0.0-0.4). There is a strong association between airway compression on chest radiographs and confirmed pulmonary tuberculosis. However this finding's clinical use as an objective criterion for diagnosis of pulmonary tuberculosis in children is limited by poor inter-observer agreement. (orig.)

Specific airway resistance in healthy young Vietnamese and Caucasian adults.

Science.gov (United States)

Le Tuan, Thanh; Nguyen, Ngoc Minh; Demoulin, Bruno; Bonabel, Claude; Nguyen-Thi, Phi Linh; Ioan, Iulia; Schweitzer, Cyril; Nguyen, H T T; Varechova, Silvia; Marchal, Francois

2015-06-01

In healthy Vietnamese children the respiratory resistance has been suggested to be similar at 110 cm height but larger at 130 cm when compared with data in Caucasians from the literature, suggesting smaller airways in older Vietnamese children (Vu et al., 2008). The hypothesis tested here is whether the difference in airway resistance remains consistent throughout growth, and if it is larger in adult Vietnamese than in Caucasians. Airway resistance and Functional Residual Capacity were measured in healthy young Caucasian and Vietnamese adults in their respective native country using identical equipment and protocols. Ninety five subjects in Vietnam (60 males) and 101 in France (41 males) were recruited. Airway resistance was significantly larger in Vietnamese than in Caucasians and in females than in males, consistent with difference in body dimensions. Specific airway resistance however was not different by ethnicity or gender. The findings do not support the hypothesis that airway size at adult age - once normalized for lung volume - differs between Vietnamese and Caucasians. Copyright © 2015 Elsevier B.V. All rights reserved.

Detailed statistical analysis plan for the difficult airway management (DIFFICAIR) trial

DEFF Research Database (Denmark)

Nørskov, Anders Kehlet; Lundstrøm, Lars Hyldborg; Rosenstock, Charlotte Vallentin

2014-01-01

BACKGROUND: Preoperative airway assessment in Denmark is based on a non-specific clinical assessment left to the discretion of the responsible anesthesiologist. The DIFFICAIR trial compares the effect of using a systematic and consistent airway assessment versus a non-specific clinical assessment...

Oestrus synchronization treatment induces histomorphological changes on the uterine tube epithelium of the gilt.

Science.gov (United States)

Juárez-Mosqueda, M L; Anzaldúa Arce, S R; Palma Lara, I; García Dalmán, C; Cornejo Cortés, M A; Córdova Izquierdo, A; Villaseñor Gaona, H; Trujillo Ortega, M E

2015-12-01

The aim of this study was to determine the histomorphological changes that occurred in response to two treatments for oestrus synchronization in three different regions of the gilt's uterine tubes epithelium: the ampulla (AMP), ampulla-isthmic junction (AIJ) and isthmus (IST). Nine prepuberal gilts were divided into three groups (n = 3): (1) eCG 400 IU and hCG 200 IU (eCG/hCG), (2) progesterone agonist (P4) and (3) control group. The number of secretory cells (stained with periodic acid-Schiff reaction or PAS-positive cells) decreased in the AMP in the P4 treated group when compared to the control group, whereas, no difference was observed in the number of PAS-negative cells in the AMP of the three groups. A significant decrease in the number of PAS-positive cells was observed in the AIJ and IST of the P4 treated group when compared to the eCG/hCG and control groups. An increase in the number of PAS-negative cells was observed in the AIJ and IST in the P4 treated group. The epithelium height in the AMP and AIJ was increased in the eCG/hCG group when compared to the control and P4 groups. In this last group, we observed a reduced height compared with the other two groups for the AIJ. In the IST, there were no significant changes in the epithelium height of the control or the other two groups (eCG/hCG and P4). The epithelial cells of the P4 treated group had the least amount of cytoplasmic granules and the lowest intensity of PAS staining in the AMP, AIJ and IST. Animals treated with eCG/hCG showed an intermediate number of cytoplasmic granules and intensity in all regions evaluated. These data show that P4 treatment for synchronization induces a significant (P epithelium. Moreover, eCG/hCG treatment increased the height of the epithelium in the AMP and AIJ, while in this last region, the P4 treatment decreased the epithelium height. These results show that synchronization treatments with P4 and in a smaller proportion with eCG/hCG can modify the amount of PAS

Barrier properties of cultured retinal pigment epithelium.

Science.gov (United States)

Rizzolo, Lawrence J

2014-09-01

The principal function of an epithelium is to form a dynamic barrier that regulates movement between body compartments. Each epithelium is specialized with barrier functions that are specific for the tissues it serves. The apical surface commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a thin (subretinal) space that can become fluid filled during pathology. RPE separates the subretinal space from the blood supply of the outer retina, thereby forming the outer blood-retinal barrier. The intricate interaction between the RPE and sensory retina presents challenges for learning how accurately culture models reflect native behavior. The challenge is heightened by findings that detail the variation of RPE barrier proteins both among species and at different stages of the life cycle. Among the striking differences is the expression of claudin family members. Claudins are the tight junction proteins that regulate ion diffusion across the spaces that lie between the cells of a monolayer. Claudin expression by RPE varies with species and life-stage, which implies functional differences among commonly used animal models. Investigators have turned to transcriptomics to supplement functional studies when comparing native and cultured tissue. The most detailed studies of the outer blood-retinal barrier have focused on human RPE with transcriptome and functional studies reported for human fetal, adult, and stem-cell derived RPE. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of different toxicity assays applied to proliferating cells and to stratified epithelium in relation to permeability enhancement with glycocholate

DEFF Research Database (Denmark)

Eirheim, Heidi Ugelstad; Bundgaard, Christoffer; Nielsen, Hanne Mørck

2004-01-01

The purpose of the present study was to evaluate different toxicity assays for use on proliferating buccal TR146 cells and on stratified TR146 epithelium and to compare these results to the permeability enhancing effect of glycocholate (GC). Both the proliferating cells and the epithelium were...... across the epithelium concurrent with a decrease in the transepithelial electrical resistance (TEER) was also determined. The robustness of the epithelium was significantly higher than that of the proliferating cells (P...

Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum

International Nuclear Information System (INIS)

Lepor, H.; Rigaud, G.; Shapiro, E.; Baumann, M.; Kodner, I.J.; Fleshman, J.W.

1990-01-01

The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments

Prevalence of ciliated epithelium in apical periodontitis lesions.

Science.gov (United States)

Ricucci, Domenico; Loghin, Simona; Siqueira, José F; Abdelsayed, Rafik A

2014-04-01

This article reports on the morphologic features and the frequency of ciliated epithelium in apical cysts and discusses its origin. The study material consisted of 167 human apical periodontitis lesions obtained consecutively from patients presenting for treatment during a period of 12 years in a dental practice operated by one of the authors. All of the lesions were obtained still attached to the root apices of teeth with untreated (93 lesions) or treated canals (74 lesions). The former were obtained by extraction and the latter by extraction or apical surgery. Specimens were processed for histopathologic and histobacteriologic analyses. Lesions were classified, and the type of epithelium, if present, was recorded. Of the lesions analyzed, 49 (29%) were diagnosed as cysts. Of these, 26 (53%) were found in untreated teeth, and 23 (47%) related to root canal-treated teeth. Ciliated columnar epithelium was observed partially or completely lining the cyst wall in 4 cysts, and all of them occurred in untreated maxillary molars. Three of these lesions were categorized as pocket cysts, and the other was a true cyst. Ciliated columnar epithelium-lined cysts corresponded to approximately 2% of the apical periodontitis lesions and 8% of the cysts of endodontic origin in the population studied. This epithelium is highly likely to have a sinus origin in the majority of cases. However, the possibility of prosoplasia or upgraded differentiation into ciliated epithelium from the typical cystic lining squamous epithelium may also be considered. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Cellular morphometry and cycling cell populations of human and dog bronchi. Final report, April 1, 1988 - December 31, 1996

International Nuclear Information System (INIS)

Robbins, E.S.

1996-12-01

Quantitative data of the human bronchial epithelial cells at possible risk for malignant transformation in lung cancer is crucial for accurate radon dosimetry and risk analysis. The locations and other parameters of the nuclei which may be damaged by α particles and develop into cancers have been determined and compared in different airway generations, among smokers, non-smokers and ex-smokers, between men and women and in people of different ages. This research included extended morphometric studies on electron micrographs of human epithelium of defined airway generations. Since cycling cells can be more sensitive to damage from carcinogens and radioactivity, a second major part of this research consisted of studies to quantitate the cycling tracheobronchial epithelial population(s) using immunocytochemistry and the proliferation marker PCNA on paraffin sections. The basal and suprabasal cycling cell populations of the bronchi of smokers, non-smokers, and ex-smokers, men and women were compared. Normal human airway linings were also compared with normal adult dog trachea and bronchi as well as metaplastic and repairing human airways. The quantitative data from this project resulted in several publications on the cycling and putative stem cells of the tracheobronchial epithelium and more accurate radon dosimetry and risk analyses

Protection of the Peyer's patch-associated crypt and villus epithelium against methotrexate-induced damage is based on its distinct regulation of proliferation

NARCIS (Netherlands)

Renes, Ingrid B.; Verburg, Melissa; Bulsing, Nathalie P.; Ferdinandusse, Sacha; Büller, Hans A.; Dekker, Jan; Einerhand, Alexandra W. C.

2002-01-01

The crypt and villus epithelium associated with Peyer's patches (PPs) is largely spared from methotrexate (MTX)-induced damage, compared with the non-patch (NP) epithelium. To assess the mechanism(s) preventing damage to the PP epithelium after MTX treatment, epithelial proliferation, apoptosis, and

Relationship between airway pathophysiology and airway inflammation in older asthmatics

DEFF Research Database (Denmark)

Porsbjerg, Celeste M; Gibson, Peter G; Pretto, Jeffrey J

2013-01-01

-dose ratio (%fall in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO). RESULTS...

Elevation of susceptibility to ozone-induced acute tracheobronchial injury in transgenic mice deficient in Clara cell secretory protein

International Nuclear Information System (INIS)

Plopper, C.G.; Mango, G.W.; Hatch, G.E.; Wong, V.J.; Toskala, E.; Reynolds, S.D.; Tarkington, B.K.; Stripp, B.R.

2006-01-01

Increases in Clara cell abundance or cellular expression of Clara cell secretory protein (CCSP) may cause increased tolerance of the lung to acute oxidant injury by repeated exposure to ozone (O 3 ). This study defines how disruption of the gene for CCSP synthesis affects the susceptibility of tracheobronchial epithelium to acute oxidant injury. Mice homozygous for a null allele of the CCSP gene (CCSP-/-) and wild type (CCSP+/+) littermates were exposed to ozone (0.2 ppm, 8 h; 1 ppm, 8 h) or filtered air. Injury was evaluated by light and scanning electron microscopy, and the abundance of necrotic, ciliated, and nonciliated cells was estimated by morphometry. Proximal and midlevel intrapulmonary airways and terminal bronchioles were evaluated. There was no difference in airway epithelial composition between CCSP+/+ and CCSP-/- mice exposed to filtered air, and exposure to 0.2 ppm ozone caused little injury to the epithelium of both CCSP+/+ and CCSP-/- mice. After exposure to 1.0 ppm ozone, CCSP-/- mice suffered from a greater degree of epithelial injury throughout the airways compared to CCSP+/+ mice. CCSP-/- mice had both ciliated and nonciliated cell injury. Furthermore, lack of CCSP was associated with a shift in airway injury to include proximal airway generations. Therefore, we conclude that CCSP modulates the susceptibility of the epithelium to oxidant-induced injury. Whether this is due to the presence of CCSP on the acellular lining layer surface and/or its intracellular distribution in the secretory cell population needs to be defined

Automatic 2D segmentation of airways in thorax computed tomography images

International Nuclear Information System (INIS)

Cavalcante, Tarique da Silveira; Cortez, Paulo Cesar; Almeida, Thomaz Maia de; Felix, John Hebert da Silva; Holanda, Marcelo Alcantara

2013-01-01

Introduction: much of the world population is affected by pulmonary diseases, such as the bronchial asthma, bronchitis and bronchiectasis. The bronchial diagnosis is based on the airways state. In this sense, the automatic segmentation of the airways in Computed Tomography (CT) scans is a critical step in the aid to diagnosis of these diseases. Methods: this paper evaluates algorithms for airway automatic segmentation, using Neural Network Multilayer Perceptron (MLP) and Lung Densities Analysis (LDA) for detecting airways, along with Region Growing (RG), Active Contour Method (ACM) Balloon and Topology Adaptive to segment them. Results: we obtained results in three stages: comparative analysis of the detection algorithms MLP and LDA, with a gold standard acquired by three physicians with expertise in CT imaging of the chest; comparative analysis of segmentation algorithms ACM Balloon, ACM Topology Adaptive, MLP and RG; and evaluation of possible combinations between segmentation and detection algorithms, resulting in the complete method for automatic segmentation of the airways in 2D. Conclusion: the low incidence of false negative and the significant reduction of false positive, results in similarity coefficient and sensitivity exceeding 91% and 87% respectively, for a combination of algorithms with satisfactory segmentation quality. (author)

Crisis management during anaesthesia: obstruction of the natural airway.

Science.gov (United States)

Visvanathan, T; Kluger, M T; Webb, R K; Westhorpe, R N

2005-06-01

Obstruction of the natural airway, while usually easily recognised and managed, may present simply as desaturation, have an unexpected cause, be very difficult to manage, and have serious consequences for the patient. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a specific sub-algorithm for obstruction of the natural airway, in the management of acute airway obstruction occurring in association with anaesthesia. The potential performance for this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. There were 62 relevant incidents among the first 4000 reports to the AIMS. It was considered that the correct use of the structured approach would have led to earlier recognition of the problem and/or better management in 11% of cases. Airway management is a fundamental anaesthetic responsibility and skill. Airway obstruction demands a rapid and organised approach to its diagnosis and management and undue delay usually results in desaturation and a potential threat to life. An uncomplicated pre-learned sequence of airway rescue instructions is an essential part of every anaesthetist's clinical practice requirements.

Long-term clearance from small airways in subjects with ciliary dysfunction

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Hjelte Lena

2006-05-01

Full Text Available Abstract The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function. Six young adults with primary ciliary dyskinesia (PCD inhaled 111 Indium labelled Teflon particles of 4.2 μm geometric and 6.2 μm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasions up to 21 days after inhalation. Results were compared with data from ten healthy controls. For additional comparison three of the PCD subjects also inhaled the test particles with normal inhalation flow, 0.5 L/s, providing a more central deposition. The lung retention at 24 h in % of lung deposition (Ret24 was higher (p 24 with slow inhalation flow was 73.9 ± 1.9 % compared to 68.9 ± 7.5 % with normal inhalation flow in the three PCD subjects exposed twice. During day 7–21 the three PCD subjects exposed twice cleared 9 % with normal flow, probably representing predominantly alveolar clearance, compared to 19 % with slow inhalation flow, probably representing mainly small airway clearance. This study shows that despite ciliary dysfunction, clearance continues in the small airways beyond 24 h. There are apparently additional clearance mechanisms present in the small airways.

Cytofluorophotometrical study of the DNA content of the uterine cervical carcinoma and the vaginal epithelium

International Nuclear Information System (INIS)

Tokumoto, Yoshiaki

1987-01-01

The Feulgen DNA content in cells of uterine cervical carcinoma and that of its adjacent vaginal epithelium were measured by microfluorophotometry. The Feulgen DNA content in cells of uterine cervical carcinoma was increased and showed a greater variation of its DNA values compared with diploid cells. The Feulgen DNA content in cells of normal vaginal epithelium adjacent to cervical carcinoma was also increased compared with diploid cells in 6 out of 8 cases. The relativity between the cellular DNA content of cervical carcinoma and that of its adjacent normal vaginal epithelium was found. In 10 out of 14 cases of uterine cervical carcinoma, the mean value of cellular DNA content was increased after by therapuetic irradiation with 10 Gy. Radiation effects on the DNA content of vaginal epithelial cells were similar to those on the DNA content of carcinoma cells. (author)

Acid phosphatase and lipid peroxidation in human cataractous lens epithelium

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Vasavada Abhay

1993-01-01

Full Text Available The anterior lens epithelial cells undergo a variety of degenerative and proliferative changes during cataract formation. Acid phosphatase is primarily responsible for tissue regeneration and tissue repair. The lipid hydroperoxides that are obtained by lipid peroxidation of polysaturated or unsaturated fatty acids bring about deterioration of biological membranes at cellular and tissue levels. Acid phosphatase and lipid peroxidation activities were studied on the lens epithelial cells of nuclear cataract, posterior subcapsular cataract, mature cataract, and mixed cataract. Of these, mature cataractous lens epithelium showed maximum activity for acid phosphatase (516.83 moles of p-nitrophenol released/g lens epithelium and maximum levels of lipid peroxidation (86.29 O.D./min/g lens epithelium. In contrast, mixed cataractous lens epithelium showed minimum activity of acid phosphatase (222.61 moles of p-nitrophenol released/g lens epithelium and minimum levels of lipid peroxidation (54.23 O.D./min/g lens epithelium. From our study, we correlated the maximum activity of acid phosphatase in mature cataractous lens epithelium with the increased areas of superimposed cells associated with the formation of mature cataract. Likewise, the maximum levels of lipid peroxidation in mature cataractous lens epithelium was correlated with increased permeability of the plasma membrane. Conversely, the minimum levels of lipid peroxidation in mixed cataractous lens epithelium makes us presume that factors other than lipid peroxidation may also account for the formation of mixed type of cataract.

Clinical review: Management of difficult airways

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Langeron, Olivier; Amour, Julien; Vivien, Benoît; Aubrun, Frédéric

2006-01-01

Difficulties or failure in airway management are still important factors in morbidity and mortality related to anesthesia and intensive care. A patent and secure airway is essential to manage anesthetized or critically ill patients. Oxygenation maintenance during tracheal intubation is the cornerstone of difficult airway management and is always emphasized in guidelines. The occurrence of respiratory adverse events has decreased in claims for injuries due to inadequate airway management mainly at induction of anesthesia. Nevertheless, claim reports emphasize that airway emergencies, tracheal extubation and/or recovery of anesthesia phases are still associated with death or brain damage, indicating that additional educational support and management strategies to improve patient safety are required. The present brief review analyses specific problems of airway management related to difficult tracheal intubation and to difficult mask ventilation prediction. The review will focus on basic airway management including preoxygenation, and on some oxygenation and tracheal intubation techniques that may be performed to solve a difficult airway. PMID:17184555

Clinical review: management of difficult airways.

Science.gov (United States)

Langeron, Olivier; Amour, Julien; Vivien, Benoît; Aubrun, Frédéric

2006-01-01

Difficulties or failure in airway management are still important factors in morbidity and mortality related to anesthesia and intensive care. A patent and secure airway is essential to manage anesthetized or critically ill patients. Oxygenation maintenance during tracheal intubation is the cornerstone of difficult airway management and is always emphasized in guidelines. The occurrence of respiratory adverse events has decreased in claims for injuries due to inadequate airway management mainly at induction of anesthesia. Nevertheless, claim reports emphasize that airway emergencies, tracheal extubation and/or recovery of anesthesia phases are still associated with death or brain damage, indicating that additional educational support and management strategies to improve patient safety are required. The present brief review analyses specific problems of airway management related to difficult tracheal intubation and to difficult mask ventilation prediction. The review will focus on basic airway management including preoxygenation, and on some oxygenation and tracheal intubation techniques that may be performed to solve a difficult airway.

Alterations in Bronchial Airway miRNA Expression for Lung Cancer Detection.

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Pavel, Ana B; Campbell, Joshua D; Liu, Gang; Elashoff, David; Dubinett, Steven; Smith, Kate; Whitney, Duncan; Lenburg, Marc E; Spira, Avrum

2017-11-01

We have previously shown that gene expression alterations in normal-appearing bronchial epithelial cells can serve as a lung cancer detection biomarker in smokers. Given that miRNAs regulate airway gene expression responses to smoking, we evaluated whether miRNA expression is also altered in the bronchial epithelium of smokers with lung cancer. Using epithelial brushings from the mainstem bronchus of patients undergoing bronchoscopy for suspected lung cancer (as part of the AEGIS-1/2 clinical trials), we profiled miRNA expression via small-RNA sequencing from 347 current and former smokers for which gene expression data were also available. Patients were followed for one year postbronchoscopy until a final diagnosis of lung cancer ( n = 194) or benign disease ( n = 153) was made. Following removal of 6 low-quality samples, we used 138 patients (AEGIS-1) as a discovery set to identify four miRNAs (miR-146a-5p, miR-324-5p, miR-223-3p, and miR-223-5p) that were downregulated in the bronchial airway of lung cancer patients (ANOVA P cancer patients (GSEA FDR lung cancer significantly improves its performance (AUC) in the 203 samples (AEGIS-1/2) serving an independent test set (DeLong P lung cancer, and that they may regulate cancer-associated gene expression differences. Cancer Prev Res; 10(11); 651-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Response of Differentiated Human Airway Epithelia to Alcohol Exposure and Klebsiella pneumoniae Challenge

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Sammeta V. Raju

2013-07-01

Full Text Available Alcohol abuse has been associated with increased susceptibility to pulmonary infection. It is not fully defined how alcohol contributes to the host defense compromise. Here primary human airway epithelial cells were cultured at an air-liquid interface to form a differentiated and polarized epithelium. This unique culture model allowed us to closely mimic lung infection in the context of alcohol abuse by basolateral alcohol exposure and apical live bacterial challenge. Application of clinically relevant concentrations of alcohol for 24 h did not significantly alter epithelial integrity or barrier function. When apically challenged with viable Klebsiella pneumoniae, the cultured epithelia had an enhanced tightness which was unaffected by alcohol. Further, alcohol enhanced apical bacterial growth, but not bacterial binding to the cells. The cultured epithelium in the absence of any treatment or stimulation had a base-level IL-6 and IL-8 secretion. Apical bacterial challenge significantly elevated the basolateral secretion of inflammatory cytokines including IL-2, IL-4, IL-6, IL-8, IFN-γ, GM-CSF, and TNF-α. However, alcohol suppressed the observed cytokine burst in response to infection. Addition of adenosine receptor agonists negated the suppression of IL-6 and TNF-α. Thus, acute alcohol alters the epithelial cytokine response to infection, which can be partially mitigated by adenosine receptor agonists.

Upper airway segmentation and dimensions estimation from cone-beam CT image datasets

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Shi, Hongjian; Scarfe, W.C. [Louisville Univ., KY (United States). School of Dentistry; Farman, A.G. [Louisville Univ., KY (United States). School of Dentistry; Louisville Univ., KY (United States). Div. of Radiology and Imaging Science

2006-11-15

Objective: To segment and measure the upper airway using cone-beam computed tomography (CBCT). This information may be useful as an imaging biomarker in the diagnostic assessment of patients with obstructive sleep apnea and in the planning of any necessary therapy. Methods: With Institutional Review Board Approval, anonymous CBCT datasets from subjects who had been imaged for a variety of conditions unrelated to the airway were evaluated. DICOM images were available. A segmentation algorithm was developed to separate the bounded upper airway and measurements were performed manually to determine the smallest cross-sectional area and the anteriorposterior distance of the retropalatal space (RP-SCA and RP-AP, respectively) and retroglossal space (RG-SCA and RG-AP, respectively). A segmentation algorithm was developed to separate the bounded upper airway and it was applied to determine RP-AP, RG-AP, the smallest transaxial-sectional area (TSCA) and largest sagittal view airway area (LCSA). A second algorithm was created to evaluate the airway volume within this bounded upper airway. Results: Measurements of the airway segmented automatically by the developed algorithm agreed with those obtained using manual segmentation. The corresponding volumes showed only very small differences considered clinically insignificant. Conclusion: Automatic segmentation of the airway imaged using CBCT is feasible and this method can be used to evaluate airway cross-section and volume comparable to measurements extracted using manual segmentation. (orig.)

Transport across the choroid plexus epithelium.

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Praetorius, Jeppe; Damkier, Helle Hasager

2017-06-01

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

Vessel-guided airway tree segmentation

DEFF Research Database (Denmark)

Lo, Pechin Chien Pau; Sporring, Jon; Ashraf, Haseem

2010-01-01

This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. We propose a voxel classification approach for the appearance model, which uses a classifier that is trained to di...

Critical Airway Team: A Retrospective Study of an Airway Response System in a Pediatric Hospital.

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Sterrett, Emily C; Myer, Charles M; Oehler, Jennifer; Das, Bobby; Kerrey, Benjamin T

2017-12-01

Objective Study the performance of a pediatric critical airway response team. Study Design Case series with chart review. Setting Freestanding academic children's hospital. Subjects and Methods A structured review of the electronic medical record was conducted for all activations of the critical airway team. Characteristics of the activations and patients are reported using descriptive statistics. Activation of the critical airway team occurred 196 times in 46 months (March 2012 to December 2015); complete data were available for 162 activations (83%). For 49 activations (30%), patients had diagnoses associated with difficult intubation; 45 (28%) had a history of difficult laryngoscopy. Results Activation occurred at least 4 times per month on average (vs 3 per month for hospital-wide codes). The most common reasons for team activation were anticipated difficult intubation (45%) or failed intubation attempt (20%). For 79% of activations, the team performed an airway procedure, most commonly direct laryngoscopy and tracheal intubation. Bronchoscopy was performed in 47% of activations. Surgical airway rescue was attempted 4 times. Cardiopulmonary resuscitation occurred in 41 activations (25%). Twenty-nine patients died during or following team activation (18%), including 10 deaths associated with the critical airway event. Conclusion Critical airway team activation occurred at least once per week on average. Direct laryngoscopy, tracheal intubation, and bronchoscopic procedures were performed frequently; surgical airway rescue was rare. Most patients had existing risk factors for difficult intubation. Given our rate of serious morbidity and mortality, primary prevention of critical airway events will be a focus of future efforts.

Intestinal epithelium in inflammatory bowel disease

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Coskun, Mehmet

2014-01-01

The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... of inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....

Relationship between airway colonization, inflammation and exacerbation frequency in COPD.

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Tumkaya, Munir; Atis, Sibel; Ozge, Cengiz; Delialioglu, Nuran; Polat, Gurbuz; Kanik, Arzu

2007-04-01

To evaluate bacterial colonization and the airway inflammatory response, and its relationship to the frequency of exacerbation in patients with stable chronic obstructive pulmonary disease (COPD). Quantitative bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls (10 smokers and 8 non-smokers). BAL revealed the microorganisms with potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in 68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40% of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF-alpha levels were found to be significantly higher in COPD as compared to controls (P=0.001). However, only IL-8 level was significantly higher in COPD patients with frequent exacerbation as compared to infrequent (P=0.001). Airway bacterial load correlated with levels of airway inflammation markers in COPD (P<0.05). The bacterial load and airway inflammation contributes to each other in stable COPD. However, there is a link only between interleukine (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial colonization, airway inflammation and frequent exacerbations is of major importance in understanding of the COPD pathogenesis.

The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.

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Sonia R Rosner

Full Text Available Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.

Hair cell regeneration in the avian auditory epithelium.

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Stone, Jennifer S; Cotanche, Douglas A

2007-01-01

Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without dividing. In the chicken auditory epithelium, these two distinct mechanisms show unique spatial and temporal patterns, suggesting they are differentially regulated. Current efforts are aimed at identifying signals that maintain supporting cells in a quiescent state or direct them to undergo direct transdifferentiation or cell division. Here, we review current knowledge about supporting cell properties and discuss candidate signaling molecules for regulating supporting cell behavior, in quiescence and after damage. While significant advances have been made in understanding regeneration in non-mammals over the last 20 years, we have yet to determine why the mammalian auditory epithelium lacks the ability to regenerate hair cells spontaneously and whether it is even capable of significant regeneration under additional circumstances. The continued study of mechanisms controlling regeneration in the avian auditory epithelium may lead to strategies for inducing

Regional aerosol deposition in human upper airways

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Swift, D.L.

1992-11-01

Laboratory experimental studies were carried out to investigate the factors influencing the deposition of aerosols ranging in size from 1 nm to 10 [mu]m in the human nasal, oral, pharyngeal and laryngeal airways. These experimental studies were performed in replicate upper airway physical models and in human volunteer subjects. New replicate models of the oral passage of an infant, the oral passage of an adult at two openings and the combined nasal and oral airways of an adult were constructed during the period, adding to the existing models of adult, child and infant nasal and oral airways models. Deposition studies in the adult oral and adult nasal models were performed under simulated cyclic flow conditions with 1 nm particles to compare with previously measured constant flow studies. Similar studies with inertial particles (1--10 [mu]m diameter) were performed with the adult nasal model; in both instances, results with cyclic flow were similar to constant flow results using a simple average flow rate based on inspiratory volume and time of inspiration. Human subject studies were performed with particle sizes 5--20 nm for nasal inspiration; preliminary analysis shows good agreement with model studies at several representative flow rates. Nasal inspiratory inertial deposition of 1--4 [mu]m diameter particles was measured in several adults as a function of airway dimensions; dimensional changes of the valve area by decongestion did not produce concomitant deposition changes.

Bat airway epithelial cells: a novel tool for the study of zoonotic viruses.

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Isabella Eckerle

Full Text Available Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, Carollia perspicillata (Seba's short-tailed bat and Eidolon helvum (Straw-colored fruit bat, were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.

PPARγ as a Potential Target to Treat Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases

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Yongchun Shen

2012-01-01

Full Text Available Airway mucus hypersecretion (AMH is a key pathophysiological feature of chronic airway inflammatory diseases such as bronchial asthma, cystic fibrosis, and chronic obstructive pulmonary disease. AMH contributes to the pathogenesis of chronic airway inflammatory diseases, and it is associated with reduced lung function and high rates of hospitalization and mortality. It has been suggested that AMH should be a target in the treatment of chronic airway inflammatory diseases. Recent evidence suggests that a key regulator of airway inflammation, hyperresponsiveness, and remodeling is peroxisome proliferator-activated receptor gamma (PPARγ, a ligand-activated transcription factor that regulates adipocyte differentiation and lipid metabolism. PPARγ is expressed in structural, immune, and inflammatory cells in the lung. PPARγ is involved in mucin production, and PPARγ agonists can inhibit mucin synthesis both in vitro and in vivo. These findings suggest that PPARγ is a novel target in the treatment of AMH and that further work on this transcription factor may lead to new therapies for chronic airway inflammatory diseases.

Obstetric airway management

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of stomach contents into the lungs during obstetric anesthesia.8 ... Both of the mortalities occurred secondary to solid ... The large number of deaths ... subcategories of patients as a first-line airway device, and are increasingly being ... outline the problems with obstetric airway management, and then focus on a few of the ...

Ultrastructure of respiratory tract epithelium following irradiation or application of cytostatics

International Nuclear Information System (INIS)

Konradova, V.; Smelhaus, V.; Kanta, J.

1988-01-01

The ultrastructure was studied of the large bronchi epithelium in 3 patients with malignant tumors where signs of pulmonary fibrosis were found following irradiation and combined therapy. In 2 patients, pseudostratified cylindrical epithelium was observed with signs of pathological alteration, in the third patient an altered pseudostratified cylindrical epithelium with ultrastructural signs of commencing reconstructure into stratified squamous epithelium. The findings in the respiratory track epithelium of the patients were similar to those observed in a group of children with chronic or relapsing bronchitis and bronchopneumonia. The findings show marked disturbance of the ciliary border caused by reduction in the number of kinocilia which is associated with an impairment of the self-cleaning capacity of epithelium. (author). 1 tab., 10 refs

Increased airway reactivity in a neonatal mouse model of Continuous Positive Airway Pressure (CPAP)

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Mayer, Catherine A.; Martin, Richard J.; MacFarlane, Peter M.

2015-01-01

Background Continuous positive airway pressure (CPAP) is a primary form of respiratory support used in the intensive care of preterm infants, but its long-term effects on airway (AW) function are unknown. Methods We developed a neonatal mouse model of CPAP treatment to determine whether it modifies later AW reactivity. Un-anesthetized spontaneously breathing mice were fitted with a mask to deliver CPAP (6cmH2O, 3hrs/day) for 7 consecutive days starting at postnatal day 1. Airway reactivity to methacholine was assessed using the in vitro living lung slice preparation. Results One week of CPAP increased AW responsiveness to methacholine in male, but not female mice, compared to untreated control animals. The AW hyper-reactivity of male mice persisted for 2 weeks (at P21) after CPAP treatment ended. 4 days of CPAP, however, did not significantly increase AW reactivity. Females also exhibited AW hyper-reactivity at P21, suggesting a delayed response to early (7 days) CPAP treatment. The effects of 7 days of CPAP on hyper-reactivity to methacholine were unique to smaller AWs whereas larger ones were relatively unaffected. Conclusion These data may be important to our understanding of the potential long-term consequences of neonatal CPAP therapy used in the intensive care of preterm infants. PMID:25950451

Developmental origin of the posterior pigmented epithelium of iris.

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Wang, Xiaobing; Xiong, Kai; Lu, Lei; Gu, Dandan; Wang, Songtao; Chen, Jing; Xiao, Honglei; Zhou, Guomin

2015-03-01

Iris epithelium is a double-layered pigmented cuboidal epithelium. According to the current model, the neural retina and the posterior iris pigment epithelium (IPE) are derived from the inner wall of the optic cup, while the retinal pigment epithelium (RPE) and the anterior IPE are derived from the outer wall of the optic cup during development. Our current study shows evidence, contradicting this model of fetal iris development. We demonstrate that human fetal iris expression patterns of Otx2 and Mitf transcription factors are similar, while the expressions of Otx2 and Sox2 are complementary. Furthermore, IPE and RPE exhibit identical morphologic development during the early embryonic period. Our results suggest that the outer layer of the optic cup forms two layers of the iris epithelium, and the posterior IPE is the inward-curling anterior rim of the outer layer of the optic cup. These findings provide a reasonable explanation of how IPE cells can be used as an appropriate substitute for RPE cells.

Chemical composition modulates the adverse effects of particles on the mucociliary epithelium

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Regiani Carvalho-Oliveira

2015-10-01

Full Text Available OBJECTIVE:We compared the adverse effects of two types of real ambient particles; i.e., total suspended particles from an electrostatic precipitator of a steel mill and fine air particles from an urban ambient particulate matter of 2.5 µm, on mucociliary clearance.METHOD:Mucociliary function was quantified by mucociliary transport, ciliary beating frequency and the amount of acid and neutral mucous in epithelial cells through morphometry of frog palate preparations. The palates were immersed in one of the following solutions: total suspended particles (0.1 mg/mL, particulate matter 2.5 µm 0.1 mg/mL (PM0.1 or 3.0 mg/mL (PM3.0 and amphibian Ringer’s solution (control. Particle chemical compositions were determined by X-ray fluorescence and gas chromatography/mass spectrometry.RESULTS:Exposure to total suspended particles and PM3.0 decreased mucociliary transport. Ciliary beating frequency was diminished by total suspended particles at all times during exposure, while particulate matter of 2.5 µm did not elicit changes. Particulate matter of 2.5 µm reduced epithelial mucous and epithelium thickness, while total suspended particles behaved similarly to the control group. Total suspended particles exhibited a predominance of Fe and no organic compounds, while the particulate matter 2.5 µm contained predominant amounts of S, Fe, Si and, to a lesser extent, Cu, Ni, V, Zn and organic compounds.CONCLUSION:Our results showed that different compositions of particles induced different airway epithelial responses, emphasizing that knowledge of their individual characteristics may help to establish policies aimed at controlling air pollution.

Mediators on human airway smooth muscle.

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Armour, C; Johnson, P; Anticevich, S; Ammit, A; McKay, K; Hughes, M; Black, J

1997-01-01

1. Bronchial hyperresponsiveness in asthma may be due to several abnormalities, but must include alterations in the airway smooth muscle responsiveness and/or volume. 2. Increased responsiveness of airway smooth muscle in vitro can be induced by certain inflammatory cell products and by induction of sensitization (atopy). 3. Increased airway smooth muscle growth can also be induced by inflammatory cell products and atopic serum. 4. Mast cell numbers are increased in the airways of asthmatics and, in our studies, in airway smooth muscle that is sensitized and hyperresponsive. 5. We propose that there is a relationship between mast cells and airway smooth muscle cells which, once an allergic process has been initiated, results in the development of critical features in the lungs in asthma.

Hyperopic correction: clinical validation with epithelium-on and epithelium-off protocols, using variable fluence and topographically customized collagen corneal crosslinking

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Kanellopoulos AJ

2014-12-01

Full Text Available Anastasios John Kanellopoulos,1,2 George Asimellis1 1LaserViison.gr Clinical and Research Eye Institute, Athens, Greece; 2Department of Ophthalmology, New York University Medical School, New York, NY, USAPurpose: To report novel application of topographically-customized collagen crosslinking aiming to achieve hyperopic refractive changes. Two approaches were evaluated, one based on epithelium-off and one based on epithelium-on (transepithelial. Methods: A peripheral annular-shaped topographically customizable design was employed for high-fluence ultraviolet (UV-A irradiation aiming to achieve hyperopic refractive changes. A total of ten eyes were involved in this study. In group-A (five eyes, a customizable ring pattern was employed to debride the epithelium by excimer laser ablation, while in group-B (also five eyes, the epithelium remained intact. In both groups, specially formulated riboflavin solutions were applied. Visual acuity, cornea clarity, keratometry, topography, and pachymetry with a multitude of modalities, as well as endothelial cell counts were evaluated. Results: One year postoperatively, the following changes have been noted: in group-A, average uncorrected distance visual acuity changed from 20/63 to 20/40. A mean hyperopic refractive increase of +0.75 D was achieved. There was some mild reduction in the epithelial thickness. In group-B, average uncorrected distance visual acuity changed from 20/70 to 20/50. A mean hyperopic refractive increase of +0.85 D was achieved. Epithelial thickness returned to slightly reduced levels (compared to baseline in group-A, whereas to slightly increased levels in group-B. Conclusion: We introduce herein the novel application of a topographically-customizable collagen crosslinking to achieve a hyperopic refractive effect. This novel technique may be applied either with epithelial removal, offering a more stable result or with a non-ablative and non-incisional approach, offering a minimally

Development and Analysis of Patient-Based Complete Conducting Airways Models.

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Rafel Bordas

Full Text Available The analysis of high-resolution computed tomography (CT images of the lung is dependent on inter-subject differences in airway geometry. The application of computational models in understanding the significance of these differences has previously been shown to be a useful tool in biomedical research. Studies using image-based geometries alone are limited to the analysis of the central airways, down to generation 6-10, as other airways are not visible on high-resolution CT. However, airways distal to this, often termed the small airways, are known to play a crucial role in common airway diseases such as asthma and chronic obstructive pulmonary disease (COPD. Other studies have incorporated an algorithmic approach to extrapolate CT segmented airways in order to obtain a complete conducting airway tree down to the level of the acinus. These models have typically been used for mechanistic studies, but also have the potential to be used in a patient-specific setting. In the current study, an image analysis and modelling pipeline was developed and applied to a number of healthy (n = 11 and asthmatic (n = 24 CT patient scans to produce complete patient-based airway models to the acinar level (mean terminal generation 15.8 ± 0.47. The resulting models are analysed in terms of morphometric properties and seen to be consistent with previous work. A number of global clinical lung function measures are compared to resistance predictions in the models to assess their suitability for use in a patient-specific setting. We show a significant difference (p < 0.01 in airways resistance at all tested flow rates in complete airway trees built using CT data from severe asthmatics (GINA 3-5 versus healthy subjects. Further, model predictions of airways resistance at all flow rates are shown to correlate with patient forced expiratory volume in one second (FEV1 (Spearman ρ = -0.65, p < 0.001 and, at low flow rates (0.00017 L/s, FEV1 over forced vital capacity (FEV1

Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

Energy Technology Data Exchange (ETDEWEB)

Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

2016-09-30

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

Mechanical interactions between adjacent airways in the lung.

Science.gov (United States)

Ma, Baoshun; Bates, Jason H T

2014-03-15

The forces of mechanical interdependence between the airways and the parenchyma in the lung are powerful modulators of airways responsiveness. Little is known, however, about the extent to which adjacent airways affect each other's ability to narrow due to distortional forces generated within the intervening parenchyma. We developed a two-dimensional computational model of two airways embedded in parenchyma. The parenchyma itself was modeled in three ways: 1) as a network of hexagonally arranged springs, 2) as a network of triangularly arranged springs, and 3) as an elastic continuum. In all cases, we determined how the narrowing of one airway was affected when the other airway was relaxed vs. when it narrowed to the same extent as the first airway. For the continuum and triangular network models, interactions between airways were negligible unless the airways lay within about two relaxed diameters of each other, but even at this distance the interactions were small. By contrast, the hexagonal spring network model predicted that airway-airway interactions mediated by the parenchyma can be substantial for any degree of airway separation at intermediate values of airway contraction forces. Evidence to date suggests that the parenchyma may be better represented by the continuum model, which suggests that the parenchyma does not mediate significant interactions between narrowing airways.

A hybrid method for airway segmentation and automated measurement of bronchial wall thickness on CT.

Science.gov (United States)

Xu, Ziyue; Bagci, Ulas; Foster, Brent; Mansoor, Awais; Udupa, Jayaram K; Mollura, Daniel J

2015-08-01

Inflammatory and infectious lung diseases commonly involve bronchial airway structures and morphology, and these abnormalities are often analyzed non-invasively through high resolution computed tomography (CT) scans. Assessing airway wall surfaces and the lumen are of great importance for diagnosing pulmonary diseases. However, obtaining high accuracy from a complete 3-D airway tree structure can be quite challenging. The airway tree structure has spiculated shapes with multiple branches and bifurcation points as opposed to solid single organ or tumor segmentation tasks in other applications, hence, it is complex for manual segmentation as compared with other tasks. For computerized methods, a fundamental challenge in airway tree segmentation is the highly variable intensity levels in the lumen area, which often causes a segmentation method to leak into adjacent lung parenchyma through blurred airway walls or soft boundaries. Moreover, outer wall definition can be difficult due to similar intensities of the airway walls and nearby structures such as vessels. In this paper, we propose a computational framework to accurately quantify airways through (i) a novel hybrid approach for precise segmentation of the lumen, and (ii) two novel methods (a spatially constrained Markov random walk method (pseudo 3-D) and a relative fuzzy connectedness method (3-D)) to estimate the airway wall thickness. We evaluate the performance of our proposed methods in comparison with mostly used algorithms using human chest CT images. Our results demonstrate that, on publicly available data sets and using standard evaluation criteria, the proposed airway segmentation method is accurate and efficient as compared with the state-of-the-art methods, and the airway wall estimation algorithms identified the inner and outer airway surfaces more accurately than the most widely applied methods, namely full width at half maximum and phase congruency. Copyright © 2015. Published by Elsevier B.V.

CT quantification of central airway in tracheobronchomalacia

Energy Technology Data Exchange (ETDEWEB)

Im, Won Hyeong; Jin, Gong Yong; Han, Young Min; Kim, Eun Young [Dept. of Radiology, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

2016-05-15

To know which factors help to diagnose tracheobronchomalacia (TBM) using CT quantification of central airway. From April 2013 to July 2014, 19 patients (68.0 ± 15.0 years; 6 male, 13 female) were diagnosed as TBM on CT. As case-matching, 38 normal subjects (65.5 ± 21.5 years; 6 male, 13 female) were selected. All 57 subjects underwent CT with end-inspiration and end-expiration. Airway parameters of trachea and both main bronchus were assessed using software (VIDA diagnostic). Airway parameters of TBM patients and normal subjects were compared using the Student t-test. In expiration, both wall perimeter and wall thickness in TBM patients were significantly smaller than normal subjects (wall perimeter: trachea, 43.97 mm vs. 49.04 mm, p = 0.020; right main bronchus, 33.52 mm vs. 42.69 mm, p < 0.001; left main bronchus, 26.76 mm vs. 31.88 mm, p = 0.012; wall thickness: trachea, 1.89 mm vs. 2.22 mm, p = 0.017; right main bronchus, 1.64 mm vs. 1.83 mm, p = 0.021; left main bronchus, 1.61 mm vs. 1.75 mm, p = 0.016). Wall thinning and decreased perimeter of central airway of expiration by CT quantification would be a new diagnostic indicators in TBM.

Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients

DEFF Research Database (Denmark)

Porsbjerg, C.; Brannan, J.D.; Anderson, S.D.

2008-01-01

Background Airway hyperresponsiveness (AHR) to stimuli that cause bronchial smooth muscle (BSM) contraction indirectly through the release of endogenous mediators is thought to reflect air-way inflammation more closely compared with AHR measured by stimuli that act directly on BSM. Methods Fifty......, there was a stronger correlation between AHR to mannitol and the level of eNO [PD15 to mannitol vs. eNO (p.p.b.): r: -0.63, P

Airway Clearance Techniques (ACTs)

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Full Text Available ... specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway ... on their own. Share Facebook Twitter Email More options Print Share Facebook Twitter Email Print Permalink All ...

Airway Clearance Techniques (ACTs)

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Full Text Available ... Physical Therapy Coughing and Huffing High-Frequency Chest Wall Oscillation Positive Expiratory Pressure Clinical Trials Clinical Trials ... clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to ...

Airway Clearance Techniques (ACTs)

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Full Text Available ... D Structure Consortium CFTR Folding Consortium Epithelial Stem Cell Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH ... clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to ...

Airway Clearance Techniques (ACTs)

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Full Text Available ... ACTs involve coughing or huffing . Many of them use percussion (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

Airway Clearance Techniques (ACTs)

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Full Text Available ... today. ANNUAL FUND Become a Corporate Supporter Cause Marketing Make a Charitable Gift Our Corporate Supporters Workplace ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

Airway Clearance Techniques (ACTs)

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Full Text Available ... a range of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage ... LEGACY GIFT Sponsor a Participant CF Climb CF Cycle for Life Great Strides Xtreme Hike Participate In ...

Clinical review: Management of difficult airways

OpenAIRE

Langeron, Olivier; Amour, Julien; Vivien, Benoît; Aubrun, Frédéric

2006-01-01

Difficulties or failure in airway management are still important factors in morbidity and mortality related to anesthesia and intensive care. A patent and secure airway is essential to manage anesthetized or critically ill patients. Oxygenation maintenance during tracheal intubation is the cornerstone of difficult airway management and is always emphasized in guidelines. The occurrence of respiratory adverse events has decreased in claims for injuries due to inadequate airway management mainl...

Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift valley fever virus in human small airway epithelial cells.

Directory of Open Access Journals (Sweden)

Taissia G Popova

Full Text Available Rift valley fever virus (RVFV infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK and downstream transcriptional factors [STAT1 (Y701, ATF2 (T69/71, MSK1 (S360 and CREB (S133]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46 correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473, along with phosphorylation of FOX 01/03 (T24/31 which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication.

Resveratrol ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesions through effects on the epithelium

Directory of Open Access Journals (Sweden)

Sule Caglayan Sozmen

2016-03-01

Full Text Available Background. Resveratrol is a natural polyphenol that exhibits anti-inflammatory effects. The aim of this study was to investigate the effects of resveratrol treatment on epithelium-derived cytokines and epithelial apoptosis in a murine model of atopic dermatitis-like lesions. Material and Methods. Atopic dermatitis-like lesions were induced in BALB/c mice by repeated application of 2,4-dinitrofluorobenzene to shaved dorsal skin. Twenty-one BALB/c mice were divided into three groups: group I (control, group II (vehicle control, and group III (resveratrol. Systemic resveratrol (30 mg/kg/day was administered repeatedly during the 6th week of the experiment. After the mice had been sacrificed, skin tissues were examined histologically for epithelial thickness. Epithelial apoptosis (caspase-3 and epithelium-derived cytokines [interleukin (IL-25, IL-33, and thymic stromal lymphopoietin (TSLP] were evaluated immunohistochemically. Results. Epithelial thickness and the numbers of IL-25, IL-33, TSLP and caspase-3-positive cells were significantly higher in group II compared to group I mice. There was significant improvement in epithelial thickness in group III compared with group II mice (p < 0.05. The numbers of IL-25, IL-33, and TSLP-positive cells in the epithelium were lower in group III than in group II mice (p < 0.05. The number of caspase-3-positive cells, as an indicator of apoptosis, in the epithelium was significantly lower in group III than in group II mice (p < 0.05. Conclusion. Treatment with resveratrol was effective at ameliorating histological changes and inflammation by acting on epithelium-derived cytokines and epithelial apoptosis.

Airway Clearance Techniques (ACTs)

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Full Text Available ... Make a Charitable Gift Our Corporate Supporters Workplace Engagement DONATE YOUR PROPERTY eCards for a Cure About ... airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

Science.gov (United States)

Everaere, Laetitia; Ait-Yahia, Saliha; Molendi-Coste, Olivier; Vorng, Han; Quemener, Sandrine; LeVu, Pauline; Fleury, Sebastien; Bouchaert, Emmanuel; Fan, Ying; Duez, Catherine; de Nadai, Patricia; Staels, Bart; Dombrowicz, David; Tsicopoulos, Anne

2016-11-01

Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity. Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T H 2 and T H 17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T H 2 and T H 17 infiltration. These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Development of a realistic human airway model.

Science.gov (United States)

Lizal, Frantisek; Elcner, Jakub; Hopke, Philip K; Jedelsky, Jan; Jicha, Miroslav

2012-03-01

Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained.

Craniofacial and pharyngeal airway morphology in patients with acromegaly.

Science.gov (United States)

Balos Tuncer, Burcu; Canigur Bavbek, Nehir; Ozkan, Cigdem; Tuncer, Cumhur; Eroglu Altinova, Alev; Gungor, Kahraman; Akturk, Mujde; Balos Toruner, Fusun

2015-08-01

The aim of this study was to assess differences in craniofacial characteristics, upper spine and pharyngeal airway morphology in patients with acromegaly compared with healthy individuals. Twenty-one patients with acromegaly were compared with 22 controls by linear and angular measurements on cephalograms. The differences between the mean values of cephalometric parameters were analyzed with Mann-Whitney U-test. With respect to controls, anterior (pacromegaly. Craniofacial changes were predominantly found in the frontal bone (pacromegaly exhibited diminished dimensions at nasal (pacromegaly. Current results point to the importance of the reduced airway dimensions and that dentists and/or orthodontists should be aware of the cranial or dental abnormalities in patients with acromegaly.

Combined Effects of Ventilation Mode and Positive End-Expiratory Pressure on Mechanics, Gas Exchange and the Epithelium in Mice with Acute Lung Injury

Science.gov (United States)

Thammanomai, Apiradee; Hamakawa, Hiroshi; Bartolák-Suki, Erzsébet; Suki, Béla

2013-01-01

The accepted protocol to ventilate patients with acute lung injury is to use low tidal volume (VT) in combination with recruitment maneuvers or positive end-expiratory pressure (PEEP). However, an important aspect of mechanical ventilation has not been considered: the combined effects of PEEP and ventilation modes on the integrity of the epithelium. Additionally, it is implicitly assumed that the best PEEP-VT combination also protects the epithelium. We aimed to investigate the effects of ventilation mode and PEEP on respiratory mechanics, peak airway pressures and gas exchange as well as on lung surfactant and epithelial cell integrity in mice with acute lung injury. HCl-injured mice were ventilated at PEEPs of 3 and 6 cmH2O with conventional ventilation (CV), CV with intermittent large breaths (CVLB) to promote recruitment, and a new mode, variable ventilation, optimized for mice (VVN). Mechanics and gas exchange were measured during ventilation and surfactant protein (SP)-B, proSP-B and E-cadherin levels were determined from lavage and lung homogenate. PEEP had a significant effect on mechanics, gas exchange and the epithelium. The higher PEEP reduced lung collapse and improved mechanics and gas exchange but it also down regulated surfactant release and production and increased epithelial cell injury. While CVLB was better than CV, VVN outperformed CVLB in recruitment, reduced epithelial injury and, via a dynamic mechanotransduction, it also triggered increased release and production of surfactant. For long-term outcome, selection of optimal PEEP and ventilation mode may be based on balancing lung physiology with epithelial injury. PMID:23326543

Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

DEFF Research Database (Denmark)

Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

1995-01-01

Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

Airway, responsiveness and inflammation in adolescent elite swimmers

DEFF Research Database (Denmark)

Pedersen, Lise; Lund, T.K.; Barnes, P.J.

2008-01-01

Background: Whereas increased airway hyperresponsiveness (AHR) and airway inflammation are well documented in adult elite athletes, it remains uncertain whether the same airway changes are present in adolescents involved in elite sport. Objective: To investigate airway responsiveness and airway....... There was no difference in FeNO, cellular composition of sputum, airway reactivity, or prevalence of having AHR to methacholine and/or EVH between swimmers with and without respiratory symptoms. Conclusion: Adolescent elite swimmers do not have significant signs of airway damage after only a few years of intense training...... and competition. This leads us to believe that elite swimmers do not have particularly susceptible airways when they take up competitive swimming when young, but that they develop respiratory symptoms, airway inflammation, and AHR during their swimming careers Udgivelsesdato: 2008/8...

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

The operative cooperation and nursing in performing airway stent placement under DSA guidance for treating airway stenosis

International Nuclear Information System (INIS)

Yan Baojun; Wu Gang; Han Xinwei; Wang Nan; Shi Jin; Si Wenfeng; Wang Kai; Su Ning; Liu Jia; Hai Dandan

2011-01-01

Objective: To discuss the key points of the nursing care for effectively performing airway stent placement under DSA monitoring for airway stenosis. Methods: Corresponding nursing care measures were carried out for 118 patients with airway stenosis who were treated with airway stent placement. Results: The symptom of dyspnea was markedly relieved after stent implantation in all 118 patients with airway stenosis. Conclusion: To strengthen the preoperative psychological nursing and operative posture training, to make close postoperative watch on vital signs, to adopt some prevention measures for possible complications and to give necessary medical advises at the time of discharge are very helpful for patient's recovery after the surgery. (authors)

Analysis of airways in computed tomography

DEFF Research Database (Denmark)

Petersen, Jens

Chronic Obstructive Pulmonary Disease (COPD) is major cause of death and disability world-wide. It affects lung function through destruction of lung tissue known as emphysema and inflammation of airways, leading to thickened airway walls and narrowed airway lumen. Computed Tomography (CT) imaging...

A 'Good' muscle in a 'Bad' environment: the importance of airway smooth muscle force adaptation to airway hyperresponsiveness.

Science.gov (United States)

Bossé, Ynuk; Chapman, David G; Paré, Peter D; King, Gregory G; Salome, Cheryl M

2011-12-15

Asthma is characterized by airway inflammation, with a consequent increase in spasmogens, and exaggerated airway narrowing in response to stimuli, termed airway hyperresponsiveness (AHR). The nature of any relationship between inflammation and AHR is less clear. Recent ex vivo data has suggested a novel mechanism by which inflammation may lead to AHR, in which increased basal ASM-tone, due to the presence of spasmogens in the airways, may "strengthen" the ASM and ultimately lead to exaggerated airway narrowing. This phenomenon was termed "force adaptation" [Bossé, Y., Chin, L.Y., Paré, P.D., Seow, C.Y., 2009. Adaptation of airway smooth muscle to basal tone: relevance to airway hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 40, 13-18]. However, it is unknown whether the magnitude of the effect of force adaptation ex vivo could contribute to exaggerated airway narrowing in vivo. Our aim was to utilize a computational model of ASM shortening in order to quantify the potential effect of force adaptation on airway narrowing when all other mechanical factors were kept constant. The shortening in the model is dictated by a balance between physiological loads and ASM force-generating capacity at different lengths. The results suggest that the magnitude of the effect of force adaptation on ASM shortening would lead to substantially more airway narrowing during bronchial challenge at any given airway generation. We speculate that the increased basal ASM-tone in asthma, due to the presence of inflammation-derived spasmogens, produces an increase in the force-generating capacity of ASM, predisposing to AHR during subsequent challenge. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparison of the Force Required for Dislodgement Between Secured and Unsecured Airways.

Science.gov (United States)

Davenport, Curtis; Martin-Gill, Christian; Wang, Henry E; Mayrose, James; Carlson, Jestin N

2018-05-01

Airway device placement and maintenance are of utmost importance when managing critically ill patients. The best method to secure airway devices is currently unknown. We sought to determine the force required to dislodge 4 types of airways with and without airway securing devices. We performed a prospective study using 4 commonly used airway devices (endotracheal tube [ETT], laryngeal mask airway [LMA], King laryngeal tube [King], and iGel) performed on 5 different mannequin models. All devices were removed twice per mannequin in random order, once unsecured and once secured as per manufacturers' recommendations; Thomas Tube Holder (Laerdal, Stavanger, Norway) for ETT, LMA, and King; custom tube holder for iGel. A digital force measuring device was attached to the exposed end of the airway device and gradually pulled vertically and perpendicular to the mannequin until the tube had been dislodged, defined as at least 4 cm of movement. Dislodgement force was reported as the maximum force recorded during dislodgement. We compared the relative difference in the secured and unsecured force for each device and between devices using a random-effects regression model accounting for variability in the manikins. The median dislodgment forces (interquartile range [IQR]) in pounds for each secured device were: ETT 13.3 (11.6, 14.1), LMA 16.6 (13.9, 18.3), King 21.7 (16.9, 25.1), and iGel 8 (6.8, 8.3). The median dislodgement forces for each unsecured device were: ETT 4.5 (4.3, 5), LMA 8.4 (6.8, 10.7), King 10.6 (8.2, 11.5), and iGel 3.9 (3.2, 4.2). The relative difference in dislodgement forces (95% confidence intervals) were higher for each device when secured: ETT 8.6 (6.2 to 11), LMA 8.8 (4.6 to 13), King 12.1 (7.2 to 16.6), iGel 4 (1.1 to 6.9). When compared to secured ETT, the King required greater dislodgement force (relative difference 8.6 [4.5-12.7]). The secured iGel required less force than the secured ETT (relative difference -4.8 [-8.9 to -0.8]). Compared with a

Emergency surgical airway management in Denmark

DEFF Research Database (Denmark)

Rosenstock, C V; Nørskov, A K; Wetterslev, J

2016-01-01

for difficult airway management. RESULTS: In the DAD cohort 27 out of 452 461 patients had an ESA representing an incidence of 0.06 events per thousand (95% CI; 0.04 to 0.08). A total of 12 149/452 461 patients underwent Ear-Nose and Throat (ENT) surgery, giving an ESA incidence among ENT patients of 1.6 events...... of which three failed. Reviewers evaluated airway management as satisfactory in 10/27 patients. CONCLUSIONS: The incidence of ESA in the DAD cohort was 0.06 events per thousand. Among ENT patients, the ESA Incidence was 1.6 events per thousand. Airway management was evaluated as satisfactory for 10......BACKGROUND: The emergency surgical airway (ESA) is the final option in difficult airway management. We identified ESA procedures registered in the Danish Anaesthesia Database (DAD) and described the performed airway management. METHODS: We extracted a cohort of 452 461 adult patients undergoing...

Implications of Age-Related Changes in Anatomy for Geriatric-Focused Difficult Airways

Directory of Open Access Journals (Sweden)

Shih-Yi Lee

2017-09-01

Full Text Available The structure and function surrounding the airway change by the age, which may ultimately result in having anatomic features of difficult airways in the elderly. Hence, we reviewed the literature focusing on the age-related anatomic changes and accordingly to compare the characteristics of difficult airways. With age, teeth wear and loss, protein and collagen synthesis reduction, and bone loss and muscle atrophy results in aged face (chin protrusion, cheek retraction and drooping, jaw restriction (temporo-madibular joint disc displacement and osteoarthritis, neck and back stiffness, and kyphotic deformities (degeneration of spinal articular cartilage, intervertebral discs, and spinal osteoporosis. These age-related changes in anatomy are compatible with the predictors of a difficult airway. We hope that these age-related anatomic approaches will prospectively allow a detailed understanding of the hallmarks resulting in geriatric-focused difficult airways in the future studies.

Awake Craniotomy: A New Airway Approach.

Science.gov (United States)

Sivasankar, Chitra; Schlichter, Rolf A; Baranov, Dimitry; Kofke, W Andrew

2016-02-01

Awake craniotomies have been performed regularly at the University of Pennsylvania since 2004. Varying approaches to airway management are described for this procedure, including intubation with an endotracheal tube and use of a laryngeal mask airway, simple facemask, or nasal cannula. In this case series, we describe the successful use (i.e., no need for endotracheal intubation related to inadequate gas exchange) of bilateral nasopharyngeal airways in 90 patients undergoing awake craniotomies. The use of nasopharyngeal airways can ease the transition between the asleep and awake phases of the craniotomy without the need to stimulate the airway. Our purpose was to describe our experience and report adverse events related to this technique.

TRANSCRIPTOMIC ANALYSIS OF F344 RAT NASAL EPITHELIUM SUGGESTS THAT THE LACK OF CARCINOGENIC RESPONSE TO GLUTARALDEHYDE IS DUE TO ITS GREATER TOXICITY COMPARED TO FORMALDEHYDE

Science.gov (United States)

Formaldehyde is cytotoxic and carcinogenic to the rat nasal respiratory epithelium inducing tumors after 12 months. Glutaraldehyde is also cytotoxic but is not carcinogenic to nasal epithelium even after 24 months. Both aldehydes induce similar acute and subchronic histopathology...

Small airways disease: time for a revisit?

Directory of Open Access Journals (Sweden)

Stockley JA

2017-08-01

Full Text Available James A Stockley,1 Brendan G Cooper,1 Robert A Stockley,2 Elizabeth Sapey3 1Department of Lung Function and Sleep, 2Department of Respiratory Medicine, University Hospital Birmingham, 3Institute of Inflammation and Ageing, Centre for Translational Inflammation Research, University of Birmingham, Edgbaston, Birmingham, UK Abstract: It is increasingly acknowledged that delays in the diagnosis of chronic inflammatory lung conditions have hampered our understanding of pathogenesis and thus our ability to design efficacious therapies. This is particularly true for COPD, where most patients are diagnosed with moderate-to-severe airflow obstruction and little is known about the inflammatory processes present in early disease. There is great interest in developing screening tests that can identify those most at risk of developing COPD before airflow obstruction has developed for the purpose of research and clinical care. Landmark pathology studies have suggested that damage to the small airways precedes the development of airflow obstruction and emphysema and, thus, presents an opportunity to identify those at risk of COPD. However, despite a number of physiological tests being available to assess small airways function, none have been adopted into routine care in COPD. The reasons that tests of small airways have not been utilized widely include variability in test results and a lack of validated reference ranges from which to compare results for some methodologies. Furthermore, population studies have not consistently demonstrated their ability to diagnose disease. However, the landscape may be changing. As the equipment that delivers tests of small airways become more widely available, reference ranges are emerging and newer methodologies specifically seek to address variability and difficulty in test performance. Moreover, there is evidence that while tests of small airways may not be helpful across the full range of established disease severity

Polarized secretion of interleukin (IL-6 and IL-8 by human airway epithelia 16HBE14o- cells in response to cationic polypeptide challenge.

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Alison Wai-ming Chow

Full Text Available BACKGROUND: The airway epithelium participates in asthmatic inflammation in many ways. Target cells of the epithelium can respond to a variety of inflammatory mediators and cytokines. Damage to the surface epithelium occurs following the secretion of eosinophil-derived, highly toxic cationic proteins. Moreover, the surface epithelium itself is responsible for the synthesis and release of cytokines that cause the selective recruitment, retention, and accumulation of various inflammatory cells. To mimic the damage seen during asthmatic inflammation, the bronchial epithelium can be challenged with highly charged cationic polypeptides such as poly-L-arginine. METHODOLOGY/PRINCIPAL FINDINGS: In this study, human bronchial epithelial cells, 16HBE14o- cells, were "chemically injured" by exposing them to poly-l-arginine as a surrogate of the eosinophil cationic protein. Cytokine antibody array data showed that seven inflammatory mediators were elevated out of the 40 tested, including marked elevation in interleukin (IL-6 and IL-8 secretion. IL-6 and IL-8 mRNA expression levels were elevated as measured with real-time PCR. Cell culture supernatants from apical and basolateral compartments were collected, and the IL-6 and IL-8 production was quantified with ELISA. IL-6 and IL-8 secretion by 16HBE14o- epithelia into the apical compartment was significantly higher than that from the basolateral compartment. Using specific inhibitors, the production of IL-6 and IL-8 was found to be dependent on p38 MAPK, ERK1/2 MAPK, and NF-kappaB pathways. CONCLUSIONS/SIGNIFICANCE: The results clearly demonstrate that damage to the bronchial epithelia by poly-L-arginine stimulates polarized IL-6 and IL-8 secretion. This apically directed secretion of cytokines may play an important role in orchestrating epithelial cell responses to inflammation.

An examination of surface epithelium structures of the embryo across the genus Poeciliopsis (Poeciliidae).

Science.gov (United States)

Panhuis, Tami M; Fris, Megan; Tuhela, Laura; Kwan, Lucia

2017-12-01

In viviparous, teleost fish, with postfertilization maternal nutrient provisioning, embryonic structures that facilitate maternal-fetal nutrient transfer are predicted to be present. For the family Poeciliidae, only a handful of morphological studies have explored these embryonic specializations. Here, we present a comparative morphological study in the viviparous poeciliid genus, Poeciliopsis. Using microscopy techniques, we examine the embryonic surface epidermis of Poeciliopsis species that vary in their level of postfertilization maternal nutrient provisioning and placentation across two phylogenetic clades and three independent evolutionary origins of placentation. We focus on surface features of the embryo that may facilitate maternal-fetal nutrient transfer. Specifically, we studied cell apical-surface morphology associated with the superficial epithelium that covers the body and sac (yolk and pericardial) of embryos at different developmental stages. Scanning electron microscopy revealed common surface epithelial cells across species, including pavement cells with apical-surface microridges or microvilli and presumed ionocytes and/or mucus-secreting cells. For three species, in the mid-stage embryos, the surface of the body and sac were covered in microvillus epithelium. The remaining species did not display microvillus epithelium at any of the stages examined. Instead, their epithelium of the body and sac were composed of cells with apical-surface microridges. For all species, in the late stage embryos, the surface of the body proper was composed of apical-surface microridges in a "fingerprint-like arrangement." Despite the differences in the surface epithelium of embryos across Poeciliopsis species and embryonic developmental stages, this variation was not associated with the level of postfertilization maternal nutrient provisioning. We discuss these results in light of previous morphological studies of matrotrophic, teleost fish, phylogenetic

Anticholinergic treatment in airways diseases.

LENUS (Irish Health Repository)

Flynn, Robert A

2009-10-01

The prevalence of chronic airways diseases such as chronic obstructive pulmonary disease and asthma is increasing. They lead to symptoms such as a cough and shortness of breath, partially through bronchoconstriction. Inhaled anticholinergics are one of a number of treatments designed to treat bronchoconstriction in airways disease. Both short-acting and long-acting agents are now available and this review highlights their efficacy and adverse event profile in chronic airways diseases.

Changes in Upper Airway Volume Following Orthognathic Surgery.

Science.gov (United States)

Marcussen, Lillian; Stokbro, Kasper; Aagaard, Esben; Torkov, Peter; Thygesen, Torben

2017-01-01

Reduced volume of the internal skeletal dimensions of the face is 1 of the main causes of obstructive sleep apnea, and attention to patients' airways is necessary when planning orthognathic treatment. This study aims to describe changes in upper airway volume following virtually planned orthognathic surgery.A retrospective pilot study was designed with 30 randomly selected patients (10 men and 20 women, aged 23.1 ± 6.8 years, molar-relations: 15 neutral, 8 distal, and 7 mesial). Cone-beam computed tomography scans were performed before surgery and 1 week following surgery. The authors did total upper airway volume measurements and obtained 1-mm slices at vertical levels in the velo-, oro-, and hypopharynx and at the smallest visible cross-section.Measurements before and after surgery were compared using Student t test.After orthognathic surgery, the minimum cross-sectional area at the vertical level increased from 83 mm ± 33 before surgery to 102 mm ± 36 after surgery (P = 0.019). In patients with neutral and distal occlusions, the minimum cross-sectional slice volume increased in 87% but in only 57% with mesial occlusion.The present findings suggest that orthognathic surgery increases upper airway volume parameters, but a few patients have continued impairment of the airways following orthognathic surgery. Further studies are needed to confirm an individual surgical planning approach that potentially could bring the minimum cross sectional area out of the risk zone.

TR146 cells grown on filters as a model of human buccal epithelium

DEFF Research Database (Denmark)

Nielsen, Hanne Mørck; Verhoef, J C; Ponec, M

1999-01-01

The aim of the present study was to characterize the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability of test substances with different molecular weights (M(w)). For this purpose, the apparent permeability (P(app)) values for mannitol...... and for fluorescein isothiocyanate (FITC)-labelled dextrans (FD) with various M(w) (4000-40000) were compared to the P(app) values obtained using porcine buccal mucosa as an in vitro model of the human buccal epithelium. The effect of 10 mM sodium glycocholate (GC) on the P(app) values was examined. To identify...

Multiscale Vessel-guided Airway Tree Segmentation

DEFF Research Database (Denmark)

Lo, Pechin Chien Pau; Sporring, Jon; de Bruijne, Marleen

2009-01-01

This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. The method uses a voxel classification based appearance model, which involves the use of a classifier that is trai...

Coelomic epithelium-derived cells in visceral morphogenesis.

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Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

2016-03-01

Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. © 2015 Wiley Periodicals, Inc.

Increased airway reactivity in a neonatal mouse model of Continuous Positive Airway Pressure (CPAP)

OpenAIRE

Mayer, Catherine A.; Martin, Richard J.; MacFarlane, Peter M.

2015-01-01

Background Continuous positive airway pressure (CPAP) is a primary form of respiratory support used in the intensive care of preterm infants, but its long-term effects on airway (AW) function are unknown. Methods We developed a neonatal mouse model of CPAP treatment to determine whether it modifies later AW reactivity. Un-anesthetized spontaneously breathing mice were fitted with a mask to deliver CPAP (6cmH2O, 3hrs/day) for 7 consecutive days starting at postnatal day 1. Airway reactivity to...

Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol.

Science.gov (United States)

Cancado, Jose E; Mendes, Eliana S; Arana, Johana; Horvath, Gabor; Monzon, Maria E; Salathe, Matthias; Wanner, Adam

2015-04-02

In vitro and animal experiments have shown that the transport and signaling of β2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic β2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway. Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (ΔQ̇aw) were assessed. Mean ± SE EBC pH (units) and ΔQ̇aw (μl.min(-1).mL(-1)) were 6.4 ± 0.1 and 16.8 ± 1.9 during quiet breathing, 6.3 ± 0.1 and 14.5 ± 2.4 during eucapnic hyperventilation, 6.6 ± 0.2 and -0.2 ± 1.8 during hypocapnic hyperventilation (p = 0.02 and <0.01 vs. quiet breathing), and 5.9 ± 0.1 and 2.0 ± 1.5 during hypercapnic hyperventilation (p = 0.02 and <0.02 vs quiet breathing). Albuterol responsiveness in the airway as assessed by ΔQ̇aw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH. Registered at clinicaltrials.gov: NCT01216748 .

Motorcycle exhaust particles induce airway inflammation and airway hyperresponsiveness in BALB/C mice.

Science.gov (United States)

Lee, Chen-Chen; Liao, Jiunn-Wang; Kang, Jaw-Jou

2004-06-01

A number of large studies have reported that environmental pollutants from fossil fuel combustion can cause deleterious effects to the immune system, resulting in an allergic reaction leading to respiratory tract damage. In this study, we investigated the effect of motorcycle exhaust particles (MEP), a major pollutant in the Taiwan urban area, on airway inflammation and airway hyperresponsiveness in laboratory animals. BALB/c mice were instilled intratracheally (i.t.) with 1.2 mg/kg and 12 mg/kg of MEP, which was collected from two-stroke motorcycle engines. The mice were exposed 3 times i.t. with MEP, and various parameters for airway inflammation and hyperresponsiveness were sequentially analyzed. We found that MEP would induce airway and pulmonary inflammation characterized by infiltration of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BALF) and inflammatory cell infiltration in lung. In addition, MEP treatment enhanced BALF interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) cytokine levels and serum IgE production. Bronchial response measured by unrestrained plethysmography with methacholine challenge showed that MEP treatment induced airway hyperresponsiveness (AHR) in BALB/c mice. The chemical components in MEP were further fractionated with organic solvents, and we found that the benzene-extracted fraction exerts a similar biological effect as seen with MEP, including airway inflammation, increased BALF IL-4, serum IgE production, and induction of AHR. In conclusion, we present evidence showing that the filter-trapped particles emitted from the unleaded-gasoline-fueled two-stroke motorcycle engine may induce proinflammatory and proallergic response profiles in the absence of exposure to allergen.

The intuitive use of laryngeal airway tools by first year medical students.

Science.gov (United States)

Bickenbach, Johannes; Schälte, Gereon; Beckers, Stefan; Fries, Michael; Derwall, Matthias; Rossaint, Rolf

2009-09-22

Providing a secured airway is of paramount importance in cardiopulmonary resuscitation. Although intubating the trachea is yet seen as gold standard, this technique is still reserved to experienced healthcare professionals. Compared to bag-valve facemask ventilation, however, the insertion of a laryngeal mask airway offers the opportunity to ventilate the patient effectively and can also be placed easily by lay responders. Obviously, it might be inserted without detailed background knowledge.The purpose of the study was to investigate the intuitive use of airway devices by first-year medical students as well as the effect of a simple, but well-directed training programme. Retention of skills was re-evaluated six months thereafter. The insertion of a LMA-Classic and a LMA-Fastrach performed by inexperienced medical students was compared in an airway model. The improvement on their performance after a training programme of overall two hours was examined afterwards. Prior to any instruction, mean time to correct placement was 55.5 +/- 29.6 s for the LMA-Classic and 38.1 +/- 24.9 s for the LMA-Fastrach. Following training, time to correct placement decreased significantly with 22.9 +/- 13.5 s for the LMA-Classic and 22.9 +/- 19.0 s for the LMA-Fastrach, respectively (p < 0.05). After six months, the results are comparable prior (55.6 +/- 29.9 vs 43.1 +/- 34.7 s) and after a further training period (23.5 +/- 13.2 vs 26.6 +/- 21.6, p < 0.05). Untrained laypersons are able to use different airway devices in a manikin and may therefore provide a secured airway even without having any detailed background knowledge about the tool. Minimal theoretical instruction and practical skill training can improve their performance significantly. However, refreshment of knowledge seems justified after six months.

CT analysis of peripheral airway and lung lesions of patients with asthma and COPD

International Nuclear Information System (INIS)

Itoh, Takayuki; Tanaka, Hiroshi; Sahara, Shin; Ohnishi, Tetsuro; Abe, Shosaku; Ueno, Kan

2002-01-01

We compared peripheral airway and lung parenchyma images among patients with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls using high-resolution CT images taken by a multidetector-row CT scanner (Aquillion, Toshiba, Japan). CT images were saved as digital image and communication (DICOM) files and %low attenuation area (LAA) (<-960 Hounsfield Unit) was calculated with the imaging software. %LAA was significantly increased in patients with COPD (p<0.0001) and smokers with stable asthma (p<0.01) as compared with healthy controls. In stable asthma, mucous plugging in the airway sometime appeared, while during asthma exacerbation small nodules and mosaic pattern of peripheral lung field appeared. Since smoker's patients with asthma have hyper-secretion of sputum due to smoking, mucous plugging and airway inflammation may easily occur and consequently air trapping may increase. In the future, image diagnosis of peripheral airway should develop for early detection of airway diseases as a non-invasive examination. On the other hand, micro focus X-ray computed tomography system (Hitachi Medico Technology Co., Japan) can display CT images closely similar to the pictures of microscopic findings and it will be a useful tool to analyze radiologic-pathologic correlations of peripheral airways and lung parenchyma. (author)

The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis

Directory of Open Access Journals (Sweden)

Raja Alyusuf

2017-01-01

Full Text Available The role of estrogen and progesterone receptors in breast cancer biology is well established. In contrast, other steroid hormones are less well studied. Glucocorticoids (GCs are known to play a role in mammary development and differentiation; thus, it is of interest to attempt to delineate their immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the distribution pattern of glucocorticoid receptors (GRs in malignant versus nonmalignant epithelium with particular emphasis on lactational epithelium. Materials and Methods. Immunohistochemistry (IHC for GRs was performed on archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52 invasive carcinomas, 21 cases with lactational change, and 23 cases showing normal mammary tissue histology. Results. Results reveal an overexpression of GRs in mammary malignant epithelium as compared to both normal and lactational groups individually and combined. GR overexpression is significantly more pronounced in HER-2-negative cancers. Discussion. This is the first study to compare GR expression in human lactating epithelium versus malignant and normal epithelium. The article discusses the literature related to the pathobiology of GCs in the breast with special emphasis on breast cancer. Conclusion. The lactational epithelium did not show overexpression of GR, while GR was overexpressed in mammary NST (ductal carcinoma, particularly HER-2-negative cancers.

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

Energy Technology Data Exchange (ETDEWEB)

Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

2016-09-01

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

Cell kinetic changes in the follicular epithelium of pig skin after irradiation with single and fractionated doses of X rays

International Nuclear Information System (INIS)

Morris, G.M.; Hopewell, J.W.

1989-01-01

Changes in cell kinetics of the follicular epithelium of the pig were studied after x-irradiation with single and fractionated doses (30 fractions/39 days) and compared with previous epidermal data. In the follicular epithelium there was an initial degenerative phase, when the rate of cell depletion was independent of radiation dose and mode of administration. Repopulation was seen between the 14th and 18th days after single doses (15 or 20 Gy) and by the 28th day after the start of irradiation with fractionated doses (52.3-80.0 Gy). The degree of cell depletion and subsequent rate of repopulation were independent of dose. The regenerative phase was characterized by an increased cell proliferation. Islands of cells with appearance similar to cells in the normal follicular epithelium, were seen 18 days after a single dose of 20 Gy and 42 days after the start of fractionated irradiation. Compared with the epidermis, the follicular epithelium exhibited considerably less evidence of damage after both single and fractionated doses. There was a lower incidence of degenerate cells and reduced levels of cell depletion in the follicular epithelium. (author)

Radio-iodination of plasma membranes of toad bladder epithelium

Energy Technology Data Exchange (ETDEWEB)

Rodriguez, H J; Edelman, I S [California Univ., San Francisco (USA). Cardiovascular Research Inst.; California Univ., San Francisco (USA). Dept. of Medicine; California Univ., San Francisco (USA). Dept. of Biochemistry and Biophysics)

1979-01-01

The present report describes high yield enzymatic radio-iodination of the apical and basal-lateral plasma membranes of toad bladder epithelium with /sup 125/I-Na, by a procedure that does not breach the functional integrity of the epithelium, as assessed by the basal and vasopressin-sensitive short-circuit current (SCC). Iodination of basal-lateral plasma membranes, at a yield comparable to that obtained with apical labelling, was attained after about 30 min of exposure of the intact bladder to the labelling solutions. Approximately 25% of the basal-lateral labeling was lost when the epithelial cells were harvested after collagenase treatment, implying that some iodination of the basement membrane had taken place. Less than 10% of iodination of the apical or basal-lateral surfaces was accounted for by lipid-labeling. Analysis of the labeled apical and basal-lateral species by enzymatic digestion and thin layer chromatography disclosed that virtually all the radioactivity was present as mono-iodotyrosine (MIT). (orig./AJ).

[Correlation between obstructive apnea syndrome and difficult airway in ENT surgery].

Science.gov (United States)

Pera, Marcia Hiray; Tardelli, Maria Angela; Novo, Neil Ferreira; Juliano, Yara; Silva, Helga Cristina Almeida da

2017-12-21

ENT patients with obstructive sleep apnea syndrome have a tendency of collapsing the upper airways in addition to anatomical obstacles. Obstructive sleep apnea syndrome is related to the increased risk of difficult airway and also increased perioperative complications. In order to identify these patients in the preoperative period, the STOP Bang questionnaire has been highlighted because it is summarized and easy to apply. Evaluate through the STOP Bang questionnaire whether patients undergoing ENT surgery with a diagnosis of obstructive sleep apnea syndrome have a higher risk of complications, particularly the occurrence of difficult airway. Measurements of anatomical parameters for difficult airway and questionnaire application for clinical prediction of obstructive sleep apnea syndrome were performed in 48 patients with a previous polysomnographic study. The sample detected difficult airway in about 18.7% of patients, all of them with obstructive sleep apnea syndrome. This group had older age, cervical circumference > 40cm, ASA II and Cormack III/IV. Patients with obstructive sleep apnea syndrome had higher body mass index, cervical circumference, and frequent apnea. In subgroup analysis, the group with severe obstructive sleep apnea syndrome showed a significantly higher SB score compared to patients without this syndrome or with a mild/moderate obstructive sleep apnea syndrome. The STOP Bang questionnaire was not able to predict difficult airway and mild obstructive sleep apnea syndrome, but it identified marked obstructive sleep apnea syndrome. All patients with difficult airway had moderate and marked obstructive sleep apnea syndrome, although this syndrome did not involve difficult airway. The variables Cormack III/IV and BMI greater than 35 Kg.m -2 were able to predict difficult airway and obstructive sleep apnea syndrome, respectively. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

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Lifescience Database Archive (English)

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File list: Unc.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Unc.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Oth.05.AllAg.Olfactory_epithelium mm9 Unclassified Others Olfactory epithelium ...SRX112960 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.05.AllAg.Olfactory_epithelium.bed ...

Efficacy of video-guided laryngoscope in airway management skills of medical students.

Science.gov (United States)

Peirovifar, Ali; Mahmoodpoor, Ata; Golzari, Samad Ej; Soleimanpour, Hassan; Eslampour, Yashar; Fattahi, Vahid

2014-10-01

Video-guided laryngoscopy, though unproven in achieving better success rates of laryngoscopy outcome and intubation, seems to provide better glottic visualization compared with direct laryngoscopy. The objective of this study was to compare the efficacy of video-guided laryngoscope (VGL) in the airway management skills of medical students. Medical students throughout their anesthesiology rotations were enrolled in this study. All students received standard training in the airway management during their course and were randomly allocated into two 20 person groups. In Group D, airway management was performed by direct laryngoscopy via Macintosh blade and in Group G intubation was performed via VGL. Time to intubation, number of laryngoscopy attempts and success rate were noted. Successful intubation was considered as the primary outcome. All data were analyzed using SPSS 16 software. Chi-square and Fisher's exact test were used for analysis of categorical variables. For analyzing continuous variables independent t-test was used. P Time to intubation was significantly less in Group G as compared to Group D (P: 0.02). Successful intubation in Group G was less frequently when compared to Group D (P: 0.66). Need for attending intervention, esophageal intubation and hypoxemic events during laryngoscopy were less in Group G; this, however, was statistically insignificant. The use of video-guided laryngoscopy improved the first attempt success rate, time to intubation, laryngoscopy attempts and airway management ability of medical students compared to direct laryngoscopy.

Limitations of airway dimension measurement on images obtained using multi-detector row computed tomography.

Directory of Open Access Journals (Sweden)

Tsuyoshi Oguma

Full Text Available OBJECTIVES: (a To assess the effects of computed tomography (CT scanners, scanning conditions, airway size, and phantom composition on airway dimension measurement and (b to investigate the limitations of accurate quantitative assessment of small airways using CT images. METHODS: An airway phantom, which was constructed using various types of material and with various tube sizes, was scanned using four CT scanner types under different conditions to calculate airway dimensions, luminal area (Ai, and the wall area percentage (WA%. To investigate the limitations of accurate airway dimension measurement, we then developed a second airway phantom with a thinner tube wall, and compared the clinical CT images of healthy subjects with the phantom images scanned using the same CT scanner. The study using clinical CT images was approved by the local ethics committee, and written informed consent was obtained from all subjects. Data were statistically analyzed using one-way ANOVA. RESULTS: Errors noted in airway dimension measurement were greater in the tube of small inner radius made of material with a high CT density and on images reconstructed by body algorithm (p<0.001, and there was some variation in error among CT scanners under different fields of view. Airway wall thickness had the maximum effect on the accuracy of measurements with all CT scanners under all scanning conditions, and the magnitude of errors for WA% and Ai varied depending on wall thickness when airways of <1.0-mm wall thickness were measured. CONCLUSIONS: The parameters of airway dimensions measured were affected by airway size, reconstruction algorithm, composition of the airway phantom, and CT scanner types. In dimension measurement of small airways with wall thickness of <1.0 mm, the accuracy of measurement according to quantitative CT parameters can decrease as the walls become thinner.

Claudin expression in follicle-associated epithelium of rat Peyer's patches defines a major restriction of the paracellular pathway.

Science.gov (United States)

Markov, A G; Falchuk, E L; Kruglova, N M; Radloff, J; Amasheh, S

2016-01-01

Members of the tight junction protein family of claudins have been demonstrated to specifically determine paracellular permeability of the intestinal epithelium. In small intestinal mucosa, which is generally considered to be a leaky epithelium, Peyer's patches are a primary part of the immune system. The aim of this study was to analyse the tight junctional barrier of follicle-associated epithelium covering Peyer's patches (lymphoid follicles). Employing small intestinal tissue specimens of male Wistar rats, electrophysiological analyses including the Ussing chamber technique, marker flux measurements and one-path impedance spectroscopy were performed. Morphometry of HE-stained tissue sections was taken into account. Claudin expression and localization was analysed by immunoblotting and confocal laser scanning immunofluorescence microscopy. Almost twofold higher parameters of epithelial and transepithelial tissue resistance and a markedly lower permeability for the paracellular permeability markers 4 and 20 kDa FITC-dextran were detected in follicle-associated epithelium compared to neighbouring villous epithelium. Analysis of claudin expression and localization revealed a stronger expression of major sealing proteins in follicle-associated epithelium, including claudin-1, claudin-4, claudin-5 and claudin-8. Therefore, the specific expression and localization of claudins is in accordance with barrier properties of follicle-associated epithelium vs. neighbouring villous epithelium. We demonstrate that follicle-associated epithelium is specialized to ensure maximum restriction of the epithelial paracellular pathway in Peyer's patches by selective sealing of tight junctions. This results in an exclusive transcellular pathway of epithelial cells as the limiting and mandatory route for a controlled presentation of antigens to the underlying lymphocytes under physiological conditions. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Post-extubation airway obstruction. Literature review

Directory of Open Access Journals (Sweden)

Álvaro SÁNCHEZ-TABERNERO

2017-03-01

Full Text Available Introduction and objective: airway obstruction after extubation in any surgery is a critical event with low incidence, which may require reintubation or tracheostomy, which often otolaryngologist is required. Objective: To determine the prevalence of BVA and its causes through systematic literature review. Method: Literature review in PubMed, Scopus and Cochrane clinical trials, meta-analysis, reviews and case series and control over airway obstruction after extubation that requires reintubation in adults. Results: 6 studies and one clinical practice guidelines were selected. The most common cause of extubation failure is blocking the airway for various reasons (pharyngeal muscle weakness residual effect -often farmacologycal-, laryngospasm, vocal cord paralysis, edema of upper respiratory tract, cervical postoperative hematoma, foreign bodies or secretions. Most cases of re-intubation occurred within 2 hours after extubation. Conclusions: The most common cause of failure after general anesthesia extubation is blocking the airway generally caused by residual neuromuscular blocking effect. Airway obstruction risk increases in airway and head and neck surgery. Difficult intubation guidlines have improved performance and reduced adverse events and similar strategies must be implemented in extubation. The procedure extubation and reintubation should be documented. Working groups airway must be multidisciplinary and include specialists in otolaryngology.

File list: DNS.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: DNS.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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Detecting airway remodeling in COPD and emphysema using low-dose CT imaging

Science.gov (United States)

Rudyanto, R.; Ceresa, M.; Muñoz-Barrutia, A.; Ortiz-de-Solorzano, C.

2012-03-01

In this study, we quantitatively characterize lung airway remodeling caused by smoking-related emphysema and Chronic Obstructive Pulmonary Disease (COPD), in low-dose CT scans. To that end, we established three groups of individuals: subjects with COPD (n=35), subjects with emphysema (n=38) and healthy smokers (n=28). All individuals underwent a low-dose CT scan, and the images were analyzed as described next. First the lung airways were segmented using a fast marching method and labeled according to its generation. Along each airway segment, cross-section images were resampled orthogonal to the airway axis. Next 128 rays were cast from the center of the airway lumen in each crosssection slice. Finally, we used an integral-based method, to measure lumen radius, wall thickness, mean wall percentage and mean peak wall attenuation on every cast ray. Our analysis shows that both the mean global wall thickness and the lumen radius of the airways of both COPD and emphysema groups were significantly different from those of the healthy group. In addition, the wall thickness change starts at the 3rd airway generation in the COPD patients compared with emphysema patients, who display the first significant changes starting in the 2nd generation. In conclusion, it is shown that airway remodeling happens in individuals suffering from either COPD or emphysema, with some local difference between both groups, and that we are able to detect and accurately quantify this process using images of low-dose CT scans.

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: Oth.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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Semi-Automatic Measurement of the Airway Dimension by Computed Tomography Using the Full-With-Half- Maximum Method: a Study of the Measurement Accuracy according to the Orientation of an Artificial Airway

International Nuclear Information System (INIS)

Kim, Nam Kug; Seo, Joon Beom; Song, Koun Sik; Chae, Eun Jin; Kang, Suk Ho

2008-01-01

To develop an algorithm to measure the dimensions of an airway oriented obliquely on a volumetric CT, as well as assess the effect of the imaging parameters on the correct measurement of the airway dimension. An airway phantom with 11 poly-acryl tubes of various lumen diameters and wall thicknesses was scanned using a 16-MDCT (multidetector CT) at various tilt angles (0, 30, 45, and 60 ). The CT images were reconstructed at various reconstruction kernels and thicknesses. The axis of each airway was determined using the 3D thinning algorithm, with images perpendicular to the axis being reconstructed. The luminal radius and wall thickness was measured by the full-width-half-maximum method. The influence of the CT parameters (the size of the airways, obliquity on the radius and wall thickness) was assessed by comparing the actual dimension of each tube with the estimated values. The 3D thinning algorithm correctly determined the axis of the oblique airway in all tubes (mean error: 0.91 ± 0.82 .deg. ). A sharper reconstruction kernel, thicker image thickness and larger tilt angle of the airway axis resulted in a significant decrease of the measured wall thickness and an increase of the measured luminal radius. Use of a standard kernel and a 0.75-mm slice thickness resulted in the most accurate measurement of airway dimension, which was independent of obliquity. The airway obliquity and imaging parameters have a strong influence on the accuracy of the airway wall measurement. For the accurate measurement of airway thickness, the CT images should be reconstructed with a standard kernel and a 0.75 mm slice thickness

File list: Pol.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: Pol.Oth.10.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Pol.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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Pharyngeal airway changes following mandibular setback surgery

Directory of Open Access Journals (Sweden)

Babu Ramesh

2005-01-01

Full Text Available Treatment of dentofacial deformities with jaw osteotomies has an effect on airway anatomy and therefore mandibular setback surgery has the potential to diminish airway size. The purpose of this study was to evaluate the effect of mandibular setback surgery on airway size. 8 consecutive patients were examined prospectively. All patients underwent mandibular setback surgery. Cephalometric analysis was performed preoperatively and 3 months post operatively with particular attention to pharyngeal airway changes. Pharyngeal airway size decreased considerably in all, patients thus predisposing to development of obstructive sleep apnea. Therefore, large anteroposterior discrepancies should be corrected by combined maxillary and mandibular osteotomies.

Expressions of TRPVs in the cholesteatoma epithelium.

Science.gov (United States)

Do, Ba Hung; Koizumi, Hiroki; Ohbuchi, Toyoaki; Kawaguchi, Rintaro; Suzuki, Hideaki

2017-10-01

We have recently proposed a hypothesis that acid leakage through the cholesteatoma epithelium mediates bone resorption in middle ear cholesteatoma. In the present study, we investigated the expressions of transient receptor potential vanilloid (TRPV) channels, which have been shown to play roles in the regulation of epidermal barrier function, in the cholesteatoma epithelium in comparison with the normal skin. Cholesteatoma epithelium and postauricular skin were collected from 17 patients with primary acquired middle ear cholesteatoma who underwent tympanomastoidectomy. Expressions of TRPV1, TRPV3, TRPV4, and TRPV6 were explored by fluorescence immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). TRPV1, TRPV3, TRPV4, and TRPV6 mRNAs were all detected by qRT-PCR both in the skin and cholesteatoma tissue. Immunohistochemical staining showed that TRPV1 and TRPV3 were positive in the viable cell layers of the epidermis of the skin, and only TRPV3 was positive in those of the cholesteatoma epithelium. The immunoreactivity for TRPV3 was significantly weaker in cholesteatoma than in the skin. The lower expression of TRPV3 in cholesteatoma may be one of the mechanisms underlying the increased permeability of this tissue. On the other hand, TRPV1, TRPV4, and TRPV6 are unlikely to be involved in the regulation of epithelial permeability in cholesteatoma.

Evaluation of airway protection: Quantitative timing measures versus penetration/aspiration score.

Science.gov (United States)

Kendall, Katherine A

2017-10-01

Quantitative measures of swallowing function may improve the reliability and accuracy of modified barium swallow (MBS) study interpretation. Quantitative study analysis has not been widely instituted, however, secondary to concerns about the time required to make measures and a lack of research demonstrating impact on MBS interpretation. This study compares the accuracy of the penetration/aspiration (PEN/ASP) scale (an observational visual-perceptual assessment tool) to quantitative measures of airway closure timing relative to the arrival of the bolus at the upper esophageal sphincter in identifying a failure of airway protection during deglutition. Retrospective review of clinical swallowing data from a university-based outpatient clinic. Swallowing data from 426 patients were reviewed. Patients with normal PEN/ASP scores were identified, and the results of quantitative airway closure timing measures for three liquid bolus sizes were evaluated. The incidence of significant airway closure delay with and without a normal PEN/ASP score was determined. Inter-rater reliability for the quantitative measures was calculated. In patients with a normal PEN/ASP score, 33% demonstrated a delay in airway closure on at least one swallow during the MBS study. There was no correlation between PEN/ASP score and airway closure delay. Inter-rater reliability for the quantitative measure of airway closure timing was nearly perfect (intraclass correlation coefficient = 0.973). The use of quantitative measures of swallowing function, in conjunction with traditional visual perceptual methods of MBS study interpretation, improves the identification of airway closure delay, and hence, potential aspiration risk, even when no penetration or aspiration is apparent on the MBS study. 4. Laryngoscope, 127:2314-2318, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Continuous Positive Airway Pressure (CPAP)

Science.gov (United States)

... ENT Doctor Near You Continuous Positive Airway Pressure (CPAP) Continuous Positive Airway Pressure (CPAP) Patient Health Information ... relations staff at newsroom@entnet.org . What Is CPAP? The most common and effective nonsurgical treatment for ...

Respiratory Epithelium Lined Cyst of the Maxilla: Differential Diagnosis

Directory of Open Access Journals (Sweden)

C. P. Martinelli-Kläy

2017-01-01

Full Text Available Maxillary cysts, including the cysts lined by respiratory epithelium, can present a diagnostic challenge. We report an unusual case of a maxillary cyst on an endodontically treated tooth #16, in which the cavity was totally lined by a respiratory epithelium. The patient, a 35-year-old male, presented with a generalized chronic periodontitis and complained of a pain in the tooth #16 region. A periodontal pocket extending to the root apices with pus coming out from the gingival was found. A combined endodontic periodontal was observed on a panoramic radiography. CBCT-scan revealed a well-circumscribed radiolucent lesion at the apices of the distobuccal root of the 16. A communication with the right maxillary sinus cavity and a maxillary and ethmoidal sinusitis were also observed. The lesion was removed and histological examination revealed a cyst lined exclusively by respiratory epithelium. Ciliated and rare mucous cells were also observed. The diagnosis could evoke a surgical ciliated cyst mimicking the radicular cyst but the patient has no previous history of trauma or surgery in the maxillofacial region. It could also be an unusual radicular cyst in which the stratified squamous epithelium was destroyed by inflammation and replaced by a respiratory epithelium of the maxillary sinus.

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: ALL.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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The Difficult Airway Society 'ADEPT' guidance on selecting airway devices: the basis of a strategy for equipment evaluation.

Science.gov (United States)

Pandit, J J; Popat, M T; Cook, T M; Wilkes, A R; Groom, P; Cooke, H; Kapila, A; O'Sullivan, E

2011-08-01

Faced with the concern that an increasing number of airway management devices were being introduced into clinical practice with little or no prior evidence of their clinical efficacy or safety, the Difficult Airway Society formed a working party (Airway Device Evaluation Project Team) to establish a process by which the airway management community within the profession could itself lead a process of formal device/equipment evaluation. Although there are several national and international regulations governing which products can come on to the market and be legitimately sold, there has hitherto been no formal professional guidance relating to how products should be selected (i.e. purchased). The Airway Device Evaluation Project Team's first task was to formulate such advice, emphasising evidence-based principles. Team discussions led to a definition of the minimum level of evidence needed to make a pragmatic decision about the purchase or selection of an airway device. The Team concluded that this definition should form the basis of a professional standard, guiding those with responsibility for selecting airway devices. We describe how widespread adoption of this professional standard can act as a driver to create an infrastructure in which the required evidence can be obtained. Essential elements are that: (i) the Difficult Airway Society facilitates a coherent national network of research-active units; and (ii) individual anaesthetists in hospital trusts play a more active role in local purchasing decisions, applying the relevant evidence and communicating their purchasing decisions to the Difficult Airway Society. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

Stenting of major airway constriction

International Nuclear Information System (INIS)

Wu Xiaomei

2002-01-01

Objective: To investigate the correlated issues in the stenting treatment of major airway constriction. Methods: Nineteen cases of major airway stenting procedure were studied retrospectively. The clinical choice of stents of different advantages or deficiencies were discussed. The importance of intravenous anesthesia supporting, life-parameters monitoring during the procedures and the prevention of complications were analysed. Results: Under intravenous and local anesthesia, 19 Wallstents had been successively placed and relieved 19 cases of major airway constrictions due to malignant or benign diseases (15 of tumors, 3 of tuberculosis, 1 of tracheomalacia). Intravenous anesthesia and life-parameters monitoring had made the procedures more safe and precise. Conclusions: Major airway stenting is an reliable method for relieving tracheobronchial stenosis; and intravenous anesthesia supporting and life-parameters monitoring guarantee the satisfactions of procedures

Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

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Mayumi Oakland

2013-01-01

Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

Role of Aquaporin Water Channels in Airway Fluid Transport, Humidification, and Surface Liquid Hydration

Science.gov (United States)

Song, Yuanlin; Jayaraman, Sujatha; Yang, Baoxue; Matthay, Michael A.; Verkman, A.S.

2001-01-01

Several aquaporin-type water channels are expressed in mammalian airways and lung: AQP1 in microvascular endothelia, AQP3 in upper airway epithelia, AQP4 in upper and lower airway epithelia, and AQP5 in alveolar epithelia. Novel quantitative methods were developed to compare airway fluid transport–related functions in wild-type mice and knockout mice deficient in these aquaporins. Lower airway humidification, measured from the moisture content of expired air during mechanical ventilation with dry air through a tracheotomy, was 54–56% efficient in wild-type mice, and reduced by only 3–4% in AQP1/AQP5 or AQP3/AQP4 double knockout mice. Upper airway humidification, measured from the moisture gained by dry air passed through the upper airways in mice breathing through a tracheotomy, decreased from 91 to 50% with increasing ventilation from 20 to 220 ml/min, and reduced by 3–5% in AQP3/AQP4 knockout mice. The depth and salt concentration of the airway surface liquid in trachea was measured in vivo using fluorescent probes and confocal and ratio imaging microscopy. Airway surface liquid depth was 45 ± 5 μm and [Na+] was 115 ± 4 mM in wild-type mice, and not significantly different in AQP3/AQP4 knockout mice. Osmotic water permeability in upper airways, measured by an in vivo instillation/sample method, was reduced by ∼40% by AQP3/AQP4 deletion. In doing these measurements, we discovered a novel amiloride-sensitive isosmolar fluid absorption process in upper airways (13% in 5 min) that was not affected by aquaporin deletion. These results establish the fluid transporting properties of mouse airways, and indicate that aquaporins play at most a minor role in airway humidification, ASL hydration, and isosmolar fluid absorption. PMID:11382807

Multislice helical CT analysis of small-sized airway wall thickness in smokers and patients with bronchial asthma

International Nuclear Information System (INIS)

Sekimura, Kenshi; Ito, Harumasa; Nakamura, Yutaka; Kobayashi, Hitoshi; Oikawa, Hirobumi; Inoue, Hiroshi; Ehara, Shigeru; Yamauchi, Kohei

2010-01-01

There is accumulating evidence that airway remodeling, which contributes to airway narrowing, plays a role in the pathogenesis of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). Development of the multislice helical CT (MSCT) with improved spatial resolution has made it possible to obtain more precise imaging of small-sized airways. Small-sized airway wall-thickness was measured using the MSCT scan to analyze small-sized airways of smokers and BA patients, and examine the effects of a β 2 agonists on small-sized airway wall-thickness of BA patients. Thirty-six non-asthmatics who participated in the Health Check Program of Iwate Medical University and 25 patients with asthma were recruited. Amongst the 36 non-asthmatics were 20 healthy never-smokers and 15 smokers. The other 25 asthmatics were recruited from the outpatient clinic at Iwate Medical University. MSCT was performed and the right B10 bronchus was chosen for dimensional analysis. Airway wall thickness was expressed as a percentage of wall area (WA%). WA% of the 7 asthmatics before and 30 mim after procaterol (20μg) inspiration were compared. Small-sized airway wall thickness was significantly increased in smokers and patients with asthma compared to healthy never-smokers, when determined by MSCT. Both %V 50 and %V 25 had significant negative correlations with WA% among the healthy never-smokers and smoker population. Procaterol inspiration reduced WA% in the small airway of patients with asthma. Increase of small-sized airway thickness measured by MSCT scan may reflect peripheral obstructive lesions of smokers and BA patients. (author)

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File list: His.Oth.50.AllAg.Olfactory_epithelium [Chip-atlas[Archive

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File list: His.Oth.20.AllAg.Olfactory_epithelium [Chip-atlas[Archive

Lifescience Database Archive (English)

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Computed tomography dose and variability of airway dimension measurements: how low can we go?

International Nuclear Information System (INIS)

Jong, Pim A. de; Long, Frederick R.; Nakano, Yasutaka

2006-01-01

Quantitative CT shows promise as an outcome measure for cystic fibrosis (CF) lung disease in infancy, but must be accomplished at a dose as low as reasonably achievable. To determine the feasibility of ultra-low-dose CT for quantitative measurements of airway dimensions. Two juvenile pigs were anesthetized and their lungs scanned at 25 cm H 2 O face-mask pressure in apnoea using beam currents of 5, 10, 20, 40 and 100 mAs. The lumen diameters and wall thicknesses of matched airways (n=22) at each dose were measured by two observers using validated software. Measurement variability at each dose was compared to that at 100 mAs (reference dose) for large and small airways (lumen diameter <2.5 mm). Lowering CT dose (mAs) affected measurement variability for lumen diameter of small and large airways (P<0.001) and for wall thickness of small (P<0.001), but not large (P=0.63), airways. To obtain the same measurement variability at 5 mAs as at 100 mAs, four to six small airways or one to three large airways have to be measured and averaged. Quantitative airway measurements are feasible on images obtained at as low as 5 mAs, but more airways need to be measured to compensate for greater measurement variability. (orig.)

The microbial community of the cystic fibrosis airway is disrupted in early life.

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Julie Renwick

Full Text Available Molecular techniques have uncovered vast numbers of organisms in the cystic fibrosis (CF airways, the clinical significance of which is yet to be determined. The aim of this study was to describe and compare the microbial communities of the lower airway of clinically stable children with CF and children without CF.Bronchoalveolar lavage (BAL fluid and paired oropharyngeal swabs from clinically stable children with CF (n = 13 and BAL from children without CF (n = 9 were collected. DNA was isolated, the 16S rRNA regions amplified, fragmented, biotinylated and hybridised to a 16S rRNA microarray. Patient medical and demographic information was recorded and standard microbiological culture was performed.A diverse bacterial community was detected in the lower airways of children with CF and children without CF. The airway microbiome of clinically stable children with CF and children without CF were significantly different as measured by Shannon's Diversity Indices (p = 0.001; t test and Principle coordinate analysis (p = 0.01; Adonis test. Overall the CF airway microbial community was more variable and had a less even distribution than the microbial community in the airways of children without CF. We highlighted several bacteria of interest, particularly Prevotella veroralis, CW040 and a Corynebacterium, which were of significantly differential abundance between the CF and non-CF lower airways. Both Pseudomonas aeruginosa and Streptococcus pneumoniae culture abundance were found to be associated with CF airway microbial community structure. The CF upper and lower airways were found to have a broadly similar microbial milieu.The microbial communities in the lower airways of stable children with CF and children without CF show significant differences in overall diversity. These discrepancies indicate a disruption of the airway microflora occurring early in life in children with CF.

Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.

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Masami Watabe-Rudolph

Full Text Available Atrophy of the olfactory epithelium (OE associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/- with short telomeres compared to wild type mice (mTerc(+/+ with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/- mice compared to mTerc(+/+ mice. Seven days after chemical induced damage, G3 mTerc(-/- mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+ mice (p = 0.031. Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21 rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people.

Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma.

Science.gov (United States)

Ogulur, Ismail; Gurhan, Gulben; Aksoy, Ayca; Duruksu, Gokhan; Inci, Cigdem; Filinte, Deniz; Kombak, Faruk Erdem; Karaoz, Erdal; Akkoc, Tunc

2014-05-01

New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (Pasthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma. Copyright © 2014 Elsevier B.V. All rights reserved.

Airway exploration in children

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Fernando GÓMEZ-SÁEZ

2018-03-01

Full Text Available Introduction and objective: The management of the airways represents a constant challenge in pediatric practice. In the last years, bronchoscopy has become an essential technique in the diagnosis and treatment of various abnormalities of the child's respiratory system. The special characteristics of the pediatric airway and the differentiated pathology it presents give pediatric bronchoscopy its own entity. Pediatric bronchoscopy is a safe technique with many applications, both diagnostic and therapeutic. The use of both types of bronchoscopes (flexible and rigid allows to take advantage of each one of them. Flexible bronchoscopy in pediatrics is a relatively simple and low-risk procedure that provides anatomical and dynamic information on the airways, as well as cytological and microbiological studies. The simplicity and low risk of this technique, in addition to not requiring general anesthesia, allows it to be performed even at the head of the patient, which has led to an increasingly extensive field of indications. The purpose of this article is to provide a review on the timeliness of the pediatric bronchoscopy procedure, especially about its indications. Method: Narrative review. Conclusion: The endoscopic examination of the airway is a cost-effective technique in pediatrics, with little complications and can offer very valuable diagnostic information, as well as perform certain therapeutic procedures. It is recommended that all professionals involved in the management of patients with airway pathology should know their indications, contraindications, complications, as well as their therapeutic applications.

[Characterization of stem cells derived from the neonatal auditory sensory epithelium].

Science.gov (United States)

Diensthuber, M; Heller, S

2010-11-01

In contrast to regenerating hair cell-bearing organs of nonmammalian vertebrates the adult mammalian organ of Corti appears to have lost its ability to maintain stem cells. The result is a lack of regenerative ability and irreversible hearing loss following auditory hair cell death. Unexpectedly, the neonatal auditory sensory epithelium has recently been shown to harbor cells with stem cell features. The origin of these cells within the cochlea's sensory epithelium is unknown. We applied a modified neurosphere assay to identify stem cells within distinct subregions of the neonatal mouse auditory sensory epithelium. Sphere cells were characterized by multiple markers and morphologic techniques. Our data reveal that both the greater and the lesser epithelial ridge contribute to the sphere-forming stem cell population derived from the auditory sensory epithelium. These self-renewing sphere cells express a variety of markers for neural and otic progenitor cells and mature inner ear cell types. Stem cells can be isolated from specific regions of the auditory sensory epithelium. The distinct features of these cells imply a potential application in the development of a cell replacement therapy to regenerate the damaged sensory epithelium.

Airway management and morbid obesity

DEFF Research Database (Denmark)

Kristensen, Michael S

2010-01-01

Morbidly obese patients present with excess fatty tissue externally on the breast, neck, thoracic wall and abdomen and internally in the mouth, pharynx and abdomen. This excess tissue tends to make access (intubation, tracheostomy) to and patency (during sedation or mask ventilation) of the upper...... in morbidly obese patients and should be followed by actions to counteract atelectasis formation. The decision as to weather to use a rapid sequence induction, an awake intubation or a standard induction with hypnotics should depend on the thorough airway examination and comorbidity and should not be based...... solely on whether morbid obesity is present or not. It is important to ensure sufficient depth of anaesthesia before initiating manipulation of the airway because inadequate anaesthesia depth predisposes to aspiration if airway management becomes difficult. The intubating laryngeal mask airway is more...

Hold your horses: A comparison of human laryngomalacia with analogous equine airway pathology.

Science.gov (United States)

Lawrence, Rachael J; Butterell, Matthew J; Constable, James D; Daniel, Matija

2018-02-01

Laryngomalacia is the most common cause of stridor in infants. Dynamic airway collapse is also a well-recognised entity in horses and an important cause of surgical veterinary intervention. We compare the aetiology, clinical features and management of human laryngomalacia with equine dynamic airway collapse. A structured review of the PubMed, the Ovid Medline and the Cochrane Collaboration databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Systemic Reviews). There are numerous equine conditions that cause dynamic airway collapse defined specifically by the anatomical structures involved. Axial Deviation of the Aryepiglottic Folds (ADAF) is the condition most clinically analogous to laryngomalacia in humans, and is likewise most prevalent in the immature equine airway. Both conditions are managed either conservatively, or if symptoms require it, with surgical intervention. The operative procedures performed for ADAF and laryngomalacia are technically comparable. Dynamic collapse of the equine larynx, especially ADAF, is clinically similar to human laryngomalacia, and both are treated in a similar fashion. Copyright © 2017 Elsevier B.V. All rights reserved.

The intuitive use of laryngeal airway tools by first year medical students

Directory of Open Access Journals (Sweden)

Fries Michael

2009-09-01

Full Text Available Abstract Background Providing a secured airway is of paramount importance in cardiopulmonary resuscitation. Although intubating the trachea is yet seen as gold standard, this technique is still reserved to experienced healthcare professionals. Compared to bag-valve facemask ventilation, however, the insertion of a laryngeal mask airway offers the opportunity to ventilate the patient effectively and can also be placed easily by lay responders. Obviously, it might be inserted without detailed background knowledge. The purpose of the study was to investigate the intuitive use of airway devices by first-year medical students as well as the effect of a simple, but well-directed training programme. Retention of skills was re-evaluated six months thereafter. Methods The insertion of a LMA-Classic and a LMA-Fastrach performed by inexperienced medical students was compared in an airway model. The improvement on their performance after a training programme of overall two hours was examined afterwards. Results Prior to any instruction, mean time to correct placement was 55.5 ± 29.6 s for the LMA-Classic and 38.1 ± 24.9 s for the LMA-Fastrach. Following training, time to correct placement decreased significantly with 22.9 ± 13.5 s for the LMA-Classic and 22.9 ± 19.0 s for the LMA-Fastrach, respectively (p Conclusion Untrained laypersons are able to use different airway devices in a manikin and may therefore provide a secured airway even without having any detailed background knowledge about the tool. Minimal theoretical instruction and practical skill training can improve their performance significantly. However, refreshment of knowledge seems justified after six months.

Rhinosinusitis and the lower airways

NARCIS (Netherlands)

Hellings, Peter W.; Hens, Greet

2009-01-01

The interaction between upper and lower airway disease has been recognized for centuries, with recent studies showing a direct link between upper and airway inflammation in allergic patients. The mechanisms underlying the interaction between nasal and bronchial inflammation have primarily been

Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

Science.gov (United States)

Ingram, Jennifer L; Slade, David; Church, Tony D; Francisco, Dave; Heck, Karissa; Sigmon, R Wesley; Ghio, Michael; Murillo, Anays; Firszt, Rafael; Lugogo, Njira L; Que, Loretta; Sunday, Mary E; Kraft, Monica

2016-01-01

Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

Are new supraglottic airway devices, tracheal tubes and airway viewing devices cost-effective?

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Slinn, Simon J; Froom, Stephen R; Stacey, Mark R W; Gildersleve, Christopher D

2015-01-01

Over the past two decades, a plethora of new airway devices has become available to the pediatric anesthetist. While all have the laudable intention of improving patient care and some have proven clinical benefits, these devices are often costly and at times claims of an advantage over current equipment and techniques are marginal. Supraglottic airway devices are used in the majority of pediatric anesthetics delivered in the U.K., and airway-viewing devices provide an alternative for routine intubation as well as an option in the management of the difficult airway. Yet hidden beneath the convenience of the former and the technology of the latter, the impact on basic airway skills with a facemask and the lack of opportunities to fine-tune the core skill of intubation represent an unrecognised and unquantifiable cost. A judgement on this value must be factored into the absolute purchase cost and any potential benefits to the quality of patient care, thus blurring any judgement on cost-effectiveness that we might have. An overall value on cost-effectiveness though not in strict monetary terms can then be ascribed. In this review, we evaluate the role of these devices in the care of the pediatric patient and attempt to balance the advantages they offer against the cost they incur, both financial and environmental, and in any quality improvement they might offer in clinical care. © 2014 John Wiley & Sons Ltd.

Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls

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Ishikawa, Nobuhisa; Hattori, Noboru; Kohno, Nobuoki; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm

2015-01-01

Purpose To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. Patients and methods This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. Results The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; Pbenefit in disease management of COPD in Japan. PMID:25670894

The importance of clinical monitoring for compliance with Continuous Positive Airway Pressure.

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Pelosi, Lucas B; Silveira, Mariana L C; Eckeli, Alan L; Chayamiti, Emilia M P C; Almeida, Leila A; Sander, Heidi H; Küpper, Daniel S; Valera, Fabiana C P

Obstructive sleep apnea syndrome is currently a public health problem of great importance. When misdiagnosed or improperly treated, it can lead to serious consequences on patients' quality of life. The gold standard treatment for cases of obstructive sleep apnea syndrome, especially in mild to severe and symptomatic cases, is continuous positive airway pressure therapy. Compliance with continuous positive airway pressure therapy is directly dependent on the active participation of the patient, which can be influenced by several factors. The objective of this study is to describe the factors related to compliance with continuous positive airway pressure therapy, and to analyze which associated factors directly influence the efficiency of the treatment. Patients who received continuous positive airway pressure therapy through the Municipal Health Department of the city of Ribeirão Preto were recruited. A structured questionnaire was administered to the patients. Compliance with continuous positive airway pressure therapy was assessed by average hours of continuous positive airway pressure therapy usage per night. Patients with good compliance (patients using continuous positive airway pressure therapy ≥4h/night) were compared to those with poor compliance (patients using <4h/night). 138 patients were analyzed: 77 (55.8%) were considered compliant while 61 (44.2%) were non-compliant. The comparison between the two groups showed that regular monitoring by a specialist considerably improved compliance with continuous positive airway pressure therapy (odds ratio, OR=2.62). Compliance with continuous positive airway pressure therapy is related to educational components, which can be enhanced with continuous and individualized care to patients with obstructive sleep apnea syndrome. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Electrophysiological response of chicken's jejunal epithelium to increasing levels of T-2 toxin.

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Yunus, Agha Waqar; Kröger, Susan; Tichy, Alexander; Zentek, Jürgen; Böhm, Josef

2013-02-01

The present investigations were conducted to test the effects of T-2 toxin on electrophysiological variables of jejunal epithelium of chicken. Jejunal segments of broilers were monitored in Ussing chambers in the presence of T-2 toxin at the levels of 0 (negative control), 0 (methanol/vehicle control), 0.1, 1, 5, and 10 μg/ml of buffer. T-2 toxin did not affect basal values of short circuit current (I(sc)), transmural potential difference, or tissue conductivity in the jejunal epithelium. T-2 toxin also did not statistically affect glucose-induced electrophysiological variables during the first 3 min of glucose induction. Compared to the vehicle control, the ouabain-sensitive I(sc) was negatively affected (P = 0.008) only under 5 μg of T-2 toxin/ml. Increasing levels of T-2 toxin negatively affected the ouabain-sensitive I(sc) in a cubic (P = 0.007) fashion. These data indicate that acute exposure to moderate levels of T-2 toxin may progressively impair the cation gradient across the jejunal epithelium.

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing.

Science.gov (United States)

Radovich, Milan; Clare, Susan E; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A; Solzak, Jeffrey P; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V; Rufenbarger, Connie; Lillemoe, Heather A; Blosser, Rachel J; Choi, Mi Ran; Sauder, Candice A; Doxey, Diane; Henry, Jill E; Hilligoss, Eric E; Sakarya, Onur; Hyland, Fiona C; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W; Schneider, Bryan P

2014-01-01

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.

Embryo-epithelium interactions during implantation at a glance.

Science.gov (United States)

Aplin, John D; Ruane, Peter T

2017-01-01

At implantation, with the acquisition of a receptive phenotype in the uterine epithelium, an initial tenuous attachment of embryonic trophectoderm initiates reorganisation of epithelial polarity to enable stable embryo attachment and the differentiation of invasive trophoblasts. In this Cell Science at a Glance article, we describe cellular and molecular events during the epithelial phase of implantation in rodent, drawing on morphological studies both in vivo and in vitro, and genetic models. Evidence is emerging for a repertoire of transcription factors downstream of the master steroidal regulators estrogen and progesterone that coordinate alterations in epithelial polarity, delivery of signals to the stroma and epithelial cell death or displacement. We discuss what is known of the cell interactions that occur during implantation, before considering specific adhesion molecules. We compare the rodent data with our much more limited knowledge of the human system, where direct mechanistic evidence is hard to obtain. In the accompanying poster, we represent the embryo-epithelium interactions in humans and laboratory rodents, highlighting similarities and differences, as well as depict some of the key cell biological events that enable interstitial implantation to occur. © 2017. Published by The Company of Biologists Ltd.

A comparison of digital tomosynthesis and chest radiography in evaluating airway lesions using computed tomography as a reference.

Science.gov (United States)

Choo, Ji Yung; Lee, Ki Yeol; Yu, Ami; Kim, Je-Hyeong; Lee, Seung Heon; Choi, Jung Won; Kang, Eun-Young; Oh, Yu Whan

2016-09-01

To compare the diagnostic performance of digital tomosynthesis (DTS) and chest radiography for detecting airway abnormalities, using computed tomography (CT) as a reference. We evaluated 161 data sets from 149 patients (91 with and 70 without airway abnormalities) who had undergone radiography, DTS, and CT to detect airway problems. Radiographs and DTS were evaluated to localize and score the severity of the airway abnormalities, and to score the image quality using CT as a reference. Receiver operating characteristics (ROC), McNemar's test, weighted kappa, and the paired t-test were used for statistical analysis. The sensitivity of DTS was higher (reader 1, 93.51 %; reader 2, 94.29 %) than chest radiography (68.83 %; 71.43 %) in detecting airway lesions. The diagnostic accuracy of DTS (90.91 %; 94.70 %) was also significantly better than that of radiography (78.03 %; 82.58 %, all p chest radiography (1.83, 2.74; p < 0.05) in the results of both readers. The inter-observer agreement with respect to DTS findings was moderate and superior when compared to radiography findings. DTS is a more accurate and sensitive modality than radiography for detecting airway lesions that are easily obscured by soft tissue structures in the mediastinum. • Digital tomosynthesis offers new diagnostic options for airway lesions. • Digital tomosynthesis is more sensitive and accurate than radiography for airway lesions. • Digital tomosynthesis shows better image quality than radiography. • Assessment of lesion severity, via tomosynthesis is comparable to computed tomography.

Comparison Of The I-Gel Supraglottic And King Laryngotracheal Airways In A Simulated Tactical Environment.

Science.gov (United States)

March, Juan A; Tassey, Theresa E; Resurreccion, Noel B; Portela, Roberto C; Taylor, Stephen E

2018-01-01

When working in a tactical environment there are several different airway management options that exist. One published manuscript suggests that when compared to endotracheal intubation, the King LT laryngotracheal airway (KA) device minimizes time to successful tube placement and minimizes exposure in a tactical environment. However, comparison of two different blind insertion supraglottic airway devices in a tactical environment has not been performed. This study compared the I-Gel airway (IGA) to the KA in a simulated tactical environment, to determine if one device is superior in minimizing exposure and minimizing time to successful tube placement. This prospective randomized cross over trial was performed using the same methods and tactical environment employed in a previously published study, which compared endotracheal intubation versus the KA in a tactical environment. The tactical environment was simulated with a one-foot vertical barrier. The participants were paramedic students who wore an Advanced Combat Helmet (ACH) and a ballistic vest (IIIA) during the study. Participants were then randomized to perform tactical airway management on an airway manikin with either the KA or the IGA, and then again using the alternate device. The participants performed a low military type crawl and remained in this low position during each tube placement. We evaluated the time to successful tube placement between the IGA and KA. During attempts, participants were videotaped to monitor their height exposure above the barrier. Following completion, participants were asked which airway device they preferred. Data was analyzed using Student's t-test across the groups for time to ventilation and height of exposure. In total 19 paramedic students who were already at the basic EMT level participated. Time to successful placement for the KA was 39.7 seconds (95%CI: 32.7-46.7) versus 14.4 seconds (95%CI: 12.0-16.9) for the IGA, p tactical environment placement of the IGA for

The ureteric bud epithelium: morphogenesis and roles in metanephric kidney patterning.

Science.gov (United States)

Nagalakshmi, Vidya K; Yu, Jing

2015-03-01

The mammalian metanephric kidney is composed of two epithelial components, the collecting duct system and the nephron epithelium, that differentiate from two different tissues -the ureteric bud epithelium and the nephron progenitors, respectively-of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis, whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return, the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is physiologically divided along the corticomedullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here, we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortico-medullary patterning of the metanephric kidney. © 2015 Wiley Periodicals, Inc.

Airway inflammation in patients affected by obstructive sleep apnea syndrome.

Science.gov (United States)

Salerno, F G; Carpagnano, E; Guido, P; Bonsignore, M R; Roberti, A; Aliani, M; Vignola, A M; Spanevello, A

2004-01-01

Obstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper airway inflammation. The object of the present study was to establish the presence of bronchial inflammation in OSAS subjects. In 16 subjects affected by OSAS, and in 14 healthy volunteers, airway inflammation was detected by the cellular analysis of the induced sputum. OSAS patients, as compared to control subjects, showed a higher percentage of neutrophils (66.7+/-18.9 vs. 25.8+/-15.6) (Pbronchial inflammation characterized by a significant increase in neutrophils.

Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

Science.gov (United States)

Oesterle, Elizabeth C.

2012-01-01

Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

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Lifescience Database Archive (English)

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Intestinal epithelium in inflammatory bowel disease

Directory of Open Access Journals (Sweden)

Mehmet eCoskun

2014-08-01

Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

ProSeal laryngeal mask airway as an alternative to standard endotracheal tube in securing upper airway in the patients undergoing beating-heart coronary artery bypass grafting

Directory of Open Access Journals (Sweden)

Kalpana Shah

2017-01-01

Full Text Available Background: ProSeal laryngeal mask airways (PLMAs are routinely used after failed tracheal intubation as airway rescue, facilitating tracheal intubation by acting as a conduit and to secure airway during emergencies. In long duration surgeries, use of endotracheal tube (ETT is associated with various hemodynamic complications, which are minimally affected during PLMA use. However, except for few studies, there are no significant data available that promote the use of laryngeal mask during cardiac surgery. This prospective study was conducted with the objective of demonstrating the advantages of PLMA over ETT in the patients undergoing beating-heart coronary artery bypass graft (CABG. Methodology: This prospective, interventional study was carried out in 200 patients who underwent beating-heart CABG. Patients were randomized in equal numbers to either ETT group or PLMA group, and various hemodynamic and respiratory parameters were observed at different time points. Results: Patients in PLMA group had mean systolic blood pressure 126.10 ± 5.31 mmHg compared to the patients of ETT group 143.75 ± 6.02 mmHg. Pulse rate in the PLMA group was less (74.52 ± 10.79 per min (P < 0.05 compared to ETT group (81.72 ± 9.8. Thus, hemodynamic changes were significantly lower (P < 0.05 in PLMA than in ETT group. Respiratory parameters such as oxygen saturation, pressure CO 2 (pCO 2 , peak airway pressure, and lung compliance were similar to ETT group at all evaluation times. The incidence of adverse events was also lower in PLMA group. Conclusion: In experience hand, PLMA offers advantages over the ETT in airway management in the patients undergoing beating-heart CABG.

Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

DEFF Research Database (Denmark)

Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

2010-01-01

This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

Hypotonicity induced K+ and anion conductive pathways activation in eel intestinal epithelium

DEFF Research Database (Denmark)

Lionetto, M G; Giordano, M E; De Nuccio, F

2005-01-01

, the activation of 'emergency' systems of rapid cell volume regulation is fundamental in their physiology. The aim of the present work was to study the physiological response to hypotonic stress in a salt-transporting epithelium, the intestine of the euryhaline teleost Anguilla anguilla. Eel intestinal epithelium......, when symmetrically bathed with Ringer solution, develops a net Cl- current giving rise to a negative transepithelial potential at the basolateral side of the epithelium. The eel intestinal epithelium responded to a hypotonic challenge with a biphasic decrease in the transepithelial voltage (V......(te)) and the short circuit current (I(sc)). This electrophysiological response correlated with a regulatory volume decrease (RVD) response, recorded by morphometrical measurement of the epithelium height. Changes in the transepithelial resistance were also observed following the hypotonicity exposure...

Development of the ovarian follicular epithelium.

Science.gov (United States)

Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

1999-05-25

A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women.

Routine airway surveillance in pediatric tracheostomy patients.

Science.gov (United States)

Gergin, Ozgul; Adil, Eelam; Kawai, Kosuke; Watters, Karen; Moritz, Ethan; Rahbar, Reza

2017-06-01

The aim of this study is to review airway findings in children with tracheostomies who underwent surveillance direct laryngoscopy and bronchoscopy (DLB) to determine the yield of routine airway evaluation in these patients. Retrospective chart review at tertiary referral children's hospital. A retrospective chart review was conducted of all of the children with tracheostomies who underwent DLB after tracheostomy between 1984 and 2015. A total of 303 patients met inclusion criteria. The median time interval between tracheostomy and first follow-up DLB was 12.0 months (IQR 4.8-28.9 months). There was no significant difference in the incidence of airway lesions between patients who underwent endoscopy tracheostomy versus those who had a longer time interval between tracheostomy and DLB (p = 0.16). One hundred sixty seven patients (55.1%) were diagnosed with lesions, with suprastomal granulation (39.9%) being the most common. Symptomatic patients were significantly more likely to have an airway lesion identified (69.9% versus 42.0%; p tracheostomy were significantly more likely to have an airway lesion (p = 0.01). The high incidence of airway lesions noted during surveillance DLB support the utility of routine airway endoscopy in pediatric tracheostomy patients. Symptomatic patients, those with ventilator dependence, or cardiopulmonary or trauma indications for tracheostomy are more likely to have airway lesions and should be monitored closely. The ideal time interval between surveillance endoscopies needs to be examined further. Copyright © 2017. Published by Elsevier B.V.

Effect of Low-Dose, Long-Term Roxithromycin on Airway Inflammation and Remodeling of Stable Noncystic Fibrosis Bronchiectasis

Directory of Open Access Journals (Sweden)

Jifeng Liu

2014-01-01

Full Text Available Background. Noncystic fibrosis bronchiectasis (NCFB is characterized by airway expansion and recurrent acute exacerbations. Macrolide has been shown to exhibit anti-inflammatory effects in some chronic airway diseases. Objective. To assess the efficacy of roxithromycin on airway inflammation and remodeling in patients with NCFB under steady state. Methods. The study involved an open-label design in 52 eligible Chinese patients with NCFB, who were assigned to control (receiving no treatment and roxithromycin (receiving 150 mg/day for 6 months groups. At baseline and 6 months, the inflammatory markers such as interleukin- (IL-8, neutrophil elastase (NE, matrix metalloproteinase- (MMP9, hyaluronidase (HA, and type IV collagen in sputum were measured, along with the detection of dilated bronchus by throat computed tomography scan, and assessed the exacerbation. Results. Forty-three patients completed the study. The neutrophil in the sputum was decreased in roxithromycin group compared with control (P<0.05. IL-8, NE, MMP-9, HA, and type IV collagen in sputum were also decreased in roxithromycin group compared with the control group (all P<0.01. Airway thickness of dilated bronchus and exacerbation were reduced in roxithromycin group compared with the control (all P<0.05. Conclusions. Roxithromycin can reduce airway inflammation and airway thickness of dilated bronchus in patients with NCFB.