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Sample records for central airway function

  1. Functional phenotype of airway myocytes from asthmatic airways

    NARCIS (Netherlands)

    Wright, David B.; Trian, Thomas; Siddiqui, Sana; Pascoe, Chris D.; Ojo, Oluwaseun O.; Johnson, Jill R.; Dekkers, Bart G. J.; Dakshinamurti, Shyamala; Bagchi, Rushita; Burgess, Janette K.; Kanabar, Varsha

    2013-01-01

    In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a 'healthy' ASM cell become 'asthmatic' still remai

  2. Central airways remodeling in COPD patients

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    Pini L

    2014-09-01

    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects

  3. Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function

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    Bunn Janice Y

    2010-03-01

    Full Text Available Abstract Background Asthma is a chronic inflammatory disease of the airway that is characterized by a Th2-type of immune response with increasing evidence for involvement of Th17 cells. The role of IL-6 in promoting effector T cell subsets suggest that IL-6 may play a functional role in asthma. Classically IL-6 has been viewed as an inflammatory marker, along with TNFα and IL-1β, rather than as regulatory cytokine. Objective To investigate the potential relationship between IL-6 and other proinflammatory cytokines, Th2/Th17 cytokines and lung function in allergic asthma, and thus evaluate the potential role of IL-6 in this disease. Methods Cytokine levels in induced sputum and lung function were measured in 16 healthy control and 18 mild-moderate allergic asthmatic subjects. Results The levels of the proinflammatory biomarkers TNFα and IL-1β were not different between the control and asthmatic group. In contrast, IL-6 levels were specifically elevated in asthmatic subjects compared with healthy controls (p S = 0.53, p Conclusions In mild-moderate asthma, IL-6 dissociates from other proinflammatory biomarkers, but correlates with IL-13 levels. Furthermore, IL-6 may contribute to impaired lung function in allergic asthma.

  4. Therapeutic Bronchoscopy for Malignant Central Airway Obstruction

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    Ernst, Armin; Grosu, Horiana B.; Lei, Xiudong; Diaz-Mendoza, Javier; Slade, Mark; Gildea, Thomas R.; Machuzak, Michael S.; Jimenez, Carlos A.; Toth, Jennifer; Kovitz, Kevin L.; Ray, Cynthia; Greenhill, Sara; Casal, Roberto F.; Almeida, Francisco A.; Wahidi, Momen M.; Eapen, George A.; Feller-Kopman, David; Morice, Rodolfo C.; Benzaquen, Sadia; Tremblay, Alain; Simoff, Michael; Kovitz, Kevin; Greenhill, Sara; Gildea, Thomas R.; Machuzak, Michael; Almeida, Francisco A.; Cicenia, Joseph; Wahidi, Momen; Mahmood, Kamran; MacEachern, Paul; Tremblay, Alain; Simoff, Michael; Diaz-Mendoza, Javier; Ray, Cynthia; Feller-Kopman, David; Yarmus, Lonny; Estrada-Y-Martin, Rosa; Casal, Roberto F.; Toth, Jennifer; Karunakara, Raj; Slade, Mark; Ernst, Armin; Rafeq, Samaan; Ost, David; Eapen, George A.; Jimenez, Carlos A.; Morice, Rodolfo C.; Benzaquen, Sadia; Puchalski, Jonathan

    2015-01-01

    BACKGROUND: There is significant variation between physicians in terms of how they perform therapeutic bronchoscopy, but there are few data on whether these differences impact effectiveness. METHODS: This was a multicenter registry study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was technical success, defined as reopening the airway lumen to > 50% of normal. Secondary outcomes were dyspnea as measured by the Borg score and health-related quality of life (HRQOL) as measured by the SF-6D. RESULTS: Fifteen centers performed 1,115 procedures on 947 patients. Technical success was achieved in 93% of procedures. Center success rates ranged from 90% to 98% (P = .02). Endobronchial obstruction and stent placement were associated with success, whereas American Society of Anesthesiology (ASA) score > 3, renal failure, primary lung cancer, left mainstem disease, and tracheoesophageal fistula were associated with failure. Clinically significant improvements in dyspnea occurred in 90 of 187 patients measured (48%). Greater baseline dyspnea was associated with greater improvements in dyspnea, whereas smoking, having multiple cancers, and lobar obstruction were associated with smaller improvements. Clinically significant improvements in HRQOL occurred in 76 of 183 patients measured (42%). Greater baseline dyspnea was associated with greater improvements in HRQOL, and lobar obstruction was associated with smaller improvements. CONCLUSIONS: Technical success rates were high overall, with the highest success rates associated with stent placement and endobronchial obstruction. Therapeutic bronchoscopy should not be withheld from patients based solely on an assessment of risk, since patients with the most dyspnea and lowest functional status benefitted the most. PMID:25358019

  5. CT quantification of central airway in tracheobronchomalacia

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    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.

  6. Modeling the Nonlinear Motion of the Rat Central Airways.

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    Ibrahim, G; Rona, A; Hainsworth, S V

    2016-01-01

    Advances in volumetric medical imaging techniques allowed the subject-specific modeling of the bronchial flow through the first few generations of the central airways using computational fluid dynamics (CFD). However, a reliable CFD prediction of the bronchial flow requires modeling of the inhomogeneous deformation of the central airways during breathing. This paper addresses this issue by introducing two models of the central airways motion. The first model utilizes a node-to-node mapping between the discretized geometries of the central airways generated from a number of successive computed tomography (CT) images acquired dynamically (without breath hold) over the breathing cycle of two Sprague-Dawley rats. The second model uses a node-to-node mapping between only two discretized airway geometries generated from the CT images acquired at end-exhale and at end-inhale along with the ventilator measurement of the lung volume change. The advantage of this second model is that it uses just one pair of CT images, which more readily complies with the radiation dosage restrictions for humans. Three-dimensional computer aided design geometries of the central airways generated from the dynamic-CT images were used as benchmarks to validate the output from the two models at sampled time-points over the breathing cycle. The central airway geometries deformed by the first model showed good agreement to the benchmark geometries within a tolerance of 4%. The central airway geometry deformed by the second model better approximated the benchmark geometries than previous approaches that used a linear or harmonic motion model.

  7. [Use of airway stent subsequent to endoscopic Nd-YAG laser treatment in central airway obstruction].

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    Akaogi, E; Yuasa, H; Ishibashi, O; Inage, Y; Dai, Y; Sato, Y; Ishikawa, S; Morita, R; Onizuka, M; Mitsui, K

    1992-01-01

    Ten cases of central airway obstruction mainly caused by extrinsic compression due to the growth of extratracheal malignant tumors or longitudinal extension of tracheal adenoid cystic carcinomas, underwent palliative intubation subsequent to endoscopic Nd-YAG laser treatment. Mean length of the severe stenosis in these cases was 4.4 cm (3-7 cm). Sole application of endoscopic Nd-YAG laser to the stenosis failed relief of the symptom and an immediate palliative intubation was recommended. Mean time of the temporary intubation was 7 days (4-11 days). Airway was maintained by this intubation and also retained enough after extubation. Therefore, it seemed that, in a palliative treatment of the central airway severe stenosis, usefulness of the combination management of Nd-YAG laser with following temporary intubation was revealed. However, in order to maintain the airway for recurrence of the obstruction, use of indwelling airway stents seemed a better application. The longest period of follow-up in the cases treated by indwelling airway stents was 6 months and one of the cases is a now in comfortable state.

  8. The airway epithelium is central to the pathogenesis of asthma.

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    Holgate, Stephen T

    2008-03-01

    Asthma is an inflammatory disorder principally involving the conducting airways and characterised by infiltration of the airway wall with a range of inflammatory cells driven in large part by activation of Th2-type lymphocytes, mast cells and eosinophils. However a key component of asthma is the structural change that involves all of the elements of the airway wall. Here evidence is presented to suggest that the airway epithelium in asthma is fundamentally abnormal with increased susceptibility to environmental injury and impaired repair associated with activation of the epithelial-mesenchymal trophic unit (EMTU). In addition to adopting an activated phenotype, the barrier function of the epithelium is impaired through defective tight junction formation thereby facilitating penetration of potentially toxic or damaging environmental insults. Activated and repairing epithelial cells generate a range of growth factors that are involved in the early life origins of this disease as well as its progression in the form of mucous metaplasia and airway wall remodeling. By placing the epithelium at the forefront of asthma pathogenesis, different approaches to treatment can be devised focused more on protecting vulnerable airways against environmental injury rather than focusing on suppressing airway inflammation or manipulating the immune response.

  9. Central airways stenoses management--a single institution experience.

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    Pereszlenyi, A; Majer, I; Janik, M; Demian, J; Igaz, M; Knappkova, S; Eftimova, P; Benej, R; Harustiak, S

    2004-01-01

    Tracheal stenosis is a serious, life-threatening disease with an increasing tendency. The number of complicated tracheal lesions, where resection and anastomosis can not be performed, still increases and the situation requires solution by endoprosthesis. Consequent the management of such complicated obstructive tracheal lesions is individual and time-consuming. The main objective of this study is to review the single institution experience with central airways stenosis treatment and to define the role of endotracheal stenting in tracheal reconstruction surgery. This study presents the retrospective analysis of tracheal stenosis reconstruction by means of our own modification of Montgomery T-tube. (Tab. 3, Fig. 3, Ref. 12.)

  10. Inhaled corticosteroids and growth of airway function in asthmatic children

    NARCIS (Netherlands)

    Merkus, PJFM; van Pelt, W; van Houwelingen, JC; van Essen-Zandvliet, LEM; Duiverman, EJ; Kerrebijn, KF; Quanjer, PH

    2004-01-01

    Airway inflammation and remodelling play an important role in the pathophysiology of asthma. Remodelling may affect childhood lung function, and this process may be reversed by anti-inflammatory treatment. The current study assessed longitudinaily whether asthma affects growth of airway function rel

  11. Complications Following Therapeutic Bronchoscopy for Malignant Central Airway Obstruction

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    Ernst, Armin; Grosu, Horiana B.; Lei, Xiudong; Diaz-Mendoza, Javier; Slade, Mark; Gildea, Thomas R.; Machuzak, Michael; Jimenez, Carlos A.; Toth, Jennifer; Kovitz, Kevin L.; Ray, Cynthia; Greenhill, Sara; Casal, Roberto F.; Almeida, Francisco A.; Wahidi, Momen; Eapen, George A.; Yarmus, Lonny B.; Morice, Rodolfo C.; Benzaquen, Sadia; Tremblay, Alain; Simoff, Michael; Kovitz, Kevin L.; Greenhill, Sara; Gildea, Thomas R.; Machuzak, Michael; Almeida, Francisco A.; Cicenia, Joseph; Wahidi, Momen; Mahmood, Kamran; MacEachern, Paul; Tremblay, Alain; Simoff, Michael; Diaz-Mendoza, Javier; Ray, Cynthia; Feller-Kopman, David; Yarmus, Lonny B.; Estrada-Y-Martin, Rosa; Casal, Roberto F.; Toth, Jennifer; Karunakara, Raj; Slade, Mark; Ernst, Armin; Rafeq, Samaan; Ost, David E.; Eapen, George A.; Jimenez, Carlos A.; Morice, Rodolfo C.; Benzaquen, Sadia; Puchalski, Jonathan

    2015-01-01

    BACKGROUND: There are significant variations in how therapeutic bronchoscopy for malignant airway obstruction is performed. Relatively few studies have compared how these approaches affect the incidence of complications. METHODS: We used the American College of Chest Physicians (CHEST) Quality Improvement Registry, Evaluation, and Education (AQuIRE) program registry to conduct a multicenter study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was the incidence of complications. Secondary outcomes were incidence of bleeding, hypoxemia, respiratory failure, adverse events, escalation in level of care, and 30-day mortality. RESULTS: Fifteen centers performed 1,115 procedures on 947 patients. There were significant differences among centers in the type of anesthesia (moderate vs deep or general anesthesia, P 3, redo therapeutic bronchoscopy, and moderate sedation. The 30-day mortality was 14.8%; mortality varied among centers (range, 7.7%-20.2%, P = .02). Risk factors for 30-day mortality included Zubrod score > 1, ASA score > 3, intrinsic or mixed obstruction, and stent placement. CONCLUSIONS: Use of moderate sedation and stents varies significantly among centers. These factors are associated with increased complications and 30-day mortality, respectively. PMID:25741903

  12. Distinct PKA and Epac compartmentalization in airway function and plasticity

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Racke, Kurt; Schmidt, Martina

    2013-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases characterized by airway obstruction, airway inflammation and airway remodelling. Next to inflammatory cells and airway epithelial cells, airway mesenchymal cells, including airway smooth muscle cells and (myo)fibro

  13. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells

    NARCIS (Netherlands)

    Hoffmann, Roland F.; Zarrintan, Sina; Brandenburg, Simone M.; Kol, Arjan; de Bruin, Harold G.; Jafari, Shabnam; Dijk, Freark; Kalicharan, Dharamdajal; Kelders, Marco; Gosker, Harry R.; ten Hacken, Nick H. T.; van der Want, Johannes J.; van Oosterhout, Antoon J. M.; Heijink, Irene H.

    2013-01-01

    Background: Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation. We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis. Methods:

  14. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells

    NARCIS (Netherlands)

    Hoffmann, Roland F; Zarrintan, Sina; Brandenburg, Simone M; Kol, Arjan; de Bruin, Harold G; Jafari, Shabnam; Dijk, Freark; Kalicharan, Dharamdajal; Kelders, Marco; Gosker, Harry R; Ten Hacken, Nick Ht; van der Want, Johannes J; van Oosterhout, Antoon Jm; Heijink, Irene H

    2013-01-01

    BACKGROUND: Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation. We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis. METHODS:

  15. Methylene Blue-Aided In Vivo Staining of Central Airways during Flexible Bronchoscopy

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    Sabine Zirlik

    2012-01-01

    Full Text Available Background. The early diagnosis of malignant and premalignant changes of the bronchial mucosa remains a major challenge during bronchoscopy. Intravital staining techniques are not new. Previous small case series suggested that analysis of the bronchial mucosal surface using chromoendoscopy allows a prediction between neoplastic and nonneoplastic lesions. Objectives. The aim of the present study was to evaluate chromobronchoscopy as a method to identify malignant and premalignant lesions in the central airways in a prospective manner. Methods. In 26 patients we performed chromoendoscopy with 0.1% methylene blue during ongoing flexible white light bronchoscopy. Circumscribed lesions in central airways were further analyzed by biopsies and histopathologic examination. Results. In the majority of cases neither flat nor polypoid lesions in the central airways were stained by methylene blue. In particular, exophytic growth of lung cancer did not show any specific pattern in chromobronchoscopy. However, a specific dye staining was detected in one case where exophytic growth of metastatic colorectal cancer was present in the right upper lobe. In two other cases, a circumscribed staining was noted in unsuspicious mucosa. But histology revealed inflammation only. Conclusions. In contrast to previous studies, the present findings clearly indicate that chromobronchoscopy is not useful for early detection of malignant or premalignant lesions of the central airways.

  16. Organophosphorus pesticides decrease M2 muscarinic receptor function in guinea pig airway nerves via indirect mechanisms.

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    Becky J Proskocil

    Full Text Available BACKGROUND: Epidemiological studies link organophosphorus pesticide (OP exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon and parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced airway hyperreactivity involves M2 muscarinic receptor dysfunction on airway nerves independent of acetylcholinesterase (AChE inhibition, but how OPs inhibit neuronal M2 receptors in airways is not known. In the central nervous system, OPs interact directly with neurons to alter muscarinic receptor function or expression; therefore, in this study we tested whether the OP parathion or its oxon metabolite, paraoxon, might decrease M2 receptor function on peripheral neurons via similar direct mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Intravenous administration of paraoxon, but not parathion, caused acute frequency-dependent potentiation of vagally-induced bronchoconstriction and increased electrical field stimulation (EFS-induced contractions in isolated trachea independent of AChE inhibition. However, paraoxon had no effect on vagally-induced bradycardia in intact guinea pigs or EFS-induced contractions in isolated ileum, suggesting mechanisms other than pharmacologic antagonism of M2 receptors. Paraoxon did not alter M2 receptor expression in cultured cells at the mRNA or protein level as determined by quantitative RT-PCR and radio-ligand binding assays, respectively. Additionally, a biotin-labeled fluorophosphonate, which was used as a probe to identify molecular targets phosphorylated by OPs, did not phosphorylate proteins in guinea pig cardiac membranes that were recognized by M2 receptor antibodies. CONCLUSIONS/SIGNIFICANCE: These data indicate that neither direct pharmacologic antagonism nor downregulated expression of M2 receptors contributes to OP inhibition of M2 function in airway nerves, adding to the growing evidence of non-cholinergic mechanisms of OP neurotoxicity.

  17. Determination of optimal parameters for three-dimensional reconstruction images of central airways using helical CT

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    Hirose, Takahumi; Akata, Soichi; Matsuno, Naoto; Nagao, Takeshi; Abe, Kimihiko [Tokyo Medical Coll. (Japan)

    2002-01-01

    Three-dimensional (3D) image reconstruction of central airways using helical CT requires several user-defined parameters that exceed the requirements of conventional CT. The purpose of this study was to evaluate the optimal parameters for 3D images of central airways using helical CT. In our experimental study using a piglet immediately after sacrifice, 3D images of the central airway were evaluated with changes of 3D imaging parameters, such as detector collimation (1, 2, 3 and 6 mm), table speed (1, 2, 3 and 5 mm/sec), tube electric current (50, 100, 150, 200 and 250 mA), reconstruction interval (0.3, 0.5, 1, 2 and 3 mm), algorithm (mediastinum and lung) and interpolation method (180 deg and 360 deg). To minimize detector collimation, table speed, and reconstruction interval could provide the best 3D images of the central airway. Stair-step artifacts could also be reduced with a slow table speed. However, decreasing the collimation and table speed decreases not only the effective section thickness but also the scan coverage that can be achieved with a helical CT. For routine diagnosis, we conclude that optimal parameters for 3D images of the central airway are to minimize the table speed necessary to cover the volume of interest and to set detector collimation to 1/2 of the table speed. The reconstruction intervals should also be selected at up to 1/2 of the detector collimation, but with trade-offs of increased image processing time, data storage requirements, and physician time for image review. Regarding to tube electric current, 200 mA or more was necessary. Pixel noise increased with the algorithm for the lung. The 180 deg interpolation is better than 360 deg interpolation due to thin effective section thickness. (author)

  18. Successful Flexible Bronchoscopic Management of Dynamic Central Airway Obstruction by a Large Tracheal Carcinoid Tumor

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    Vijay Hadda

    2014-01-01

    Full Text Available Typical carcinoid of the trachea presenting as an endoluminal polypoidal mass is a rare occurrence. Herein, we report a case of a 34-year-old female patient who presented with features of central airway obstruction. Flexible bronchoscopy demonstrated a large pedunculated growth arising from the lower end of the trachea near carina which was flopping in and out of the main tracheal lumen and the proximal right bronchus leading to dynamic airway obstruction. Successful electrosurgical excision (using a snare loop of the polypoidal growth was performed using the flexible bronchoscope itself. The patient had immediate relief of airway obstruction and histopathological examination of the polyp demonstrated features of typical carcinoid (WHO Grade I neuroendocrine tumor.

  19. Association between peripheral airway function and neutrophilic inflammation in asthma

    NARCIS (Netherlands)

    Farah, Claude S.; Keulers, Laurien A. B.; Hardaker, Kate M.; Peters, Matthew J.; Berend, Norbert; Postma, Dirkje S.; Salome, Cheryl M.; King, Gregory G.

    2015-01-01

    Background and objectiveSmall airway dysfunction is associated with asthma severity and control, but its association with airway inflammation is unknown. The aim was to determine the association between sputum inflammatory cells and the site of small airway dysfunction, measured by multiple breath n

  20. Determinants of lung function and airway hyperresponsiveness in asthmatic children

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S; Anhøj, J;

    2007-01-01

    Genetic Study (SAGA). RESULTS: The primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N=919). FEV(1) percent predicted (FEV(1)% pred) was 0......BACKGROUND: Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying...... effect of steroid treatment. METHODS: We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma...

  1. Cryorecanalization after cryosurgery for immediate treatment on central airway obstruction via flexible bronchoscope

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    Yongqun Li; Huasong Feng; Zhoushan Nie; Jiguang Meng; Xinmin Ding; Zhihai Han

    2012-01-01

    Objective: In order to achieve immediate relief of central airway obstruction caused by malignant tumor after interventional therapy, we observed the efficacy and safety of cryorecanalization after cryosurgery via flexible bronchoscope. Methods: A total of 64 cases of patients in all suffered from central airway obstruction were observed and treated by applying cryorecanalization after cryosurgery via flexible bronchoscope. Divide the operation into two steps, including cryosurgery and cryorecanalization. Evaluate the therapeutic effect immediately after the treatment, wherein the evaluating indicator includes preoperative and postoperative dyspnea indexes, quality of life score, bronchoscopy, etc. The surgical safety assessment is mainly by observing the risk of bleeding in the surgery. Results: Forty cases (62.5%) has postoperative dyspnea score improved at least one level compared with preoperative dyspnea score, 24 patients (37.5%) have no significant improvement on dyspnea score. Quality of life score (Karnofsky score): preoperative 52 ± 18.7 points, postoperative 70 ± 9.2 points. Bronchoscopy review: complete success in 12 cases (18.8%), partial success in 45 cases (70.3%), no success in 7 cases (12%).89.1% overall clinical efficiency was achieved. In the surgery, the control to bleeding was satisfactory since no severe bleeding, moderate bleeding in 14 cases (21.9%) and mild bleeding in 50 cases (78.1%) were found as well as rigid bronchoscope was free. Conclusion: The central airway obstruction can be immediately relieved by cryorecanalization after cryosurgery via flexible bronchoscope with satisfactory effects and higher surgical safety.

  2. Viral bronchiolitis in young rats causes small airway lesions that correlate with reduced lung function.

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    Sorkness, Ronald L; Szakaly, Renee J; Rosenthal, Louis A; Sullivan, Ruth; Gern, James E; Lemanske, Robert F; Sun, Xin

    2013-11-01

    Viral illness with wheezing during infancy is associated with the inception of childhood asthma. Small airway dysfunction is a component of childhood asthma, but little is known about how viral illness at an early age may affect the structure and function of small airways. We used a well-characterized rat model of postbronchiolitis chronic airway dysfunction to address how postinfectious small airway lesions affect airway physiological function and if the structure/function correlates persist into maturity. Brown Norway rats were sham- or virus inoculated at 3 to 4 weeks of age and allowed to recover from the acute illness. At 3 to 14 months of age, physiology (respiratory system resistance, Newtonian resistance, tissue damping, and static lung volumes) was assessed in anesthetized, intubated rats. Serial lung sections revealed lesions in the terminal bronchioles that reduced luminal area and interrupted further branching, affecting 26% (range, 13-39%) of the small airways at 3 months of age and 22% (range, 6-40%) at 12 to 14 months of age. At 3 months of age (n = 29 virus; n = 7 sham), small airway lesions correlated with tissue damping (rs = 0.69) but not with Newtonian resistance (rs = 0.23), and Newtonian resistance was not elevated compared with control rats, indicating that distal airways were primarily responsible for the airflow obstruction. Older rats (n = 7 virus; n = 6 sham) had persistent small airway dysfunction and significantly increased Newtonian resistance in the postbronchiolitis group. We conclude that viral airway injury at an early age may induce small airway lesions that are associated quantitatively with small airway physiological dysfunction early on and that these defects persist into maturity.

  3. A mechanical design principle for tissue structure and function in the airway tree.

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    LaPrad, Adam S; Lutchen, Kenneth R; Suki, Béla

    2013-01-01

    With every breath, the dynamically changing mechanical pressures must work in unison with the cells and soft tissue structures of the lung to permit air to efficiently traverse the airway tree and undergo gas exchange in the alveoli. The influence of mechanics on cell and tissue function is becoming apparent, raising the question: how does the airway tree co-exist within its mechanical environment to maintain normal cell function throughout its branching structure of diminishing dimensions? We introduce a new mechanical design principle for the conducting airway tree in which mechanotransduction at the level of cells is driven to orchestrate airway wall structural changes that can best maintain a preferred mechanical microenvironment. To support this principle, we report in vitro radius-transmural pressure relations for a range of airway radii obtained from healthy bovine lungs and model the data using a strain energy function together with a thick-walled cylinder description. From this framework, we estimate circumferential stresses and incremental Young's moduli throughout the airway tree. Our results indicate that the conducting airways consistently operate within a preferred mechanical homeostatic state, termed mechanical homeostasis, that is characterized by a narrow range of circumferential stresses and Young's moduli. This mechanical homeostatic state is maintained for all airways throughout the tree via airway wall dimensional and mechanical relationships. As a consequence, cells within the airway walls throughout the airway tree experience similar oscillatory strains during breathing that are much smaller than previously thought. Finally, we discuss the potential implications of how the maintenance of mechanical homeostasis, while facilitating healthy tissue-level alterations necessary for maturation, may lead to airway wall structural changes capable of chronic asthma.

  4. LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION

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    Chen, Kun; Hoffman, Eric A.; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

    2017-01-01

    The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the “normal” subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors.

  5. Airway hyperresponsiveness and development of lung function in adolescence and adulthood

    DEFF Research Database (Denmark)

    Harmsen, Lotte; Ulrik, Charlotte Suppli; Porsbjerg, Celeste;

    2014-01-01

    Long-term longitudinal studies of lung function from childhood to adulthood are important in linking our understanding of childhood risk factors to adult disease. Airway hyperresponsiveness has been shown to independently affect lung function growth in studies of adolescence. The objective...... of the study was to test the hypothesis that airway hyperresponsiveness has an independent deleterious effect on lung function in adolescence that extends into adulthood....

  6. Effects of lung inflation on airway heterogeneity during histaminergic bronchoconstriction.

    Science.gov (United States)

    Kaczka, David W; Mitzner, Wayne; Brown, Robert H

    2013-09-01

    Lung inflation has been shown to dilate airways by altering the mechanical equilibrium between opposing airway and parenchymal forces. However, it is not known how heterogeneously such dilation occurs throughout the airway tree. In six anesthetized dogs, we measured the diameters of five to six central airway segments using high-resolution computed tomography, along with respiratory input impedance (Zrs) during generalized aerosol histamine challenge, and local histamine challenge in which the agonist was instilled directly onto the epithelia of the imaged central airways. Airway diameters and Zrs were measured at 12 and 25 cmH2O. The Zrs spectra were fitted with a model that incorporated continuous distributions of airway resistances. Airway heterogeneity was quantified using the coefficient of variation for predefined airway distribution functions. Significant reductions in average central airway diameter were observed at 12 cmH2O for both aerosolized and local challenges, along with significant increases upon inflation to 25 cmH2O. No significant differences were observed for the coefficient of variation of airway diameters under any condition. Significant increases in effective airway resistance as measured by Zrs were observed only for the aerosolized challenge at 12 cmH2O, which was completely reversed upon inflation. We conclude that the lung periphery may be the most dominant contributor to increases in airway resistance and tissue elastance during bronchoconstriction induced by aerosolized histamine. However, isolated constriction of only a few central airway segments may also affect tissue stiffness via interdependence with their surrounding parenchyma.

  7. Reconstructive procedures for impaired upper airway function: laryngeal respiration

    Directory of Open Access Journals (Sweden)

    Müller, Andreas

    2005-09-01

    Full Text Available The larynx is the "bottleneck" of the human airway. For this reason, the effects of stenosing laryngeal pathologies on the vital factor respiratory gas exchange are particularly critical. Internal stabilization is a prerequisite for recovery of the laryngeal respiratory function in severe forms of inspiratory collapse (laryngomalacia. Effective laser surgery techniques have been developed to this end in recent years.Glottis-dilating surgery in cases of bilateral vocal cord motion impairment is now moving in the direction of endoscopic laser cordotomy or cordectomy, whereas arytenoidectomy and open surgical procedures are now used only rarely due to higher secondary morbidity rates. In individual cases, in particular if functional recovery is expected, temporary laterofixation of a vocal cord using an endoscopic suturing technique can be a helpful approach.Extensive laryngeal defects can be covered by means of composite grafts with mucosal lining, a supporting skeleton and their own vascularization. Autologous transplantation of the larynx, with its complex surgical and immunological problems, has become a manageable procedure. The problems of post-transplantation reinnervation and risk assessment of immunosuppression-induced recurrence of the tumor are still under consideration. Reanimation of the bilaterally paralyzed larynx by means of neurorrhaphy (neurosuture, neural grafting and, more recently, functional electrostimulation (pacemaker represents a challenge for the coming years. In most cases of paralysis of the recurrent laryngeal nerve, a part of the muscles is maintained by synkinetic reinnervation when therapy is carried out, which however also prevents effective vocal cord movement due to simultaneous activity of agonists and antagonists. Modulation of reinnervation by means of electrostimulation and modern genetic therapy approaches justify hopes of better outcomes in the future.

  8. Small airway function changes and its clinical significance of asthma patients in different clinical phases

    Institute of Scientific and Technical Information of China (English)

    Yan-Hui Zhou; Jun-Ti Lu

    2016-01-01

    Objective:To observe the small airways function changes of asthmatic patients in different clinical phases and to discuss its clinical significance.Methods:A total of 127 patients diagnosed as asthma were selected randomly and pulmonary function (PF) of them was determined by conventional method. Then they were divided into A, B and C group based on PF results. All 34 patients in A group suffered from acute asthma attack for the first time. All 93 patients in B group had been diagnosed as asthma but in remission phase. C Group was regarded as Control group with 20 healthy volunteers. Then FEV1, FEF50%, FEF75% levels of patients in each group were analyzed, and FEV1, FEF75% and FEF50% levels of patients in each group were compared after bronchial dilation test.Results:It was found that most patients in group A and B had abnormal small airways function, and their small airways function was significantly different compared with that of group C (P<0.01). In addition, except for group C, FEF75%, FEF50% levels in A and B group were improved more significantly than FEV1 levels (P<0.01).Conclusions:Asthma patients in acute phase all have abnormal small airways function. Most asthma patients in remission phase also have abnormal small airways function. After bronchial dilation test, whether patients in acute phase or in remission phase, major and small airways function of them are improved, but improvement of small airways function is weaker than that of major airways. This indicates that asthma respiratory tract symptoms in different phases exists all the time and so therapeutic process is needed to perform step by step.

  9. Effect of tiotropium bromide combined with salmeterol fluticasone inhalation on airway function and airway inflammation in patients with moderate-severe stable COPD

    Institute of Scientific and Technical Information of China (English)

    Min Xiang

    2016-01-01

    Objective:To analyze the effect of tiotropium bromide combined with salmeterol fluticasone inhalation on airway function and airway inflammation in patients with moderate-severe stable COPD.Methods: A total of 118 patients with moderate-severe stable COPD were randomly divided into observation group and control group (n=59), control group accepted routine treatment, observation group received tiotropium bromide combined with salmeterol fluticasone inhalation treatment, and then differences in the levels of small airway function and airway wall parameters, the content of inflammatory factors and chemokines in serum and so on were compared between two groups of patients after 2 weeks of treatment.Results:After 2 weeks of treatment, small airway function parameters FEF25, FEF25-75 and FEF75 levels of observation group were significantly higher than those of control group, airway wall parameters WT, WA and T/D levels were significantly lower than those of control group, and AI level was significantly higher than that of control group; MIP-1α, PCT, NF-κB, IL-6, CRP, Eotaxin, CCL18, Lymphotactin, sFKN and MCP-1 content in serum of observation group were significantly lower than those of control group while sTNFR content was significantly higher than that of control group.Conclusions:Tiotropium bromide combined with salmeterol fluticasone inhalation therapy can optimize the overall condition in patients with moderate-severe stable COPD, which is specifically reflected on the control of the airway function and the degree of inflammation.

  10. EMS-physicians' self reported airway management training and expertise; a descriptive study from the Central Region of Denmark

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    Rognås Leif K

    2011-02-01

    Full Text Available Abstract Background Prehospital advanced airway management, including prehospital endotracheal intubation is challenging and recent papers have addressed the need for proper training, skill maintenance and quality control for emergency medical service personnel. The aim of this study was to provide data regarding airway management-training and expertise from the regional physician-staffed emergency medical service (EMS. Methods The EMS in this part of The Central Region of Denmark is a two tiered system. The second tier comprises physician staffed Mobile Emergency Care Units. The medical directors of the programs supplied system data. A questionnaire addressing airway management experience, training and knowledge was sent to the EMS-physicians. Results There are no specific guidelines, standard operating procedures or standardised program for obtaining and maintaining skills regarding prehospital advanced airway management in the schemes covered by this study. 53/67 physicians responded; 98,1% were specialists in anesthesiology, with an average of 17,6 years of experience in anesthesiology, and 7,2 years experience as EMS-physicians. 84,9% reported having attended life support course(s, 64,2% an advanced airway management course. 24,5% fulfilled the curriculum suggested for Danish EMS physicians. 47,2% had encountered a difficult or impossible PHETI, most commonly in a patient in cardiac arrest or a trauma patient. Only 20,8% of the physicians were completely familiar with what back-up devices were available for airway management. Conclusions In this, the first Danish study of prehospital advanced airway management, we found a high degree of experience, education and training among the EMS-physicians, but their equipment awareness was limited. Check-outs, guidelines, standard operating procedures and other quality control measures may be needed.

  11. Diastolic function and functional capacity after a single session of continuous positive airway pressure in patients with compensated heart failure

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    Marjory Fernanda Bussoni

    2014-01-01

    Full Text Available OBJECTIVE: The effects of acute continuous positive airway pressure therapy on left ventricular diastolic function and functional capacity in patients with compensated systolic heart failure remain unclear. METHODS: This randomized, double-blind, placebo-controlled clinical trial included 43 patients with heart failure and a left ventricular ejection fraction <0.50 who were in functional classes I-III according to the New York Heart Association criteria. Twenty-three patients were assigned to continuous positive airway pressure therapy (10 cmH2O, while 20 patients received placebo with null pressure for 30 minutes. All patients underwent a 6-minute walk test (6MWT and Doppler echocardiography before and immediately after intervention. Clinicaltrials.gov: NCT01088854. RESULTS: The groups had similar clinical and echocardiographic baseline variables. Variation in the diastolic function index (e′ after intervention was associated with differences in the distance walked in both groups. However, in the continuous positive airway pressure group, this difference was greater (continuous positive airway pressure group: Δ6MWT = 9.44+16.05×Δe′, p = 0.002; sham group: Δ6MWT = 7.49+5.38×Δe′; p = 0.015. There was a statistically significant interaction between e′ index variation and continuous positive airway pressure for the improvement of functional capacity (p = 0.020. CONCLUSIONS: Continuous positive airway pressure does not acurately change the echocardiographic indexes of left ventricle systolic or diastolic function in patients with compensated systolic heart failure. However, 30-minute continuous positive airway pressure therapy appears to have an effect on left ventricular diastolic function by increasing functional capacity.

  12. Cigarette smoke impairs airway epithelial barrier function and cell-cell contact recovery

    NARCIS (Netherlands)

    Heijink, I H; Brandenburg, S M; Postma, D S; van Oosterhout, A J M

    2012-01-01

    Cigarette smoking, the major cause of chronic obstructive pulmonary disease (COPD), induces aberrant airway epithelial structure and function. The underlying mechanisms are unresolved so far. We studied effects of cigarette smoke extract (CSE) on epithelial barrier function and wound regeneration in

  13. Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.

    Science.gov (United States)

    Shkumatov, Artem; Thompson, Michael; Choi, Kyoung M; Sicard, Delphine; Baek, Kwanghyun; Kim, Dong Hyun; Tschumperlin, Daniel J; Prakash, Y S; Kong, Hyunjoon

    2015-06-01

    Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs.

  14. Store-operated Ca2+ channels in airway epithelial cell function and implications for asthma

    Science.gov (United States)

    Samanta, Krishna; Parekh, Anant B.

    2016-01-01

    The epithelial cells of the lung are at the interface of a host and its environment and are therefore directly exposed to the inhaled air-borne particles. Rather than serving as a simple physical barrier, airway epithelia detect allergens and other irritants and then help organize the subsequent immune response through release of a plethora of secreted signals. Many of these signals are generated in response to opening of store-operated Ca2+ channels in the plasma membrane. In this review, we describe the properties of airway store-operated channels and their role in regulating airway epithelial cell function. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377718

  15. Long acting β2-agonist and corticosteroid restore airway glandular cell function altered by bacterial supernatant

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    Nawrocki-Raby Béatrice

    2010-01-01

    Full Text Available Abstract Background Staphylococcus aureus releases virulence factors (VF that may impair the innate protective functions of airway cells. The aim of this study was to determine whether a long-acting β2 adrenergic receptor agonist (salmeterol hydroxynaphthoate, Sal combined with a corticosteroid (fluticasone propionate, FP was able to regulate ion content and cytokine expression by airway glandular cells after exposure to S. aureus supernatant. Methods A human airway glandular cell line was incubated with S. aureus supernatant for 1 h and then treated with the combination Sal/FP for 4 h. The expression of actin and CFTR proteins was analyzed by immunofluorescence. Videomicroscopy was used to evaluate chloride secretion and X-ray microanalysis to measure the intracellular ion and water content. The pro-inflammatory cytokine expression was assessed by RT-PCR and ELISA. Results When the cells were incubated with S. aureus supernatant and then with Sal/FP, the cellular localisation of CFTR was apical compared to the cytoplasmic localisation in cells incubated with S. aureus supernatant alone. The incubation of airway epithelial cells with S. aureus supernatant reduced by 66% the chloride efflux that was fully restored by Sal/FP treatment. We also observed that Sal/FP treatment induced the restoration of ion (Cl and S and water content within the intracellular secretory granules of airway glandular cells and reduced the bacterial supernatant-dependent increase of pro-inflammatory cytokines IL8 and TNFα. Conclusions Our results demonstrate that treatment with the combination of a corticosteroid and a long-acting β2 adrenergic receptor agonist after bacterial infection restores the airway glandular cell function. Abnormal mucus induced by defective ion transport during pulmonary infection could benefit from treatment with a combination of β2 adrenergic receptor agonist and glucocorticoid.

  16. Defining an olfactory receptor function in airway smooth muscle cells

    Science.gov (United States)

    Aisenberg, William H.; Huang, Jessie; Zhu, Wanqu; Rajkumar, Premraj; Cruz, Randy; Santhanam, Lakshmi; Natarajan, Niranjana; Yong, Hwan Mee; De Santiago, Breann; Oh, Jung Jin; Yoon, A-Rum; Panettieri, Reynold A.; Homann, Oliver; Sullivan, John K.; Liggett, Stephen B.; Pluznick, Jennifer L.; An, Steven S.

    2016-01-01

    Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma. PMID:27905542

  17. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma.

    Science.gov (United States)

    An, S S; Bai, T R; Bates, J H T; Black, J L; Brown, R H; Brusasco, V; Chitano, P; Deng, L; Dowell, M; Eidelman, D H; Fabry, B; Fairbank, N J; Ford, L E; Fredberg, J J; Gerthoffer, W T; Gilbert, S H; Gosens, R; Gunst, S J; Halayko, A J; Ingram, R H; Irvin, C G; James, A L; Janssen, L J; King, G G; Knight, D A; Lauzon, A M; Lakser, O J; Ludwig, M S; Lutchen, K R; Maksym, G N; Martin, J G; Mauad, T; McParland, B E; Mijailovich, S M; Mitchell, H W; Mitchell, R W; Mitzner, W; Murphy, T M; Paré, P D; Pellegrino, R; Sanderson, M J; Schellenberg, R R; Seow, C Y; Silveira, P S P; Smith, P G; Solway, J; Stephens, N L; Sterk, P J; Stewart, A G; Tang, D D; Tepper, R S; Tran, T; Wang, L

    2007-05-01

    Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling. Anti-inflammatory therapy, however, does not "cure" asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM. In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored.

  18. Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function.

    Science.gov (United States)

    Paganin, Patrizia; Fiscarelli, Ersilia Vita; Tuccio, Vanessa; Chiancianesi, Manuela; Bacci, Giovanni; Morelli, Patrizia; Dolce, Daniela; Dalmastri, Claudia; De Alessandri, Alessandra; Lucidi, Vincenzina; Taccetti, Giovanni; Mengoni, Alessio; Bevivino, Annamaria

    2015-01-01

    Cystic fibrosis (CF) is a genetic disease resulting in chronic polymicrobial infections of the airways and progressive decline in lung function. To gain insight into the underlying causes of severe lung diseases, we aimed at comparing the airway microbiota detected in sputum of CF patients with stable lung function (S) versus those with a substantial decline in lung function (SD). Microbiota composition was investigated by using culture-based and culture-independent methods, and by performing multivariate and statistical analyses. Culture-based methods identified some microbial species associated with a worse lung function, i.e. Pseudomonas aeruginosa, Rothia mucilaginosa, Streptococcus pneumoniae and Candida albicans, but only the presence of S. pneumoniae and R. mucilaginosa was found to be associated with increased severe decline in forced expiratory volume in 1 second (FEV1). Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis revealed a higher bacterial diversity than that detected by culture-based methods. Molecular signatures with a statistically significant odds ratio for SD status were detected, and classified as Pseudomonas, Burkholderia and Shewanella, while for other Terminal Restriction Fragments (T-RFs) no species assignation was achieved. The analysis of T-RFLP data using ecological biodiversity indices showed reduced Evenness in SD patients compared to S ones, suggesting an impaired ecology of the bacterial community in SD patients. Statistically significant differences of the ecological biodiversity indices among the three sub-groups of FEV1 (normal/mild vs moderate vs severe) were also found, suggesting that the patients with moderate lung disease experienced changes in the airway assembly of taxa. Overall, changes in CF airway microbial community associated with a severe lung function decline were detected, allowing us to define some discriminatory species as well as some discriminatory T-RFs that represent good candidates for the

  19. Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function.

    Directory of Open Access Journals (Sweden)

    Patrizia Paganin

    Full Text Available Cystic fibrosis (CF is a genetic disease resulting in chronic polymicrobial infections of the airways and progressive decline in lung function. To gain insight into the underlying causes of severe lung diseases, we aimed at comparing the airway microbiota detected in sputum of CF patients with stable lung function (S versus those with a substantial decline in lung function (SD. Microbiota composition was investigated by using culture-based and culture-independent methods, and by performing multivariate and statistical analyses. Culture-based methods identified some microbial species associated with a worse lung function, i.e. Pseudomonas aeruginosa, Rothia mucilaginosa, Streptococcus pneumoniae and Candida albicans, but only the presence of S. pneumoniae and R. mucilaginosa was found to be associated with increased severe decline in forced expiratory volume in 1 second (FEV1. Terminal-Restriction Fragment Length Polymorphism (T-RFLP analysis revealed a higher bacterial diversity than that detected by culture-based methods. Molecular signatures with a statistically significant odds ratio for SD status were detected, and classified as Pseudomonas, Burkholderia and Shewanella, while for other Terminal Restriction Fragments (T-RFs no species assignation was achieved. The analysis of T-RFLP data using ecological biodiversity indices showed reduced Evenness in SD patients compared to S ones, suggesting an impaired ecology of the bacterial community in SD patients. Statistically significant differences of the ecological biodiversity indices among the three sub-groups of FEV1 (normal/mild vs moderate vs severe were also found, suggesting that the patients with moderate lung disease experienced changes in the airway assembly of taxa. Overall, changes in CF airway microbial community associated with a severe lung function decline were detected, allowing us to define some discriminatory species as well as some discriminatory T-RFs that represent good

  20. Pycnogenol Ameliorates Asthmatic Airway Inflammation and Inhibits the Function of Goblet Cells.

    Science.gov (United States)

    Liu, Zhaoe; Han, Bo; Chen, Xing; Wu, Qiaoling; Wang, Lijun; Li, Gang

    2016-11-01

    Pycnogenol(®) (PYC) is utilized in the treatment of various diseases ranging from chronic inflammation to circulatory diseases, but its efficacy and functional mechanism in pediatric asthma continue to remain obscure. Therefore, the purpose of this study was to investigate the effectiveness and molecular mechanism of PYC on regulation of asthmatic airway inflammation. We found that PYC with tail intravenous injection of 50 mg/kg or intragastric administration of 100 mg/kg all reduced ovalbumin (OVA)-induced airway injury. Pharmacokinetics of PYC was evaluated by high-performance liquid chromatography assay, indicating that PYC was quickly absorbed into the blood after intragastric administration, and PYC metabolism was later improved gradually with increase of time after PYC administration. PYC has a higher bioavailability of 71.96%, and it was more easily absorbed by the body. PYC inhibited the number of total inflammatory cells and levels of interleukin (IL)-4, IL-5, IL-9, and IL-13 in bronchoalveolar lavage fluid of OVA-induced mice. PYC inhibited IL-13 secretion from the Th2 cells, thereby causing a reduction in expression of the signaling molecules in JAK/STAT6 pathway in airway epithelial cells. STAT6 silence suppressed IL-13-increased acetylcholine level. STAT6 overexpression promoted expression of goblet cell metaplasia-associated molecules (FOXA3, SPDEF, and Muc5ac). PYC suppressed OVA-induced expression of FOXA3, SPDEF, and Muc5ac in lung. Our findings indicate that PYC has a higher bioavailability and it prevents emergence of OVA-induced airway injury and airway inflammation in mice by inhibiting IL-13/JAK/STAT6 pathway and blocking release of acetylcholine to reduce goblet cell metaplasia.

  1. Effects of Salmeterol and Fluticasone Propionate Combination versus Fluticasone Propionate on Airway Function and Eosinophilic Inflammation in Mild Asthma

    Directory of Open Access Journals (Sweden)

    Makoto Hoshino

    2009-01-01

    Conclusions: These findings suggest that SFC is more useful than FP in mild asthma cases. The clinical benefit of SFC provides evidence that IOS and induced sputum allows for the detection of changes in airway function and inflammation.

  2. The loss of Hoxa5 function promotes Notch-dependent goblet cell metaplasia in lung airways

    Directory of Open Access Journals (Sweden)

    Olivier Boucherat

    2012-05-01

    Hox genes encode transcription factors controlling complex developmental processes in various organs. Little is known, however, about how HOX proteins control cell fate. Herein, we demonstrate that the goblet cell metaplasia observed in lung airways from Hoxa5−/− mice originates from the transdifferentiation of Clara cells. Reduced CC10 expression in Hoxa5−/− embryos indicates that altered cell specification occurs prior to birth. The loss of Hoxa5 function does not preclude airway repair after naphthalene exposure, but the regenerated epithelium presents goblet cell metaplasia and less CC10-positive cells, demonstrating the essential role of Hoxa5 for correct differentiation. Goblet cell metaplasia in Hoxa5−/− mice is a FOXA2-independent process. However, it is associated with increased Notch signaling activity. Consistent with these findings, expression levels of activated NOTCH1 and the effector gene HEY2 are enhanced in patients with chronic obstructive pulmonary disease. In vivo administration of a γ-secretase inhibitor attenuates goblet cell metaplasia in Hoxa5−/− mice, highlighting the contribution of Notch signaling to the phenotype and suggesting a potential therapeutic strategy to inhibit goblet cell differentiation and mucus overproduction in airway diseases. In summary, the loss of Hoxa5 function in lung mesenchyme impacts on epithelial cell fate by modulating Notch signaling.

  3. Airway smooth muscle phenotype and function : interactions with current asthma therapies

    NARCIS (Netherlands)

    Halayko, A J; Tran, T; Ji, S Y; Yamasaki, A; Gosens, R

    2006-01-01

    Asthma incidence has climbed markedly in the past two decades despite an increased use of medications that suppress airway inflammation and repress contraction of smooth muscle that encircles the airways. Asthmatics exhibit episodes of airway inflammation that potentiates reversible airway smooth mu

  4. [Functional anatomy of the central nervous system].

    Science.gov (United States)

    Krainik, A; Feydy, A; Colombani, J M; Hélias, A; Menu, Y

    2003-03-01

    The central nervous system (CNS) has a particular regional functional anatomy. The morphological support of cognitive functions can now be depicted using functional imaging. Lesions of the central nervous system may be responsible of specific symptoms based on their location. Current neuroimaging techniques are able to show and locate precisely macroscopic lesions. Therefore, the knowledge of functional anatomy of the central nervous system is useful to link clinical disorders to symptomatic lesions. Using radio-clinical cases, we present the functional neuro-anatomy related to common cognitive impairments.

  5. Evidence of improved small airways function after azithromycin treatment in diffuse panbronchiolitis.

    Science.gov (United States)

    Hanon, Shane; Verbanck, Sylvia; Schuermans, Daniel; Vanden Berghe, Bram; Vanderhelst, Eef; Vincken, Walter

    2012-01-01

    A 67-year-old never-smoker was diagnosed with diffuse panbronchiolitis (DPB) and was started on 250 mg azithromycin twice weekly. Over a 16-month observation period, lung function was assessed monthly, including a dedicated small airways test, the multiple breath nitrogen washout (MBW) with indices S(cond) and S(acin) of ventilation heterogeneity at the level of the conductive and acinar air spaces, respectively. Baseline measurements indicated moderate airway obstruction, air trapping and considerable dysfunction of the small airways around the acinar entrance. Treatment resulted in excellent symptomatic improvement paralleled by marked improvements in FEV(1), FVC, RV/TLC, S(cond) and S(acin); by contrast, there were no consistent changes in FEF(75) or TL(CO). While improvements were such that S(cond) fell within normal limits after 5 months, S(acin) remained abnormal even after 16 months of treatment. This suggests a distinct acinar structural abnormality in DPB that cannot be reversed by azithromycin.

  6. A new removable airway stent

    Directory of Open Access Journals (Sweden)

    Tore Amundsen

    2016-09-01

    Full Text Available Background: Malignant airway obstruction is a feared complication and will most probably occur more frequently in the future because of increasing cancer incidence and increased life expectancy in cancer patients. Minimal invasive treatment using airway stents represents a meaningful and life-saving palliation. We present a new removable airway stent for improved individualised treatment. Methods: To our knowledge, the new airway stent is the world's first knitted and uncovered self-expanding metal stent, which can unravel and be completely removed. In an in vivo model using two anaesthetised and spontaneously breathing pigs, we deployed and subsequently removed the stents by unravelling the device. The procedures were executed by flexible bronchoscopy in an acute and a chronic setting – a ‘proof-of-principle’ study. Results: The new stent was easily and accurately deployed in the central airways, and it remained fixed in its original position. It was easy to unravel and completely remove from the airways without clinically significant complications. During the presence of the stent in the chronic study, granulation tissue was induced. This tissue disappeared spontaneously with the removal. Conclusions: The new removable stent functioned according to its purpose and unravelled easily, and it was completely removed without significant technical or medical complications. Induced granulation tissue disappeared spontaneously. Further studies on animals and humans are needed to define its optimal indications and future use.

  7. Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Satoshi Konishi

    2016-01-01

    Full Text Available Multi-ciliated airway cells (MCACs play a role in mucociliary clearance of the lung. However, the efficient induction of functional MCACs from human pluripotent stem cells has not yet been reported. Using carboxypeptidase M (CPM as a surface marker of NKX2-1+-ventralized anterior foregut endoderm cells (VAFECs, we report a three-dimensional differentiation protocol for generating proximal airway epithelial progenitor cell spheroids from CPM+ VAFECs. These spheroids could be induced to generate MCACs and other airway lineage cells without alveolar epithelial cells. Furthermore, the directed induction of MCACs and of pulmonary neuroendocrine lineage cells was promoted by adding DAPT, a Notch pathway inhibitor. The induced MCACs demonstrated motile cilia with a “9 + 2” microtubule arrangement and dynein arms capable of beating and generating flow for mucociliary transport. This method is expected to be useful for future studies on human airway disease modeling and regenerative medicine.

  8. P2X7 receptor and caspase 1 activation are central to airway inflammation observed after exposure to tobacco smoke.

    Directory of Open Access Journals (Sweden)

    Suffwan Eltom

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is a cigarette smoke (CS-driven inflammatory airway disease with an increasing global prevalence. Currently there is no effective medication to stop the relentless progression of this disease. It has recently been shown that an activator of the P2X7/inflammasome pathway, ATP, and the resultant products (IL-1β/IL-18 are increased in COPD patients. The aim of this study was to determine whether activation of the P2X7/caspase 1 pathway has a functional role in CS-induced airway inflammation. Mice were exposed to CS twice a day to induce COPD-like inflammation and the role of the P2X7 receptor was investigated. We have demonstrated that CS-induced neutrophilia in a pre-clinical model is temporally associated with markers of inflammasome activation, (increased caspase 1 activity and release of IL-1β/IL-18 in the lungs. A selective P2X7 receptor antagonist and mice genetically modified so that the P2X7 receptors were non-functional attenuated caspase 1 activation, IL-1β release and airway neutrophilia. Furthermore, we demonstrated that the role of this pathway was not restricted to early stages of disease development by showing increased caspase 1 activation in lungs from a more chronic exposure to CS and from patients with COPD. This translational data suggests the P2X7/Inflammasome pathway plays an ongoing role in disease pathogenesis. These results advocate the critical role of the P2X7/caspase 1 axis in CS-induced inflammation, highlighting this as a possible therapeutic target in combating COPD.

  9. The acute remedy of malignant central airway obstruction%大气道癌性梗阻的急性救治

    Institute of Scientific and Technical Information of China (English)

    Kaibao Han; Dong Wang; Dongming Lu; Xiangdong Sun; Hongzhi Sun; Yuan Zhou; Gang Xu; Chuansheng Zhang

    2009-01-01

    Objective: To explore the palliative methods to patients with central airway obstruction due to advanced ma-lignancies. Methods: Twenty-seven patients with carcinous airway obstruction and respiratory distress were emergency remedied, including 12 cases with atelectasis and 23 with pulmonary infection. Soft cryoablated probe of CO2 and/or reticulate endobronchial stent with filmed titanium alloy were placed to the neoplasm following by bronchofibroscope. Results: Totally there were 21 patients achieved completely remission, including airway obstruction, respiratory distress and pulmonary infec-tion remission, and 3 cases got partial remission. Meanwhile there were 3 cases died, in which one was happened during the period of endobronchial stent making, another one with heavy airway obstruction died due to asphyxia 24 h after the operation of brenchofibroscope examination, and the last one with knob invaded died because of hemoptysis and asthema secondarily 36 h after stent placed. Conclusion: The emergency remedy using soft cryoablated probe of CO2 and/or reticulate endobron-chial stent with filmed titanium alloy placed to the neoplasm following by bronchofibroscope to patients with malignant central airway obstruction was a effective salvage method and could prolong patients' lifespan for more subsequent therapeutic opportunities.

  10. Central auditory function of deafness genes.

    Science.gov (United States)

    Willaredt, Marc A; Ebbers, Lena; Nothwang, Hans Gerd

    2014-06-01

    The highly variable benefit of hearing devices is a serious challenge in auditory rehabilitation. Various factors contribute to this phenomenon such as the diversity in ear defects, the different extent of auditory nerve hypoplasia, the age of intervention, and cognitive abilities. Recent analyses indicate that, in addition, central auditory functions of deafness genes have to be considered in this context. Since reduced neuronal activity acts as the common denominator in deafness, it is widely assumed that peripheral deafness influences development and function of the central auditory system in a stereotypical manner. However, functional characterization of transgenic mice with mutated deafness genes demonstrated gene-specific abnormalities in the central auditory system as well. A frequent function of deafness genes in the central auditory system is supported by a genome-wide expression study that revealed significant enrichment of these genes in the transcriptome of the auditory brainstem compared to the entire brain. Here, we will summarize current knowledge of the diverse central auditory functions of deafness genes. We furthermore propose the intimately interwoven gene regulatory networks governing development of the otic placode and the hindbrain as a mechanistic explanation for the widespread expression of these genes beyond the cochlea. We conclude that better knowledge of central auditory dysfunction caused by genetic alterations in deafness genes is required. In combination with improved genetic diagnostics becoming currently available through novel sequencing technologies, this information will likely contribute to better outcome prediction of hearing devices.

  11. Inflammatory airway features and hypothalamic-pituitary adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    CAI Cui; CAO Yu-xue; ZHANG Hong-ying; LE Jing-jing; DONG Jing-cheng; CUI Yan; XU Chang-qing; LIU Bao-jun; WU Jin-feng; DUAN Xiao-hong

    2010-01-01

    Background Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.Methods Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD+BA.These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.Results The inflammatory airway features and HPA axis function in rats in the COPD+BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P <0.05).Conclusions BN rat can be used as an animal model of COPD+BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.

  12. Airway smooth muscle cell tone amplifies contractile function in the presence of chronic cyclic strain.

    Science.gov (United States)

    Fairbank, Nigel J; Connolly, Sarah C; Mackinnon, James D; Wehry, Kathrin; Deng, Linhong; Maksym, Geoffrey N

    2008-09-01

    Chronic contractile activation, or tone, in asthma coupled with continuous stretching due to breathing may be involved in altering the contractile function of airway smooth muscle (ASM). Previously, we (11) showed that cytoskeletal remodeling and stiffening responses to acute (2 h) localized stresses were modulated by the level of contractile activation of ASM. Here, we investigated if altered contractility in response to chronic mechanical strain was dependent on repeated modulation of contractile tone. Cultured human ASM cells received 5% cyclic (0.3 Hz), predominantly uniaxial strain for 5 days, with once-daily dosing of either sham, forskolin, carbachol, or histamine to alter tone. Stiffness, contractility (KCl), and "relaxability" (forskolin) were then measured as was cell alignment, myosin light-chain phosphorylation (pMLC), and myosin light-chain kinase (MLCK) content. Cells became aligned and baseline stiffness increased with strain, but repeated lowering of tone inhibited both effects (P negative tone-modulation dependence of MLCK, observed in static conditions in agreement with previous reports, with strain and tone together increasing both MLCK and pMLC. Furthermore, contractility increased 176% (SE 59) with repeated tone elevation. These findings indicate that with strain, and not without, repeated tone elevation promoted contractile function through changes in cytoskeletal organization and increased contractile protein. The ability of repeated contractile activation to increase contractility, but only with mechanical stretching, suggests a novel mechanism for increased ASM contractility in asthma and for the role of continuous bronchodilator and corticosteroid therapy in reversing airway hyperresponsiveness.

  13. Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

    Institute of Scientific and Technical Information of China (English)

    Yuan Wang; Kairui Mao; Shuhui Sun; Guomei Lin; Xiaodong Wu; Gang Yao; Bing Sun

    2009-01-01

    It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin (TCS) could induce airway inflammation even without the help of alum. Further-more, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accu-mulation of IL-4-producing eosinophiis in peritoneum at an early stage and the adjuvant function of TCS was elimi-nated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4-deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-type adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.

  14. Airway compromise during central venous cannulation in an undiagnosed tubercular retropharyngeal abscess: A case report

    Directory of Open Access Journals (Sweden)

    Sujay Samanta

    2015-01-01

    Full Text Available Central venous cannulation is often associated with complications during insertion even by expert′s hand and with the aid of ultrasound. We encountered a patient for central line insertion through the right internal jugular vein having a retropharyngeal abscess of tubercular origin. We accidentally punctured the abscess cavity leading to increased respiratory distress and subsequent need of intubation to the patient. This kind of complication during central line insertion has never been reported before. We intend to report such a case to alert everyone about the grave complications it can lead to and the methods to minimize them in the times ahead.

  15. Accelerated decline in lung function in smoking women with airway obstruction: SAPALDIA 2 cohort study

    Directory of Open Access Journals (Sweden)

    Zemp Elisabeth

    2005-05-01

    Full Text Available Abstract Background The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women. Methods In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults current smokers in 1991 (18 – 60 yrs were reassessed in 2002 (n = 1792. Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years. Results In both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1 was -10.4 mL(95%CI -15.3, -5.5 per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1 in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05 but this was not seen in men (-14.3 vs -8.8 mL p = 0.49. Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1 was three fold higher in participants with FEV1/FVC Conclusion There are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.

  16. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    -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......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...... in causing airway narrowing, the latter most likely due to loss of elastic recoil of surrounding tissue....

  17. Role of dystrophin in airway smooth muscle phenotype, contraction and lung function.

    Directory of Open Access Journals (Sweden)

    Pawan Sharma

    Full Text Available Dystrophin links the transmembrane dystrophin-glycoprotein complex to the actin cytoskeleton. We have shown that dystrophin-glycoprotein complex subunits are markers for airway smooth muscle phenotype maturation and together with caveolin-1, play an important role in calcium homeostasis. We tested if dystrophin affects phenotype maturation, tracheal contraction and lung physiology. We used dystrophin deficient Golden Retriever dogs (GRMD and mdx mice vs healthy control animals in our approach. We found significant reduction of contractile protein markers: smooth muscle myosin heavy chain (smMHC and calponin and reduced Ca2+ response to contractile agonist in dystrophin deficient cells. Immunocytochemistry revealed reduced stress fibers and number of smMHC positive cells in dystrophin-deficient cells, when compared to control. Immunoblot analysis of Akt1, GSK3β and mTOR phosphorylation further revealed that downstream PI3K signaling, which is essential for phenotype maturation, was suppressed in dystrophin deficient cell cultures. Tracheal rings from mdx mice showed significant reduction in the isometric contraction to methacholine (MCh when compared to genetic control BL10ScSnJ mice (wild-type. In vivo lung function studies using a small animal ventilator revealed a significant reduction in peak airway resistance induced by maximum concentrations of inhaled MCh in mdx mice, while there was no change in other lung function parameters. These data show that the lack of dystrophin is associated with a concomitant suppression of ASM cell phenotype maturation in vitro, ASM contraction ex vivo and lung function in vivo, indicating that a linkage between the DGC and the actin cytoskeleton via dystrophin is a determinant of the phenotype and functional properties of ASM.

  18. Phase contrast X-ray imaging for the non-invasive detection of airway surfaces and lumen characteristics in mouse models of airway disease

    Energy Technology Data Exchange (ETDEWEB)

    Siu, K.K.W. [School of Physics, Monash University, Victoria 3800 (Australia); Monash Centre for Synchrotron Science, Monash University, Victoria 3800 (Australia)], E-mail: Karen.Siu@sync.monash.edu.au; Morgan, K.S.; Paganin, D.M. [School of Physics, Monash University, Victoria 3800 (Australia); Boucher, R. [CF Research and Treatment Center, University of North Carolina at Chapel Hill (United States); Uesugi, K.; Yagi, N. [SPring-8/JASRI, Hyogo 679-5198 (Japan); Parsons, D.W. [Department of Pulmonary Medicine, Women' s and Children' s Hospital, South Australia 5006 (Australia); Department of Paediatrics, University of Adelaide, South Australia, 5006 (Australia); Women' s and Children' s Health Research Institute, South Australia, 5006 (Australia)

    2008-12-15

    We seek to establish non-invasive imaging able to detect and measure aspects of the biology and physiology of surface fluids present on airways, in order to develop novel outcome measures able to validate the success of proposed genetic or pharmaceutical therapies for cystic fibrosis (CF) airway disease. Reduction of the thin airway surface liquid (ASL) is thought to be a central pathophysiological process in CF, causing reduced mucociliary clearance that supports ongoing infection and destruction of lung and airways. Current outcome measures in animal models, or humans, are insensitive to the small changes in ASL depth that ought to accompany successful airway therapies. Using phase contrast X-ray imaging (PCXI), we have directly examined the airway surfaces in the nasal airways and tracheas of anaesthetised mice, currently to a resolution of {approx}2 {mu}m. We have also achieved high resolution three-dimensional (3D) imaging of the small airways in mice using phase-contrast enhanced computed tomography (PC-CT) to elucidate the structure-function relationships produced by airway disease. As the resolution of these techniques improves they may permit non-invasive monitoring of changes in ASL depth with therapeutic intervention, and the use of 3D airway and imaging in monitoring of lung health and disease. Phase contrast imaging of airway surfaces has promise for diagnostic and monitoring options in animal models of CF, and the potential for future human airway imaging methodologies is also apparent.

  19. Assessment of airway function in young children with asthma: comparison of spirometry, interrupter technique, and tidal flow by inductance plethsmography.

    Science.gov (United States)

    Black, J; Baxter-Jones, A D G; Gordon, J; Findlay, A L; Helms, P J

    2004-06-01

    The assessment of airway function in young children requires adaptation of techniques designed for adults and/or application of techniques that do not require complex respiratory maneuvers. We sought to assess two methods of measuring airway function: time to peak expiratory flows as a ratio of expiratory time (T(PTEF)/T(E)), derived from respiratory inductance plethysmography, and total respiratory resistance by the interrupter technique (Rint), both obtained during quiet tidal breathing. Both techniques were referenced to FEV1 and flow at 50% expired volume (FEF50) from conventional spirometry in 30 children aged 4-8 years (median age, 6.9; range, 4.5-8.5 years) with a physician diagnosis of asthma and who were able to perform FEV1 with a repeatability of at least 8%. T(PTEF)/T(E) and Rint were performed in random order followed by spirometry, in order to reduce the possible effects of pulmonary stretch on tidal breathing measures. Coefficients of variation (CV) and mean absolute change/baseline standard deviation were derived for each measurement. Baseline FEV1 did not correlate significantly with T(PTEF)/T(E) (r = 0.025), but did correlate with Rint (r = 0.737, P inductance plethysmography does not detect mild airway obstruction or modest changes in airway caliber following bronchodilator in young children with asthma. The interrupter technique may have a role in assessing baseline airway function and response to therapy in children unable to perform reliable spirometry, and/or when the investigator wishes to avoid the possible influence of forced maneuvers on airway tone.

  20. Central functions of the orexinergic system

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yang Zhang; Lei Yu; Qian-Xing Zhuang; Jing-Ning Zhu; Jian-Jun Wang

    2013-01-01

    The neuropeptide orexin is synthesized by neurons exclusively located in the hypothalamus.However,these neurons send axons over virtually the entire brain and spinal cord and therefore constitute a unique central orexinergic system.It is well known that central orexin plays a crucial role in the regulation of various basic non-somatic and somatic physiological functions,including feeding,energy homeostasis,the sleep/wake cycle,reward,addiction,and neuroendocrine,as well as motor control.Moreover,the absence of orexin results in narcolepsy-cataplexy,a simultaneous somatic and non-somatic dysfunction.In this review,we summarize these central functions of the orexinergic system and associated diseases,and suggest that this system may hold a key position in somatic-non-somatic integration.

  1. Engineering Airway Epithelium

    Directory of Open Access Journals (Sweden)

    John P. Soleas

    2012-01-01

    Full Text Available Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990. In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium.

  2. Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough

    Directory of Open Access Journals (Sweden)

    Zhan-Wei Hu

    2016-01-01

    Conclusions: Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.

  3. Phosphodiesterase 4B is essential for TH2-cell function and development of airway hyperresponsiveness in allergic asthma

    Science.gov (United States)

    Catherine Jin, S.-L.; Goya, Sho; Nakae, Susumu; Wang, Dan; Bruss, Matthew; Hou, Chiaoyin; Umetsu, Dale; Conti, Marco

    2010-01-01

    Background Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined. Objectives We investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and TH2-driven inflammatory responses. Methods Wild-type and PDE4B−/− mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and TH2 cytokine production were determined in cultured bronchial lymph node cells. Results Mice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased TH2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, TH2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the TH1 cytokine IFN-γ was not affected in PDE4B−/− mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation. Conclusion By relieving a cAMP-negative constraint, PDE4B plays an essential role in TH2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment. PMID:21047676

  4. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud

    2012-01-01

    Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway disease

  5. Cigarette smoke impairs airway epithelial barrier function and cell-cell contact recovery.

    Science.gov (United States)

    Heijink, I H; Brandenburg, S M; Postma, D S; van Oosterhout, A J M

    2012-02-01

    Cigarette smoking, the major cause of chronic obstructive pulmonary disease (COPD), induces aberrant airway epithelial structure and function. The underlying mechanisms are unresolved so far. We studied effects of cigarette smoke extract (CSE) on epithelial barrier function and wound regeneration in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBECs) from COPD patients, nonsmokers and healthy smokers. We demonstrate that CSE rapidly and transiently impairs 16HBE barrier function, largely due to disruption of cell-cell contacts. CSE induced a similar, but stronger and more sustained, defect in PBECs. Application of the specific epidermal growth factor receptor (EGFR) inhibitor AG1478 showed that EGFR activation contributes to the CSE-induced defects in both 16HBE cells and PBECs. Furthermore, our data indicate that the endogenous protease calpain mediates these defects through tight junction protein degradation. CSE also delayed the reconstitution of 16HBE intercellular contacts during wound healing and attenuated PBEC barrier function upon wound regeneration. These findings were comparable between PBECs from smokers, healthy smokers and COPD patients. In conclusion, we demonstrate for the first time that CSE reduces epithelial integrity, probably by EGFR and calpain-dependent disruption of intercellular contacts. This may increase susceptibility to environmental insults, e.g. inhaled pathogens. Thus, EGFR may be a promising target for therapeutic strategies to improve mucosal barrier function in cigarette smoking-related disease.

  6. The effect of asthma therapeutics on signalling and transcriptional regulation of airway smooth muscle function

    NARCIS (Netherlands)

    Ammit, Alaina J; Burgess, Janette K; Hirst, Stuart J; Hughes, J Margaret; Kaur, Manminder; Lau, Justine Y; Zuyderduyn, Suzanne

    2009-01-01

    SCOPE OF THE REVIEW: Our knowledge of the multifunctional nature of airway smooth muscle (ASM) has expanded rapidly in the last decade, but the underlying molecular mechanisms and how current therapies for obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD),

  7. Lung Function, Airway Inflammation, and Polycyclic Aromatic Hydrocarbons Exposure in Mexican Schoolchildren

    Science.gov (United States)

    Barraza-Villarreal, Albino; Escamilla-Nuñez, Maria Consuelo; Schilmann, Astrid; Hernandez-Cadena, Leticia; Li, Zheng; Romanoff, Lovisa; Sjödin, Andreas; Del Río-Navarro, Blanca Estela; Díaz-Sanchez, David; Díaz-Barriga, Fernando; Sly, Peter; Romieu, Isabelle

    2015-01-01

    Objective To determine the association of exposure to polycyclic aromatic hydrocarbons (PAHs) with lung function and pH of exhaled breath condensate (EBC) in Mexican schoolchildren. Methods A pilot study was performed in a subsample of 64 schoolchildren from Mexico City. Lung function and pH of EBC were measured and metabolites of PAHs in urine samples were determined. The association was analyzed using robust regression models. Results A 10% increase in the concentrations of 2-hydroxyfluorene was significantly negatively associated with forced expiratory volume in 1 second (−11.2 mL, 95% CI: −22.2 to −0.02), forced vital capacity (−11.6 mL, 95% CI: −22.9 to −0.2), and pH of EBC (−0.035, 95% CI: −0.066 to −0.005). Conclusion Biomarkers of PAHs exposure were inversely associated with lung function and decrease of ph of EBC as a marker of airway inflammation in Mexican schoolchildren. PMID:24500378

  8. Virtual endoscopy of the upper, central and peripheral airways with multirow detector CT; Virtuelle Endoskopie der oberen, zentralen und peripheren Atemwege mit Mehrzeilen-Spiral-CT

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, H.; Dinkel, H.P.; Thoeny, H.; Vock, P. [Institut fuer Diagnostische Radiologie, Universitaetsspital Bern (Switzerland); Gugger, M. [Abteilung fuer Pneumologie, Universitaetsspital Bern (Switzerland)

    2002-09-01

    Virtual endoscopy of the upper, central and peripheral airways (virtual laryngoscopy or virtual bronchoscopy) produces endoluminal images similar to those of fiberoptic endoscopy. In particular, virtual endoscopy is useful for the assessment of endoluminal tumor extent and tracheobronchial stenosis. Especially since the introduction of multirow detector CT, high-resolution virtual-endoscopic images of the airways can be reconstructed. Either surface rendering or volume rendering can be used for realistic depiction of the airways. Semitransparent color-coded volume rendering is advantageous, because adjacent structures can be displayed in addition to endoluminal views. A major advantage of virtual endoscopy over fiberoptic endoscopy is its non-invasiveness. With virtual endoscopy, even a high-grade stenosis is passable, enabling evaluation of the distal airways. Disadvantages are its inability to depict mucosal color and to perform therapeutic maneuvers. In comparison to other CT display modes, virtual endoscopy allows a more realistic assessment of tracheobronchial stenosis than axial CT slices and multiplanar reformats. Virtual endoscopy of the airways can be used complementary to fiberoptic endoscopy before tracheotomy, stent implantation or lung resection and for post-operative follow-up. In the future, virtual airway endoscopy will be increasingly applied for interactive virtual reality guidance of airway procedures such as bronchoscopy and surgery. (orig.) [German] Die virtuelle Endoskopie der oberen, zentralen und peripheren Atemwege (virtuelle Laryngoskopie oder virtuelle Bronchoskopie) erzeugt eine der fiberoptischen Endoskopie vergleichbare Ansicht und kommt insbesondere zur Diagnostik von tracheobronchialen Stenosen und Tumoren mit endoluminaler Ausdehnung zur Anwendung. Vor allem seit Einfuehrung der Mehrzeilen-Spiral-CT lassen sich qualitativ hochwertige Rekonstruktionen der Atemwege erstellen. Das erfolgt entweder mittels Oberflaechenrekonstruktion

  9. Multidetector CT evaluation of central airways stenoses: Comparison of virtual bronchoscopy, minimal-intensity projection, and multiplanar reformatted images

    Directory of Open Access Journals (Sweden)

    Dinesh K Sundarakumar

    2011-01-01

    Full Text Available Aims: To evaluate the diagnostic utility of virtual bronchoscopy, multiplanar reformatted images, and minimal-intensity projection in assessing airway stenoses. Settings and Design: It was a prospective study involving 150 patients with symptoms of major airway disease. Materials and Methods: Fifty-six patients were selected for analysis based on the detection of major airway lesions on fiber-optic bronchoscopy (FB or routine axial images. Comparisons were made between axial images, virtual bronchoscopy (VB, minimal-intensity projection (minIP, and multiplanar reformatted (MPR images using FB as the gold standard. Lesions were evaluated in terms of degree of airway narrowing, distance from carina, length of the narrowed segment and visualization of airway distal to the lesion. Results: MPR images had the highest degree of agreement with FB (Κ = 0.76 in the depiction of degree of narrowing. minIP had the least degree of agreement with FB (Κ = 0.51 in this regard. The distal visualization was best on MPR images (84.2%, followed by axial images (80.7%, whereas FB could visualize the lesions only in 45.4% of the cases. VB had the best agreement with FB in assessing the segment length (Κ = 0.62. Overall there were no statistically significant differences in the measurement of the distance from the carina in the axial, minIP, and MPR images. MPR images had the highest overall degree of confidence, namely, 70.17% (n = 40. Conclusion: Three-dimensional reconstruction techniques were found to improve lesion evaluation compared with axial images alone. The technique of MPR images was the most useful for lesion evaluation and provided additional information useful for surgical and airway interventions in tracheobronchial stenosis. minIP was useful in the overall depiction of airway anatomy.

  10. Functional neuroanatomy of the central noradrenergic system.

    Science.gov (United States)

    Szabadi, Elemer

    2013-08-01

    The central noradrenergic neurone, like the peripheral sympathetic neurone, is characterized by a diffusely arborizing terminal axonal network. The central neurones aggregate in distinct brainstem nuclei, of which the locus coeruleus (LC) is the most prominent. LC neurones project widely to most areas of the neuraxis, where they mediate dual effects: neuronal excitation by α₁-adrenoceptors and inhibition by α₂-adrenoceptors. The LC plays an important role in physiological regulatory networks. In the sleep/arousal network the LC promotes wakefulness, via excitatory projections to the cerebral cortex and other wakefulness-promoting nuclei, and inhibitory projections to sleep-promoting nuclei. The LC, together with other pontine noradrenergic nuclei, modulates autonomic functions by excitatory projections to preganglionic sympathetic, and inhibitory projections to preganglionic parasympathetic neurones. The LC also modulates the acute effects of light on physiological functions ('photomodulation'): stimulation of arousal and sympathetic activity by light via the LC opposes the inhibitory effects of light mediated by the ventrolateral preoptic nucleus on arousal and by the paraventricular nucleus on sympathetic activity. Photostimulation of arousal by light via the LC may enable diurnal animals to function during daytime. LC neurones degenerate early and progressively in Parkinson's disease and Alzheimer's disease, leading to cognitive impairment, depression and sleep disturbance.

  11. Air Pollution, Airway Inflammation, and Lung Function in a Cohort Study of Mexico City Schoolchildren

    Science.gov (United States)

    Barraza-Villarreal, Albino; Sunyer, Jordi; Hernandez-Cadena, Leticia; Escamilla-Nuñez, Maria Consuelo; Sienra-Monge, Juan Jose; Ramírez-Aguilar, Matiana; Cortez-Lugo, Marlene; Holguin, Fernando; Diaz-Sánchez, David; Olin, Anna Carin; Romieu, Isabelle

    2008-01-01

    Background The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. Objective In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. Methods We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (FeNO), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. Results An increase of 17.5 μg/m3 in the 8-hr moving average of PM2.5 levels (interquartile range) was associated with a 1.08-ppb increase in FeNO [95% confidence interval (CI), 1.01–1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98–1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00–1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter < 2.5 μm in aerodynamic diamter (PM2.5) was significantly inversely associated with forced expiratory volume in 1 sec (FEV1) (p = 0.048) and forced vital capacity (FVC) (p = 0.012) in asthmatic children and with FVC (p = 0.021) in nonasthmatic children. FeNO and FEV1 were inversely associated (p = 0.005) in asthmatic children. Conclusions Exposure to PM2.5 resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children. PMID:18560490

  12. 中心性气道狭窄病因分析及治疗%Analysis of etiopathogenesis and therapy in patients with central airway stenosis

    Institute of Scientific and Technical Information of China (English)

    常丹; 程德云; 朱辉; 陈文彬

    2011-01-01

    Objective To retrospectively analyse the causes of central airway stenosis and assess the influence on every therapy. Methods We retrospectively reviewed 180 cases with central airway stenosis in West China Hospital,collected their relevant clinic data, and analysed their etiopathogenesis and the effects of every therapy. Results We have collected totally 180 cases with central airway stenosis. The etiopathogenesis of central airway stenosis can be divided into two groups, the benign stenosis (n = 100)and the malignant stenosis (n = 80). The composition of benign airway stenosis were as follow: tracheobronchial tuberculosis ( n = 60, 60% ), post-tracheostomy ( n = 15, 15% ), tracheobronchial injury ( n = 6, 6% ) , post-intubation ( n = 3,3% ), tracheobronchial anastomotic stricture (n = 3, 3% ), thyroid goiter( n = 3, 3% ). And the most common cause of malignant central airway stenosis is lung bronchogenic carcinoma (n = 33,41.25% ) , the second is adenoid cystic carcinoma (n = 12,15% ), followed by esophageal carcinoma ( n = 19, 23.75% ), and thyroid carcinoma ( n = 8.75% ). In the aspect of therapy,53 patients (29.44%) received the treatment of nitinol stent insertion (among their patients, three cases recived more then or equal to two times stent placement), 36(20% ) patients received Surgical Resection, 20 (11.11%) patients were treated by 23 Argon Plasma Coagulation (APC) treatments, 19 patients (10. 56% ) were treated by 38 Dilation of the Airways treatments. Except 37 patients of death and abandoning therapy, the rest 143 patients were all free of symptoms ( cough, expectoration or dyspea) in different degree. Conclusion In China, the most common cause of benign central airway stenosis is tracheobronchial tuberculosis, and the malignant central airway stenosis is lung bronchogenic carcinoma. It is valuable to determine the etiopathogenesis of central airway stenosis to elect correct treatment modes.%目的 回顾分析中心性

  13. Airway Responsiveness to Psychological Processes in Asthma and Health

    Directory of Open Access Journals (Sweden)

    Thomas eRitz

    2012-09-01

    Full Text Available Psychosocial factors have been found to impact airway pathophysiology in respiratory disease with considerable consistency. Influences on airway mechanics have been studied particularly well. The goal of this article is to review the literature on airway responses to psychological stimulation, discuss potential pathways of influence, and present a well-established emotion-induction paradigm to study airway obstruction elicited by unpleasant stimuli. Observational studies have found systematic associations between lung function and daily mood changes. The laboratory –based paradigm of bronchoconstrictive suggestion has been used successfully to elicit airway obstruction in a substantial proportion of asthmatic individuals. Other studies have demonstrated an enhancement of airway responses to standard airway challenges with exercise, allergens, or methacholine. Standardized emotion-induction techniques have consistently shown airway constriction during unpleasant stimulation, with surgery, blood and injury stimuli being particularly powerful. Findings with various forms of stress induction have been more mixed. A number of methodological factors may account for variability across studies, such as choice of measurement technique, temporal association between stimulation and measurement, and the specific quality and intensity of the stimulus material, in particular the extent of implied action-orientation. Research has also begun to elucidate physiological processes associated with psychologically induced airway responses, with vagal excitation and ventilatory influences being the most likely candidate pathways, whereas the role of specific central nervous system pathways and inflammatory processes has been less studied. The technique of emotion-induction using films has the potential to become a standardized challenge paradigm for the further exploration of airway hyperresponsiveness mediated by central nervous system processes.

  14. Acellular Lung Scaffolds Direct Differentiation of Endoderm to Functional Airway Epithelial Cells: Requirement of Matrix-Bound HS Proteoglycans

    Directory of Open Access Journals (Sweden)

    Sharareh Shojaie

    2015-03-01

    Full Text Available Efficient differentiation of pluripotent cells to proximal and distal lung epithelial cell populations remains a challenging task. The 3D extracellular matrix (ECM scaffold is a key component that regulates the interaction of secreted factors with cells during development by often binding to and limiting their diffusion within local gradients. Here we examined the role of the lung ECM in differentiation of pluripotent cells in vitro and demonstrate the robust inductive capacity of the native lung matrix alone. Extended culture of stem cell-derived definitive endoderm on decellularized lung scaffolds in defined, serum-free medium resulted in differentiation into mature airway epithelia, complete with ciliated cells, club cells, and basal cells with morphological and functional similarities to native airways. Heparitinase I, but not chondroitinase ABC, treatment of scaffolds revealed that the differentiation achieved is dependent on heparan sulfate proteoglycans and its bound factors remaining on decellularized scaffolds.

  15. Functional and structural optimization of the respiratory system of the bat Tadarida brasiliensis (Chiroptera, Molossidae): does airway geometry matter?

    Science.gov (United States)

    Canals, Mauricio; Atala, Cristian; Olivares, Ricardo; Guajardo, Francisco; Figueroa, Daniela P; Sabat, Pablo; Rosenmann, Mario

    2005-10-01

    We studied structure and function of the respiratory system in the bat Tadarida brasiliensis and compared it with those of two species of rodents, Abrothrix andinus and A. olivaceus. Tadarida brasiliensis had lower resting oxygen consumption, but higher maximum oxygen consumption and aerobic scope, than the rodents. The blood-gas barrier of the bat was thinner and its relative lung size was larger; however, alveolar surface density was similar among the three species. In consequence, T. brasiliensis has an oxygen diffusion capacity two or three times higher than that of the rodents. In Tadarida brasiliensis the characteristics of the lung were accompanied by geometrical changes in the proximal airway, such as high physical optimization as a consequence of small variations in the symmetry and the scaling ratio of the bronchial diameters. These may constitute an efficient way to save energy in respiratory mechanics and are the first report of airway adjustments to decrease entropy generation in bats.

  16. Regulation and Functional Significance of Airway Surface Liquid pH

    Directory of Open Access Journals (Sweden)

    Coakley RD

    2001-07-01

    Full Text Available In gastrointestinal tissues, cumulative evidence from both in vivo and in vitro studies suggests a role for the cystic fibrosis transmembrane conductance regulator (CFTR in apical epithelial bicarbonate conductance. Abnormal lumenal acidification is thus hypothesized to play a role in the genesis of cystic fibrosis (CF pancreatic disease. However, consensus regarding CFTR's participation in pH regulation of airway surface liquid (ASL and thus the contribution of ASL pH to the etiology of CF lung disease, is lacking. The absence of data reflects difficulties in both sampling ASL in vivo and modeling ASL biology in vitro. Here we evaluate the evidence in support of a lumenal acidification hypothesis in the CF lung, summarize current knowledge of pH regulation in the normal airway and illustrate how hyper-acidified airway secretions could contribute to the pathogenesis of CF lung disease.

  17. Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.

    Science.gov (United States)

    Clay, Candice C; Maniar-Hew, Kinjal; Gerriets, Joan E; Wang, Theodore T; Postlethwait, Edward M; Evans, Michael J; Fontaine, Justin H; Miller, Lisa A

    2014-01-01

    Exposure to ozone has been associated with increased incidence of respiratory morbidity in humans; however the mechanism(s) behind the enhancement of susceptibility are unclear. We have previously reported that exposure to episodic ozone during postnatal development results in an attenuated peripheral blood cytokine response to lipopolysaccharide (LPS) that persists with maturity. As the lung is closely interfaced with the external environment, we hypothesized that the conducting airway epithelium of neonates may also be a target of immunomodulation by ozone. To test this hypothesis, we evaluated primary airway epithelial cell cultures derived from juvenile rhesus macaque monkeys with a prior history of episodic postnatal ozone exposure. Innate immune function was measured by expression of the proinflammatory cytokines IL-6 and IL-8 in primary cultures established following in vivo LPS challenge or, in response to in vitro LPS treatment. Postnatal ozone exposure resulted in significantly attenuated IL-6 mRNA and protein expression in primary cultures from juvenile animals; IL-8 mRNA was also significantly reduced. The effect of antecedent ozone exposure was modulated by in vivo LPS challenge, as primary cultures exhibited enhanced cytokine expression upon secondary in vitro LPS treatment. Assessment of potential IL-6-targeting microRNAs miR-149, miR-202, and miR-410 showed differential expression in primary cultures based upon animal exposure history. Functional assays revealed that miR-149 is capable of binding to the IL-6 3' UTR and decreasing IL-6 protein synthesis in airway epithelial cell lines. Cumulatively, our findings suggest that episodic ozone during early life contributes to the molecular programming of airway epithelium, such that memory from prior exposures is retained in the form of a dysregulated IL-6 and IL-8 response to LPS; differentially expressed microRNAs such as miR-149 may play a role in the persistent modulation of the epithelial innate

  18. Trehalose-mediated autophagy impairs the anti-viral function of human primary airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qun Wu

    Full Text Available Human rhinovirus (HRV is the most common cause of acute exacerbations of chronic lung diseases including asthma. Impaired anti-viral IFN-λ1 production and increased HRV replication in human asthmatic airway epithelial cells may be one of the underlying mechanisms leading to asthma exacerbations. Increased autophagy has been shown in asthmatic airway epithelium, but the role of autophagy in anti-HRV response remains uncertain. Trehalose, a natural glucose disaccharide, has been recognized as an effective autophagy inducer in mammalian cells. In the current study, we used trehalose to induce autophagy in normal human primary airway epithelial cells in order to determine if autophagy directly regulates the anti-viral response against HRV. We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load. Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5 effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load. Mechanistically, ATG5 protein interacted with retinoic acid-inducible gene I (RIG-I and IFN-β promoter stimulator 1 (IPS-1, two critical molecules involved in the expression of anti-viral interferons. Our results suggest that induction of autophagy in human primary airway epithelial cells inhibits the anti-viral IFN-λ1 expression and facilitates HRV infection. Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations.

  19. Vocal Function and Upper Airway Thermoregulation in Five Different Environmental Conditions

    Science.gov (United States)

    Sandage, Mary J.; Connor, Nadine P.; Pascoe, David D.

    2014-01-01

    Purpose: Phonation threshold pressure and perceived phonatory effort were hypothesized to increase and upper airway temperature to decrease following exposure to cold and/or dry air. Greater changes were expected with mouth versus nose breathing. Method: In a within-participant repeated measures design, 15 consented participants (7 men, 8 women)…

  20. MORPHOLOGICAL FEATURES OF LUNG STRUCTURE AND FUNCTIONAL ACTIVITY OF THE AIRWAYS OF GUINEA PIGS AFTER LONG-TERM EXPOSURE WITH NANOSIZED MAGNETITE A

    Directory of Open Access Journals (Sweden)

    Ye. Ye. Abramenko

    2013-01-01

    Full Text Available The results of study, in which we examined the influence of nanosized magnetite on breath organs histological structure and contractility activity of the airways of guinea pigs by method of mechanography has been presented. In the lungs of experimental animals an inflammatory response developed as a result of long-term inhalation intake of nanosized magnetite. Also the functional status of the airways changed and appeared as changing of amplitude of contractility response under the action of histamine.

  1. Airway management and morbid obesity

    DEFF Research Database (Denmark)

    Kristensen, Michael S

    2010-01-01

    airway and the function of the lungs (decreased residual capacity and aggravated ventilation perfusion mismatch) worse than in lean patients. Proper planning and preparation of airway management is essential, including elevation of the patient's upper body, head and neck. Preoxygenation is mandatory...... 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...... pressure, noninvasive ventilation and physiotherapy....

  2. 22 CFR 94.3 - Functions of the Central Authority.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Functions of the Central Authority. 94.3 Section 94.3 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES INTERNATIONAL CHILD ABDUCTION § 94.3 Functions of the Central Authority. The U.S. Central Authority shall cooperate with...

  3. Chlamydia muridarum infection subverts dendritic cell function to promote Th2 immunity and airways hyperreactivity.

    Science.gov (United States)

    Kaiko, Gerard E; Phipps, Simon; Hickey, Danica K; Lam, Chuan En; Hansbro, Philip M; Foster, Paul S; Beagley, Kenneth W

    2008-02-15

    There is strong epidemiological evidence that Chlamydia infection can lead to exacerbation of asthma. However, the mechanism(s) whereby chlamydial infection, which normally elicits a strong Th type 1 (Th1) immune response, can exacerbate asthma, a disease characterized by dominant Th type 2 (Th2) immune responses, remains unclear. In the present study, we show that Chlamydia muridarum infection of murine bone marrow-derived dendritic cells (BMDC) modulates the phenotype, cytokine secretion profile, and Ag-presenting capability of these BMDC. Chlamydia-infected BMDC express lower levels of CD80 and increased CD86 compared with noninfected BMDC. When infected with Chlamydia, BMDC secrete increased TNF-alpha, IL-6, IL-10, IL-12, and IL-13. OVA peptide-pulsed infected BMDC induced significant proliferation of transgenic CD4(+) DO11.10 (D10) T cells, strongly inhibited IFN-gamma secretion by D10 cells, and promoted a Th2 phenotype. Intratracheal transfer of infected, but not control noninfected, OVA peptide-pulsed BMDC to naive BALB/c mice, which had been i.v. infused with naive D10 T cells, resulted in increased levels of IL-10 and IL-13 in bronchoalveolar lavage fluid. Recipients of these infected BMDC showed significant increases in airways resistance and decreased airways compliance compared with mice that had received noninfected BMDC, indicative of the development of airways hyperreactivity. Collectively, these data suggest that Chlamydia infection of DCs allows the pathogen to deviate the induced immune response from a protective Th1 to a nonprotective Th2 response that could permit ongoing chronic infection. In the setting of allergic airways inflammation, this infection may then contribute to exacerbation of the asthmatic phenotype.

  4. Effect of azithromycin, terbutaline combined with montelukast on airway function and gradient of infection in cough variant asthma children with infection

    Institute of Scientific and Technical Information of China (English)

    Xin-Xin Pei

    2016-01-01

    Objective:To analyze the effect of azithromycin, terbutaline combined with montelukast on airway function and gradient of infection in cough variant asthma children with infection. Methods: A total of 116 cases of cough variant asthma children with infection were included in the study and randomly divided into observation group and control group (n=58), control group received azithromycin treatment, observation group received azithromycin, terbutaline combined with montelukast treatment, and then differences in basic lung function and small airway function, asthma attack and airway remodeling-related indicators, infection-related indicators, etc. were compared between two groups after treatment.Results: Basic lung function indexes FEV1 and FVC of observation group after treatment were significantly higher than those of control group, and small airway function indexes MMEF, FEF50% and FEF75% were significantly lower than those of control group; serum ECP, IgE, IL-5, MMP-2, MMP-9, TIMP-1, PET, CRP and IL-4 levels of observation group after treatment were lower than those of control group while IFN-γ and hBD-1 levels were higher than those of control group.Conclusion:Azithromycin, terbutaline combined with montelukast can improve airway function and infection status and promote disease rehabilitation in cough variant asthma children with infection.

  5. The high affinity IgE receptor (FcεRI) expression and function in airway smooth muscle.

    Science.gov (United States)

    Redhu, Naresh Singh; Gounni, Abdelilah S

    2013-02-01

    The airway smooth muscle (ASM) is no longer considered as merely a contractile apparatus and passive recipient of growth factors, neurotransmitters and inflammatory mediators signal but a critical player in the perpetuation and modulation of airway inflammation and remodeling. In recent years, a molecular link between ASM and IgE has been established through Fc epsilon receptors (FcεRs) in modulating the phenotype and function of these cells. Particularly, the expression of high affinity IgE receptor (FcεRI) has been noted in primary human ASM cells in vitro and in vivo within bronchial biopsies of allergic asthmatic subjects. The activation of FcεRI on ASM cells suggests a critical yet almost completely ignored network which may modulate ASM cell function in allergic asthma. This review is intended to provide a historical perspective of IgE effects on ASM and highlights the recent updates in the expression and function of FcεRI, and to present future perspectives of activation of this pathway in ASM cells.

  6. Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough

    Science.gov (United States)

    Hu, Zhan-Wei; Zhao, Yan-Ni; Cheng, Yuan; Guo, Cui-Yan; Wang, Xi; Li, Nan; Liu, Jun-Qing; Kang, Hui; Xia, Guo-Guang; Hu, Ping; Zhang, Ping-Ji; Ma, Jing; Liu, Ying; Zhang, Cheng; Su, Li; Wang, Guang-Fa

    2016-01-01

    Background: The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. Methods: We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing 200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate (EBC) pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. Results: Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1% −1.54, 95% confidence interval [CI]: −0.20 to −2.89). The odds ratio for chronic cough was 2.54 (95% CI: 1.57–4.10) for category 1 and 1.97 (95% CI: 1.16–3.37) for category 2, compared with category 3. EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] = 0.176, P air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure. PMID:27625090

  7. [Airways and respiratory function: preoperative screening--anaesthetic and intensive care aspects and considerations].

    Science.gov (United States)

    Reber, Adrian

    2009-07-01

    The risk factors for respiratory complications can broadly be classified as patient-related or procedure-related factors. Knowledge about pathophysiological and pharmacological aspects of the patients' condition is essential for their safe care during preoperative assessment, intra-operative management and, if necessary, postoperative intensive care. A good understanding of the risk factors leading to the development of postoperative respiratory complications should result in the implementation of perioperative strategies designed to prevent their occurrence and reduce severity. Special information regarding airway and lung aspects as well as cases involving different types of anaesthesia and surgical procedures are also discussed.

  8. Trimethylangelicin promotes the functional rescue of mutant F508del CFTR protein in cystic fibrosis airway cells.

    Science.gov (United States)

    Favia, Maria; Mancini, Maria T; Bezzerri, Valentino; Guerra, Lorenzo; Laselva, Onofrio; Abbattiscianni, Anna C; Debellis, Lucantonio; Reshkin, Stephan J; Gambari, Roberto; Cabrini, Giulio; Casavola, Valeria

    2014-07-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) carrying the F508del mutation is retained in endoplasmic reticulum and fails to traffic to the cell surface where it functions as a protein kinase A (PKA)-activated chloride channel. Pharmacological correctors that rescue the trafficking of F508del CFTR may overcome this defect; however, the rescued F508del CFTR still displays reduced chloride permeability. Therefore, a combined administration of correctors and potentiators of the gating defect is ideal. We recently found that 4,6,4'-trimethylangelicin (TMA), besides inhibiting the expression of the IL-8 gene in airway cells in which the inflammatory response was challenged with Pseudomonas aeruginosa, also potentiates the cAMP/PKA-dependent activation of wild-type CFTR or F508del CFTR that has been restored to the plasma membrane. Here, we demonstrate that long preincubation with nanomolar concentrations of TMA is able to effectively rescue both F508del CFTR-dependent chloride secretion and F508del CFTR cell surface expression in both primary or secondary airway cell monolayers homozygous for F508del mutation. The correction effect of TMA seems to be selective for CFTR and persisted for 24 h after washout. Altogether, the results suggest that TMA, besides its anti-inflammatory and potentiator activities, also displays corrector properties.

  9. 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...... have become the standard with which to assess emphysema extent but airway abnormalities have so far been more challenging to quantify. Automated methods for analysis are indispensable as the visible airway tree in a CT scan can include several hundreds of individual branches. However, automation...... of scan on airway dimensions in subjects with and without COPD. The results show measured airway dimensions to be affected by differences in the level of inspiration and this dependency is again influenced by COPD. Inspiration level should therefore be accounted for when measuring airways, and airway...

  10. Strangeness production as a function of centrality

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, E. [University of Bergen, Department of Physics, N-5007 Bergen (Norway); Blaes, R.; Cherney, M.; de la Cruz, B.; Fernandez, C.; Garabatos, C.; Garzon, J.A.; Geist, W.M.; Greiner, D.E.; Gruhn, C.; Hafidouni, M.; Hrubec, J.; Jones, P.G.; Judd, E.G.; Kuipers, J.P.M.; Ladrem, M.; Ladron de Guevara, P.; Lovhoiden, G.; MacNaughton, J.; Mosquera, J.; Nathaniec, Z.; Nelson, J.M.; Neuhofer, G.; Perez de los Heros, C.; Plo, M.; Porth, P.; Powell, B.; Ramil, A.; Rohringer, H.; Sakrejda, I.; Thorsteinsen, T.F.; Traxler, J.; Voltolini, C.; Wozniak, K.; Yanez, A.; Zybert, R.; Douglas E. Greiner for the NA36 Collaboration

    1995-07-20

    A correction to the TPC efficiency calculations based on discriminator response data is shown to have an average effect of 20% on the absolute magnitude of the earlier results. Consistency between runs with the NA36 magnet in different polarities is demonstrated. Comparisons are made with NA35 S+Ag data. The absolute flux of {Lambda} particles is approximately a factor of two in disagreement between the two experiments. A dependence of the rapidity spectrum for lambda`s on centrality is demonstrated. {copyright} 1995 {ital American} {ital Institute} {ital of} {ital Physics}.

  11. Initial size of cleft does not correlate with size and function of nasal airway in adults with unilateral cleft lip and palate.

    Science.gov (United States)

    Reiser, Erika; Andlin-Sobocki, Anna; Mani, Maria; Holmström, Mats

    2011-06-01

    The noses of patients with clefts are often functionally inadequate. The aim of the present study was to evaluate the correlation between size of the maxillary cleft in infancy and size and function of the nasal airway in adults with unilateral cleft lip and palate (UCLP). This is a long-term follow up study including 53 patients with UCLP born between 1960 and 1987 and treated at the Cleft Lip and Palate Centre, Uppsala University Hospital, Sweden. Lip repair was performed at 3-4 months of age followed by either a one-stage or a two-stage palatal closure. The size of the cleft was measured on infant maxillary dental casts. Nasal minimum cross-sectional area (cm(2)) and volume (cm(3)) (acoustic rhinometry), air flow resistance (Pa s/cm(3)) (rhinomanometry), peak inspiratory flow (l/min) (peak nasal inspiratory flow) and number of identified odours (Scandinavian odor-identification test) were assessed in adulthood. The size of the maxillary cleft varied considerably at infancy. The size of the nasal airway and its function on the cleft side in adulthood were reduced compared with the non-cleft side, but no correlations were found between size of the initial cleft in infancy and size and function of the nasal airway in adulthood. In adults born with UCLP, therefore, size of the maxillary cleft in infancy does not seem to affect size and function of the nasal airway in adulthood.

  12. X-Ray based Lung Function measurement–a sensitive technique to quantify lung function in allergic airway inflammation mouse models

    Science.gov (United States)

    Dullin, C.; Markus, M. A.; Larsson, E.; Tromba, G.; Hülsmann, S.; Alves, F.

    2016-11-01

    In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

  13. Sexual function and obstructive sleep apnea-hypopnea : A randomized clinical trial evaluating the effects of oral-appliance and continuous positive airway pressure therapy

    NARCIS (Netherlands)

    Hoekema, Aarnoud; Stel, Anna-Lucia; Stegenga, Boudewijn; van der Hoeven, Johannes H.; Wijkstra, Peter J.; van Driel, Mels F.; de Bont, Lambert G. M.

    2007-01-01

    Introduction. The obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with sexual dysfunction. Although successful treatment with continuous positive airway pressure (CPAP) has been demonstrated to improve sexual function, the effects of oral-appliance therapy are unknown. Aim. The aims

  14. Importance of slow vital capacity in the detection of airway obstruction*

    OpenAIRE

    Ana Raquel Goncalves de Barros; Margarida Batista Pires; Nuno Miguel Ferreira Raposo

    2013-01-01

    OBJECTIVE: To investigate the presence of airway obstruction by determining the FEV1/FVC and FEV1/slow vital capacity (SVC) ratios. METHODS: This was a quantitative, retrospective cross-sectional study. The sample comprised 1,084 individuals who underwent spirometry and plethysmography in a central hospital in Lisbon, Portugal. The study sample was stratified into six groups, by pulmonary function. RESULTS: The analysis of the FEV1/FVC ratio revealed the presence of airway obstructio...

  15. Neodymium yttrium-aluminium-garnet laser resection significantly improves quality of life in patients with malignant central airway obstruction due to lung cancer.

    Science.gov (United States)

    Zaric, B; Kovacevic, T; Stojsic, V; Sarcev, T; Kocic, M; Urosevic, M; Kalem, D; Perin, B

    2015-07-01

    Neodymium yttrium-aluminium-garnet (Nd : YAG) laser resection is one of the mostly used interventional pulmonology techniques for urgent desobstruction of malignant central airway obstruction (CAO). The major aim of this trial was to evaluate potential influence of Nd : YAG laser resection on overall quality of life (QoL) in patients with central lung cancer. Patients with malignant CAO scheduled for Nd : YAG laser resection were prospectively recruited in the trial. All patients were given European Organization for Research and Treatment, Quality of Life questionnaire (EORTC QLQ-30 v.3) before the procedure and approximately 2 weeks after the treatment. There were 37 male and 10 female patients, average age 54 ± 10 years. Most common tumour type was adenocarcinoma diagnosed in 51% of patients. Majority of patients were diagnosed in stage IIIB (53.2%) and stage IV (25.5%). Most common Eastern Cooperative Oncology Group performance status was 1 (72.3%). Nd : YAG laser resection significantly improved (Plife, social activities and financial situation, we did not observe statistically significant improvement. Nd : YAG laser resection of malignant CAO significantly improves QoL and overall health in patients with lung cancer.

  16. Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough

    Institute of Scientific and Technical Information of China (English)

    Zhan-Wei Hu; Yan-Ni Zhao; Yuan Cheng; Cui-Yan Guo; Xi Wang; Nan Li; Jun-Qing Liu

    2016-01-01

    Background:The effects of near-road pollution on lung function in China have not been well studied.We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function,airway inflammation,and respiratory symptoms.Methods:We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing.Distances between home addresses and the nearest major roads were measured to calculate home-road distance.We used the distance categories 1,2,and 3,representing <100 m,100-200 m,and >200 m,respectively,as the dose indicator for traffic-related air pollution exposure.Lung function,exhaled breath condensate (EBC) pH,and interleukin 6 levels were measured.As a follow-up,398 participants had a second lung function assessment about 3 years later,and lung function decline was also examined as an outcome.We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms.As the EBC biomarker data were not normally distributed,we performed correlation analysis between home-road distance categories and EBC biomarkers.Results:Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1%-1.54,95% confidence interval [CI]:-0.20 to-2.89).The odds ratio for chronic cough was 2.54 (95% CI.:1.57-4.10) for category 1 and 1.97 (95% CI.:1.16-3.37) for category 2,compared with category 3.EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] =0.176,P < 0.001).Conclusions:Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function,airway acidification,and a higher prevalence of chronic cough.EBC pH is a potential useful biomarker for evaluating air pollution exposure.

  17. Airway Epithelial Orchestration of Innate Immune Function in Response to Virus Infection. A Focus on Asthma.

    Science.gov (United States)

    Ritchie, Andrew I; Jackson, David J; Edwards, Michael R; Johnston, Sebastian L

    2016-03-01

    Asthma is a very common respiratory condition with a worldwide prevalence predicted to increase. There are significant differences in airway epithelial responses in asthma that are of particular interest during exacerbations. Preventing exacerbations is a primary aim when treating asthma because they often necessitate unscheduled healthcare visits and hospitalizations and are a significant cause of morbidity and mortality. The most common cause of asthma exacerbations is a respiratory virus infection, of which the most likely type is rhinovirus infection. This article focuses on the role played by the epithelium in orchestrating the innate immune responses to respiratory virus infection. Recent studies show impaired bronchial epithelial cell innate antiviral immune responses, as well as augmentation of a pro-Th2 response characterized by the epithelial-derived cytokines IL-25 and IL-33, crucial in maintaining the Th2 cytokine response to virus infection in asthma. A better understanding of the mechanisms of these abnormal immune responses has the potential to lead to the development of novel therapeutic targets for virus-induced exacerbations. The aim of this article is to highlight current knowledge regarding the role of viruses and immune modulation in the asthmatic epithelium and to discuss exciting areas for future research and novel treatments.

  18. The effects of emphysema on airway disease: Correlations between multi-detector CT and pulmonary function tests in smokers

    Energy Technology Data Exchange (ETDEWEB)

    Yahaba, Misuzu, E-mail: mis_misuzu@yahoo.co.jp; Kawata, Naoko, E-mail: chumito_03@yahoo.co.jp; Iesato, Ken, E-mail: iesato_k@yahoo.co.jp; Matsuura, Yukiko, E-mail: matsuyuki_future@yahoo.co.jp; Sugiura, Toshihiko, E-mail: sugiura@js3.so-net.ne.jp; Kasai, Hajime, E-mail: daikasai6075@yahoo.co.jp; Sakurai, Yoriko, E-mail: yoliri@nifty.com; Terada, Jiro, E-mail: jirotera@chiba-u.jp; Sakao, Seiichiro, E-mail: sakao@faculty.chiba-u.jp; Tada, Yuji, E-mail: ytada@faculty.chiba-u.jp; Tanabe, Nobuhiro, E-mail: ntanabe@faculty.chiba-u.jp; Tatsumi, Koichiro, E-mail: tatsumi@faculty.chiba-u.jp

    2014-06-15

    Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. Objective: The goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. Methods: Ninety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. Results: In patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV{sub 1.} No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. Conclusions: A significant correlation exists between airway parameters and FEV{sub 1} in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD.

  19. Airway morphology and function of rats following dermal sensitization and respiratory challenge with low molecular weight chemicals

    NARCIS (Netherlands)

    Arts, J.H.E.; Kuper, C.F.; Spoor, S.M.; Bloksma, N.

    1998-01-01

    Local lymph node activation and increased total serum IgE levels are suggested to be predictive parameters of airway hypersensitivity caused by low molecular weight (LMW) chemicals. Whether increases of total serum IgE are indicative of actual induction of specific airway reactions (morphological an

  20. [Peripheral, central and functional vertigo syndromes].

    Science.gov (United States)

    Strupp, M; Dieterich, M; Zwergal, A; Brandt, T

    2015-12-01

    Depending on the temporal course, three forms of vertigo syndrome can be differentiated: 1) vertigo attacks, e.g. benign paroxysmal positional vertigo (BPPV), Menière's disease and vestibular migraine, 2) acute spontaneous vertigo lasting for days, e.g. acute unilateral vestibulopathy, brainstem or cerebellar infarction and 3) symptoms lasting for months or years, e.g. bilateral vestibulopathy and functional vertigo. The specific therapy of the various syndromes is based on three principles: 1) physical treatment with liberatory maneuvers for BPPV and balance training for vestibular deficits, 2) pharmacotherapy, e.g. for acute unilateral vestibulopathy (corticosteroids) and Menière's disease (transtympanic administration of gentamicin or steroids and high-dose betahistine therapy); placebo-controlled pharmacotherapy studies are currently being carried out for acute unilateral vestibulopathy, vestibular paroxysmia, prophylaxis of BPPV, vestibular migraine, episodic ataxia type 2 and cerebellar ataxia; 3) psychotherapy for functional dizziness.

  1. An intranasal selective antisense oligonucleotide impairs lung cyclooxygenase-2 production and improves inflammation, but worsens airway function, in house dust mite sensitive mice

    Directory of Open Access Journals (Sweden)

    Pujols Laura

    2008-11-01

    Full Text Available Abstract Background Despite its reported pro-inflammatory activity, cyclooxygenase (COX-2 has been proposed to play a protective role in asthma. Accordingly, COX-2 might be down-regulated in the airway cells of asthmatics. This, together with results of experiments to assess the impact of COX-2 blockade in ovalbumin (OVA-sensitized mice in vivo, led us to propose a novel experimental approach using house dust mite (HDM-sensitized mice in which we mimicked altered regulation of COX-2. Methods Allergic inflammation was induced in BALBc mice by intranasal exposure to HDM for 10 consecutive days. This model reproduces spontaneous exposure to aeroallergens by asthmatic patients. In order to impair, but not fully block, COX-2 production in the airways, some of the animals received an intranasal antisense oligonucleotide. Lung COX-2 expression and activity were measured along with bronchovascular inflammation, airway reactivity, and prostaglandin production. Results We observed impaired COX-2 mRNA and protein expression in the lung tissue of selective oligonucleotide-treated sensitized mice. This was accompanied by diminished production of mPGE synthase and PGE2 in the airways. In sensitized mice, the oligonucleotide induced increased airway hyperreactivity (AHR to methacholine, but a substantially reduced bronchovascular inflammation. Finally, mRNA levels of hPGD synthase remained unchanged. Conclusion Intranasal antisense therapy against COX-2 in vivo mimicked the reported impairment of COX-2 regulation in the airway cells of asthmatic patients. This strategy revealed an unexpected novel dual effect: inflammation was improved but AHR worsened. This approach will provide insights into the differential regulation of inflammation and lung function in asthma, and will help identify pharmacological targets within the COX-2/PG system.

  2. Modulation of the vagal bradycardia evoked by stimulation of upper airway receptors by central 5-HT1 receptors in anaesthetized rabbits

    Science.gov (United States)

    Dando, Simon B; Skinner, Matthew R; Jordan, David; Ramage, Andrew G

    1998-01-01

    The effects of central application of 5-HT1A and 5-HT1B/1D receptor ligands on the reflex bradycardia, apnoea, renal sympathoexcitation and pressor response evoked by stimulating upper airway receptors with smoke in atenolol-pretreated anaesthetized rabbits were studied.Intracisternal administration of the 5-HT1A receptor antagonists WAY-100635 (100 μg kg−1) and (−)pindolol (100 μg kg−1) significantly reduced the smoke-induced bradycardia, attenuated the pressor response and in the case of (−)pindolol, sympathetic nerve activity. The same dose of WAY-100635 i.v. was without effect.Buspirone (200 μg kg−1, i.c.) potentiated the reflex bradycardia. This action was prevented if the animals were pretreated with WAY-100635 (100 μg kg−1, i.v.)(+)8-OH-DPAT (25 μg kg−1, i.c.) attenuated the evoked bradycardia, pressor response, apnoea and renal sympathoexcitation. The attenuation of the apnoea and renal sympathoexcitation, but not the bradycardia or pressor response was prevented in animals pretreated with WAY-100635 (100 μg kg−1, i.v.). The attenuation of the reflex bradycardia and the reduction in the renal sympathoexcitation were reduced by pretreatment with the 5-HT1B/1D receptor antagonist GR127935 (100 μg kg−1, i.v.).In WAY-100635 (100 μg kg−1, i.v.) pretreated animals, sumatriptan (a 5-HT1B/1D receptor agonist) reduced the reflex bradycardia and the pressor response. The 5-HT1B/1D receptor antagonist GR127935 (20 μg kg−1, i.c. or 100 μg kg−1, i.v.) had no effect on the reflex responses.In conclusion, the present data are consistent with the hypothesis that activation of central 5-HT1A receptors potentiate whilst activation of 5-HT1B/1D receptors attenuate the reflex activation of cardiac preganglionic vagal motoneurones evoked by stimulation of upper airway receptors with smoke in rabbits. PMID:9786516

  3. The ΔF508-CFTR mutation inhibits wild-type CFTR processing and function when co-expressed in human airway epithelia and in mouse nasal mucosa

    Directory of Open Access Journals (Sweden)

    Tucker Torry A

    2012-09-01

    Full Text Available Abstract Background Rescue or correction of CFTR function in native epithelia is the ultimate goal of CF therapeutics development. Wild-type (WT CFTR introduction and replacement is also of particular interest. Such therapies may be complicated by possible CFTR self-assembly into an oligomer or multimer. Results Surprisingly, functional CFTR assays in native airway epithelia showed that the most common CFTR mutant, ΔF508-CFTR (ΔF-CFTR, inhibits WT-CFTR when both forms are co-expressed. To examine more mechanistically, both forms of CFTR were transfected transiently in varying amounts into IB3-1 CF human airway epithelial cells and HEK-293 human embryonic kidney cells null for endogenous CFTR protein expression. Increasing amounts of ΔF-CFTR inhibited WT-CFTR protein processing and function in CF human airway epithelial cells but not in heterologous HEK-293 cells. Stably expressed ΔF-CFTR in clones of the non-CF human airway epithelial cell line, CALU-3, also showed reduction in cAMP-stimulated anion secretion and in WT-CFTR processing. An ultimate test of this dominant negative-like effect of ΔF-CFTR on WT-CFTR was the parallel study of two different CF mouse models: the ΔF-CFTR mouse and the bitransgenic CFTR mouse corrected in the gut but null in the lung and airways. WT/ΔF heterozygotes had an intermediate phenotype with regard to CFTR agonist responses in in vivo nasal potential difference (NPD recordings and in Ussing chamber recordings of short-circuit current (ISC in vitro on primary tracheal epithelial cells isolated from the same mice. In contrast, CFTR bitransgenic +/− heterozygotes had no difference in their responses versus +/+ wild-type mice. Conclusions Taken altogether, these data suggest that ΔF-CFTR and WT-CFTR co-assemble into an oligomeric macromolecular complex in native epithelia and share protein processing machinery and regulation at the level of the endoplasmic reticulum (ER. As a consequence, ΔF-CFTR slows WT

  4. Nodal centrality of functional network in the differentiation of schizophrenia.

    Science.gov (United States)

    Cheng, Hu; Newman, Sharlene; Goñi, Joaquín; Kent, Jerillyn S; Howell, Josselyn; Bolbecker, Amanda; Puce, Aina; O'Donnell, Brian F; Hetrick, William P

    2015-10-01

    A disturbance in the integration of information during mental processing has been implicated in schizophrenia, possibly due to faulty communication within and between brain regions. Graph theoretic measures allow quantification of functional brain networks. Functional networks are derived from correlations between time courses of brain regions. Group differences between SZ and control groups have been reported for functional network properties, but the potential of such measures to classify individual cases has been little explored. We tested whether the network measure of betweenness centrality could classify persons with schizophrenia and normal controls. Functional networks were constructed for 19 schizophrenic patients and 29 non-psychiatric controls based on resting state functional MRI scans. The betweenness centrality of each node, or fraction of shortest-paths that pass through it, was calculated in order to characterize the centrality of the different regions. The nodes with high betweenness centrality agreed well with hub nodes reported in previous studies of structural and functional networks. Using a linear support vector machine algorithm, the schizophrenia group was differentiated from non-psychiatric controls using the ten nodes with the highest betweenness centrality. The classification accuracy was around 80%, and stable against connectivity thresholding. Better performance was achieved when using the ranks as feature space as opposed to the actual values of betweenness centrality. Overall, our findings suggest that changes in functional hubs are associated with schizophrenia, reflecting a variation of the underlying functional network and neuronal communications. In addition, a specific network property, betweenness centrality, can classify persons with SZ with a high level of accuracy.

  5. Application of bronchoscopy in etiological diagnosis of central airway obstruction%支气管镜在中央气道阻塞性病变的病因诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    陈为忠; 谢伟见; 付敏; 曹惠红

    2012-01-01

    cases there were male 30 cases,female 12 cases,aged 19-81 years old,the median age 56 years,12 cases of bronchial squamous cell carcinoma (12/42),6 cases of adenocarcinoma (6/42),10 cases of small cell lung cancer (10/42),4 cases of tracheal or endobronchial tuberculosis in (4/42),4 cases of chronic inflammation induced mucus phlegm bolts (4/42),2 cases of esophageal squamous cell carcinoma (2/42),1 case of foreign body (1/42),2 cases of bronchial calculus (2/42),1 case of pulmonary cyst and bleeding package (1/42).There were 38 cases of cough in the 42 patients,16 cases of hemoptysis,14 cases of shortness of breath or difficult breathing,8 cases of chest pain.All patients were underwent chest CT including 18 patients with a routine three-dimensional reconstruction of the airway,40 cases were found direct lesions or indirect signs of lesions.All patients were underwent bronchoscopy.Lesions or suspicious lesions were found.There were 34 cases with airway organic disease.Biopsy forceps were used to obtain tissue samples with the initial pathological positive rate 100%.Pulmonary function were checked in 38 patients.26 of them had obstructive or mixed ventilatory dysfunction,6 cases had flow-volume loop platform.Conclusions Central airway obstructive diseases have complex causes which mainly were malignant lesions.Its common symptoms are cough,dyspnea,hemoptysis,chest pain,weight loss,fatigue,or no specific performance.By chest CT scan jointed airway remodeling,obstructive pneumonia,obstructive atelectasis,obstructive emphysema could be mainly observed.Brochoscopy and biopsy provide accurate information for diagnosis,and have irreplaceable value for pathogenesis diagnosis.Different treatment should be chosen according to different causes and different pathological changes.

  6. The Lung Microbiome and Airway Disease.

    Science.gov (United States)

    Lynch, Susan V

    2016-12-01

    A growing body of literature has demonstrated relationships between the composition of the airway microbiota (mixed-species communities of microbes that exist in the respiratory tract) and critical features of immune response and pulmonary function. These studies provide evidence that airway inflammatory status and capacity for repair are coassociated with specific taxonomic features of the airway microbiome. Although directionality has yet to be established, the fact that microbes are known drivers of inflammation and tissue damage suggests that in the context of chronic inflammatory airway disease, the composition and, more importantly, the function, of the pulmonary microbiome represent critical factors in defining airway disease outcomes.

  7. Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons.

    OpenAIRE

    Jacoby, D B; Xiao, H Q; Lee, N. H.; Chan-Li, Y; Fryer, A. D.

    1998-01-01

    Viral infections increase vagally mediated reflex bronchoconstriction. Decreased function of inhibitory M2 muscarinic receptors on the parasympathetic nerve endings is likely to contribute to increased acetylcholine release. In this study, we used cultured airway parasympathetic neurons to determine the effects of parainfluenza virus and of interferon (IFN)-gamma on acetylcholine release, inhibitory M2 receptor function, and M2 receptor gene expression. In control cultures, electrically stimu...

  8. Compensatory recombination phenomena of neurological functions in central dysphagia patients

    Directory of Open Access Journals (Sweden)

    Xiao-dong Yuan

    2015-01-01

    Full Text Available We speculate that cortical reactions evoked by swallowing activity may be abnormal in patients with central infarction with dysphagia. The present study aimed to detect functional imaging features of cerebral cortex in central dysphagia patients by using blood oxygen level-dependent functional magnetic resonance imaging techniques. The results showed that when normal controls swallowed, primary motor cortex (BA4, insula (BA13, premotor cortex (BA6/8, supramarginal gyrus (BA40, and anterior cingulate cortex (BA24/32 were activated, and that the size of the activated areas were larger in the left hemisphere compared with the right. In recurrent cerebral infarction patients with central dysphagia, BA4, BA13, BA40 and BA6/8 areas were activated, while the degree of activation in BA24/32 was decreased. Additionally, more areas were activated, including posterior cingulate cortex (BA23/31, visual association cortex (BA18/19, primary auditory cortex (BA41 and parahippocampal cortex (BA36. Somatosensory association cortex (BA7 and left cerebellum in patients with recurrent cerebral infarction with central dysphagia were also activated. Experimental findings suggest that the cerebral cortex has obvious hemisphere lateralization in response to swallowing, and patients with recurrent cerebral infarction with central dysphagia show compensatory recombination phenomena of neurological functions. In rehabilitative treatment, using the favorite food of patients can stimulate swallowing through visual, auditory, and other nerve conduction pathways, thus promoting compensatory recombination of the central cortex functions.

  9. Compensatory recombination phenomena of neurological functions in central dysphagia patients

    Institute of Scientific and Technical Information of China (English)

    Xiao-dong Yuan; Li-fu Zhou; Shu-juan Wang; Yan-sheng Zhao; Xiao-jie Wang; Li-li Zhang; Shou-hong Wang; Ya-jie Zhang; Li Chen

    2015-01-01

    We speculate that cortical reactions evoked by swallowing activity may be abnormal in patients with central infarction with dysphagia. The present study aimed to detect functional imaging features of cerebral cortex in central dysphagia patients by using blood oxygen level-depen-dent functional magnetic resonance imaging techniques. The results showed that when normal controls swallowed, primary motor cortex (BA4), insula (BA13), premotor cortex (BA6/8), supramarginal gyrus (BA40), and anterior cingulate cortex (BA24/32) were activated, and that the size of the activated areas were larger in the left hemisphere compared with the right. In re-current cerebral infarction patients with central dysphagia, BA4, BA13, BA40 and BA6/8 areas were activated, while the degree of activation in BA24/32 was decreased. Additionally, more areas were activated, including posterior cingulate cortex (BA23/31), visual association cortex (BA18/19), primary auditory cortex (BA41) and parahippocampal cortex (BA36). Somatosen-sory association cortex (BA7) and left cerebellum in patients with recurrent cerebral infarction with central dysphagia were also activated. Experimental ifndings suggest that the cerebral cortex has obvious hemisphere lateralization in response to swallowing, and patients with recurrent cerebral infarction with central dysphagia show compensatory recombination phenomena of neurological functions. In rehabilitative treatment, using the favorite food of patients can stimu-late swallowing through visual, auditory, and other nerve conduction pathways, thus promoting compensatory recombination of the central cortex functions.

  10. Central serotonergic and noradrenergic receptors in functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    S O'Mahony; TG Dinan; PW Keeling; ASB Chua

    2006-01-01

    Functional dyspepsia is a symptom complex characterised by upper abdominal discomfort or pain, early satiety,motor abnormalities, abdominal bloating and nausea in the absence of organic disease. The central nervous system plays an important role in the conducting and processing of visceral signals. Alterations in brain processing of pain, perception and affective responses may be key factors in the pathogenesis of functional dyspepsia. Central serotonergic and noradrenergic receptor systems are involved in the processing of motor,sensory and secretory activities of the gastrointestinal tract. Visceral hypersensitivity is currently regarded as the mechanism responsible for both motor alterations and abdominal pain in functional dyspepsia. Some studies suggest that there are alterations in central serotonergic and noradrenergic systems which may partially explain some of the symptoms of functional dyspepsia. Alterations in the autonomic nervous system may be implicated in the motor abnormalities and increases in visceral sensitivity in these patients.Noradrenaline is the main neurotransmitter in the sympathetic nervous system and again alterations in the functioning of this system may lead to changes in motor function. Functional dyspepsia causes considerable burden on the patient and society. The pathophysiology of functional dyspepsia is not fully understood but alterations in central processing by the serotonergic and noradrenergic systems may provide plausible explanations for at least some of the symptoms and offer possible treatment targets for the future.

  11. Airway vascular reactivity and vascularisation in human chronic airway disease

    NARCIS (Netherlands)

    Bailey, Simon R; Boustany, Sarah; Burgess, Janette K; Hirst, Stuart J; Sharma, Hari S; Simcock, David E; Suravaram, Padmini R; Weckmann, Markus

    2009-01-01

    Altered bronchial vascular reactivity and remodelling including angiogenesis are documented features of asthma and other chronic inflammatory airway diseases. Expansion of the bronchial vasculature under these conditions involves both functional (vasodilation, hyperperfusion, increased microvascular

  12. Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration.

    Science.gov (United States)

    Bentley, J Kelley; Hershenson, Marc B

    2008-01-01

    Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known. This review will consider the evidence for airway smooth muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.

  13. The impulse influence function for de-centralized control

    Institute of Scientific and Technical Information of China (English)

    ZHONG Wanxie

    2004-01-01

    Impulse influence matrix function is introduced based on that the de-centralized control analysis is analogous to the sub-structural analysis in structural mechanics. The static sub-structural analysis is analogous to the usual de-centralized control, whereas the dynamic sub-structural analysis corresponds to the de-centralized control theory. The reciprocal symmetry for the impulse influence matrix function is proved, and is solved by the precise integration method for time invariant system, giving the results up to computer precision. Based on the impulse influence functions of subsystems, the combination of subsystems can lead to a set of integral equations and be solved numerically. Numerical example demonstrates the effectiveness of the method.

  14. Functional evidence of persistent airway obstruction in rats following a two-hour inhalation exposure to methyl isocyanate

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, M.A.; Fitzgerald, S.; Menache, M.G.; Costa, D.L.; Bucher, J.R.

    1987-06-01

    Pulmonary function was assessed in male, F344 rats 1,2,4,7 and 13 weeks after a single 2-hr exposure to 0, 3, 10, or 30 ppm methyl isocyanate. No significant changes were observed in the rats exposed to 3 ppm through 13 weeks. Diffusing capacity (DL/sub co/), quasistatic lung compliance, and homogeneity of ventilation, as determined by multibreath nitrogen washout, were depressed in the rats exposed to 10 and 30 ppm by 1 week after exposure. None of the rats exposed to 30 ppm survived beyond 1 week. By 13 weeks, dramatic increases in lung volumes were observed in the rats exposed to 10 ppm, while DL/sub co/ and lung compliance were only mildly affected. However, volume-specific DL/sub co/ and compliance were depressed in the rats exposed to 10 ppm, suggesting that lung hyperinflation or other compensatory means of increasing lung size occurred in response to the methyl isocyanate-induced lung lesion. This group also exhibited increased expiratory times during tidal breathing and severely impaired distribution of ventilated air. Collectively, these results suggest the development and likely progression of a severe, obstructive airway lesion with associated gas trapping, and the existence of a pronounced concentration-response relationship between 3 and 10 ppm methyl isocyanate exposures.

  15. Effects of 12 months continuous positive airway pressure on sympathetic activity related brainstem function and structure in obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Luke Anthony Henderson

    2016-03-01

    Full Text Available Muscle sympathetic nerve activity (MSNA is greatly elevated in patients with obstructive sleep apnoea (OSA during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 subjects with OSA prior to and following 6 and 12 months of continuous positive airway pressure (CPAP treatment. We found that 6 and 12 months of CPAP treatment significantly reduced the elevated resting MSNA in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MNSA likely due to its effects on restoring brainstem structure and function.

  16. Airway smooth muscle dynamics : a common pathway of airway obstruction in asthma

    NARCIS (Netherlands)

    An, S S; Bai, T R; Bates, J H T; Black, J L; Brown, R H; Brusasco, V; Chitano, P; Deng, L; Dowell, M; Eidelman, D H; Fabry, B; Fairbank, N J; Ford, L E; Fredberg, J J; Gerthoffer, W T; Gilbert, S H; Gosens, R; Gunst, S J; Halayko, A J; Ingram, R H; Irvin, C G; James, A L; Janssen, L J; King, G G; Knight, D A; Lauzon, A M; Lakser, O J; Ludwig, M S; Lutchen, K R; Maksym, G N; Martin, J G; Mauad, T; McParland, B E; Mijailovich, S M; Mitchell, H W; Mitchell, R W; Mitzner, W; Murphy, T M; Paré, P D; Pellegrino, R; Sanderson, M J; Schellenberg, R R; Seow, C Y; Silveira, P S P; Smith, P G; Solway, J; Stephens, N L; Sterk, P J; Stewart, A G; Tang, D D; Tepper, R S; Tran, T; Wang, L

    2007-01-01

    Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series o

  17. Dietary intake, lung function and airway inflammation in Mexico City school children exposed to air pollutants

    Directory of Open Access Journals (Sweden)

    Díaz-Sánchez David

    2009-12-01

    Full Text Available Abstract Introduction Air pollutant exposure has been associated with an increase in inflammatory markers and a decline in lung function in asthmatic children. Several studies suggest that dietary intake of fruits and vegetables might modify the adverse effect of air pollutants. Methods A total of 158 asthmatic children recruited at the Children's Hospital of Mexico and 50 non-asthmatic children were followed for 22 weeks. Pulmonary function was measured and nasal lavage collected and analyzed every 2 weeks. Dietary intake was evaluated using a 108-item food frequency questionnaire and a fruit and vegetable index (FVI and a Mediterranean diet index (MDI were constructed. The impact of these indices on lung function and interleukin-8 (IL-8 and their interaction with air pollutants were determined using mixed regression models with random intercept and random slope. Results FVI was inversely related to IL-8 levels in nasal lavage (p 1 (test for trend p 1 and FVC as was with MDI and ozone for FVC. No effect of diet was observed among healthy children. Conclusion Our results suggest that fruit and vegetable intake and close adherence to the Mediterranean diet have a beneficial effect on inflammatory response and lung function in asthmatic children living in Mexico City.

  18. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    Full Text Available BACKGROUND: The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. CONCLUSION/SIGNIFICANCE: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of

  19. Inspiratory high frequency airway oscillation attenuates resistive loaded dyspnea and modulates respiratory function in young healthy individuals.

    Science.gov (United States)

    Morris, Theresa; Sumners, David Paul; Green, David Andrew

    2014-01-01

    Direct chest-wall percussion can reduce breathlessness in Chronic Obstructive Pulmonary Disease and respiratory function may be improved, in health and disease, by respiratory muscle training (RMT). We tested whether high-frequency airway oscillation (HFAO), a novel form of airflow oscillation generation can modulate induced dyspnoea and respiratory strength and/or patterns following 5 weeks of HFAO training (n = 20) compared to a SHAM-RMT (conventional flow-resistive RMT) device (n = 15) in healthy volunteers (13 males; aged 20-36 yrs). HFAO causes oscillations with peak-to-peak amplitude of 1 cm H2O, whereas the SHAM-RMT device was identical but created no pressure oscillation. Respiratory function, dyspnoea and ventilation during 3 minutes of spontaneous resting ventilation, 1 minute of maximal voluntary hyperventilation and 1 minute breathing against a moderate inspiratory resistance, were compared PRE and POST 5-weeks of training (2 × 30 breaths at 70% peak flow, 5 days a week). Training significantly reduced NRS dyspnoea scores during resistive loaded ventilation, both in the HFAO (p = 0.003) and SHAM-RMT (p = 0.005) groups. Maximum inspiratory static pressure (cm H2O) was significantly increased by HFAO training (vs. PRE; pRMT (vs. PRE; p = 0.021) groups. Peak inspiratory flow rate (L.s(-1)) achieved during the maximum inspiratory dynamic pressure manoeuvre increased significantly POST (vs. PRE; p = 0.001) in the HFAO group only. HFAO reduced inspiratory resistive loading-induced dyspnoea and augments static and dynamic maximal respiratory manoeuvre performance in excess of flow-resistive IMT (SHAM-RMT) in healthy individuals without the respiratory discomfort associated with RMT.

  20. Inspiratory high frequency airway oscillation attenuates resistive loaded dyspnea and modulates respiratory function in young healthy individuals.

    Directory of Open Access Journals (Sweden)

    Theresa Morris

    Full Text Available Direct chest-wall percussion can reduce breathlessness in Chronic Obstructive Pulmonary Disease and respiratory function may be improved, in health and disease, by respiratory muscle training (RMT. We tested whether high-frequency airway oscillation (HFAO, a novel form of airflow oscillation generation can modulate induced dyspnoea and respiratory strength and/or patterns following 5 weeks of HFAO training (n = 20 compared to a SHAM-RMT (conventional flow-resistive RMT device (n = 15 in healthy volunteers (13 males; aged 20-36 yrs. HFAO causes oscillations with peak-to-peak amplitude of 1 cm H2O, whereas the SHAM-RMT device was identical but created no pressure oscillation. Respiratory function, dyspnoea and ventilation during 3 minutes of spontaneous resting ventilation, 1 minute of maximal voluntary hyperventilation and 1 minute breathing against a moderate inspiratory resistance, were compared PRE and POST 5-weeks of training (2 × 30 breaths at 70% peak flow, 5 days a week. Training significantly reduced NRS dyspnoea scores during resistive loaded ventilation, both in the HFAO (p = 0.003 and SHAM-RMT (p = 0.005 groups. Maximum inspiratory static pressure (cm H2O was significantly increased by HFAO training (vs. PRE; p<0.001. Maximum inspiratory dynamic pressure was increased by training in both the HFAO (vs. PRE; p<0.001 and SHAM-RMT (vs. PRE; p = 0.021 groups. Peak inspiratory flow rate (L.s(-1 achieved during the maximum inspiratory dynamic pressure manoeuvre increased significantly POST (vs. PRE; p = 0.001 in the HFAO group only. HFAO reduced inspiratory resistive loading-induced dyspnoea and augments static and dynamic maximal respiratory manoeuvre performance in excess of flow-resistive IMT (SHAM-RMT in healthy individuals without the respiratory discomfort associated with RMT.

  1. Sarcoidosis of the upper and lower airways.

    Science.gov (United States)

    Morgenthau, Adam S; Teirstein, Alvin S

    2011-12-01

    Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed.

  2. Overexpression of mclca3 in airway epithelium of asthmatic murine models with airway inflammation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui-lan; HE Li

    2010-01-01

    Asthma is a worldwide prevalent disease that is a considerable health burden in many countries.1 In recent years, the airway epithelium is increasingly recognized as a central contributor to the pathogenesis of asthma.2 One of the most highly induced genes in epithelial cells in experimental allergic airway disease is the third murine calcium-activated chloride channel homologue (mclca3, alias gob-5). Its human homology protein is hCLCA1,3,4 which has been identified as clinically relevant molecules in diseases with secretory dysfunctions including asthma and cystic fibrosis. In initial studies, mclca3 was thought to be a member of calcium-activated chloride channel (CaCCs) family,whereas some new interesting reports suggest that the two mclca3 cleavage products cannot form an anion channel on their own but may instead act as extracellular signaling molecules with as yet unknown functions and interacting partners.5

  3. Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

    Directory of Open Access Journals (Sweden)

    Nava Pat

    2011-03-01

    Full Text Available Abstract Background Is Impulse Oscillometry System (IOS a valuable tool to measure respiratory system function in Children? Asthma (A is the most prevalent chronic respiratory disease in children. Therefore, early and accurate assessment of respiratory function is of tremendous clinical interest in diagnosis, monitoring and treatment of respiratory conditions in this subpopulation. IOS has been successfully used to measure lung function in children with a high degree of sensitivity and specificity to small airway impairments (SAI and asthma. IOS measures of airway function and equivalent electrical circuit models of the human respiratory system have been developed to quantify the severity of these conditions. Previously, we have evaluated several known respiratory models based on the Mead's model and more parsimonious versions based on fitting IOS data known as extended RIC (eRIC and augmented RIC (aRIC models have emerged, which offer advantages over earlier models. Methods IOS data from twenty-six children were collected and compared during pre-bronchodilation (pre-B and post- bronchodilation (post-B conditions over a period of 2 years. Results and Discussion Are the IOS and model parameters capable of differentiating between healthy children and children with respiratory system distress? Children were classified into two main categories: Healthy (H and Small Airway-Impaired (SAI. The IOS measures and respiratory model parameters analyzed differed consistently between H and SAI children. SAI children showed smaller trend of "growth" and larger trend of bronchodilator responses than H children. The two model parameters: peripheral compliance (Cp and peripheral resistance (Rp tracked IOS indices of small airway function well. Cp was a more sensitive index than Rp. Both eRIC and aRIC Cps and the IOS Reactance Area, AX, (also known as the "Goldman Triangle" showed good correlations. Conclusions What are the most useful IOS and model parameters? In

  4. Functional requirements for a central research imaging data repository.

    Science.gov (United States)

    Franke, Thomas; Gruetz, Romanus; Dickmann, Frank

    2013-01-01

    The current situation at many university medical centers regarding the management of biomedical research imaging data leaves much to be desired. In contrast to the recommendations of the German Research Foundation (DFG) and the German Council of Sciences and Humanities regarding the professional management of research data, there are commonly many individual data pools for research data in each institute and the management remains the responsibility of the researcher. A possible solution for this situation would be to install local central repositories for biomedical research imaging data. In this paper, we developed a scenario based on abstracted use-cases for institutional research undertakings as well as collaborative biomedical research projects and analyzed the functional requirements that a local repository would have to fulfill. We determined eight generic categories of functional requirements, which can be viewed as a basic guideline for the minimum functionality of a central repository for biomedical research imaging data.

  5. Pneumocystis colonization, airway inflammation, and pulmonary function decline in acquired immunodeficiency syndrome.

    Science.gov (United States)

    Norris, Karen A; Morris, Alison; Patil, Sangita; Fernandes, Eustace

    2006-01-01

    As a result of improved diagnosis, treatment, and supportive care for HIV-infected patients, AIDS in developed countries has now become a chronic infection with prolonged survival time, but longterm complications are increasing contributors to morbidity and mortality. HIV-infected patients are at increased risk for the development of pulmonary complications, including chronic obstructive pulmonary disease (COPD); however, the mechanisms associated with this increased susceptibility have not been defined. Infectious agents may contribute to the development of COPD by upregulating inflammatory mediators in the lung that act in concert with cigarette smoke to promote lung pathology. Studies in human subjects and non-human primate models of AIDS suggest that the inflammatory response to asymptomatic carriage or colonization by the opportunistic pathogen, Pneumocystis sp. (Pc), is similar to that of COPD, which is characterized by influx of CD8+ T cells, neutrophils, and macrophages into the lungs. We have shown a high frequency of Pc colonization among asymptomatic HIV-infected subjects and in non-HIV infected subjects with COPD. To investigate the role of Pc in the progression of obstructive lung disease in HIV infections, we developed a non-human primate model of Pc colonizatoin and infection in simian immunodeficiency virus (SIV)-infected macaques. These animals develop a prolonged colonization state characterized by a persistent influx of CD8+ T cells and neutrophils, and local increases in IL-8, IFN-gamma, and TNF-alpha. SIV-infected Pc-colonized monkeys show progressive decline in pulmonary function compared to SIV-infected monkeys. We hypothesize that in the context of AIDS-immune dysfunction, Pc colonization induces inflammatory responses leading to changes in pulmonary function and architecture similar to that seen in emphysema. Information gained from these studies will lead to the development of interventions to prevent lung injury associated with Pc

  6. Structural and functional features of central nervous system lymphatic vessels.

    Science.gov (United States)

    Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

  7. Airway remodeling in asthma: what really matters.

    Science.gov (United States)

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael

    2017-03-01

    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  8. Novel non-canonical TGF-beta signaling networks : Emerging roles in airway smooth muscle phenotype and function

    NARCIS (Netherlands)

    Yeganeh, Behzad; Mukherjee, Subhendu; Moir, Lyn M.; Kumawat, Kuldeep; Kashani, Hessam H.; Bagchi, Rushita A.; Baarsma, Hoeke A.; Gosens, Reinoud; Ghavami, Saeid

    2013-01-01

    The airway smooth muscle (ASM) plays an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD). ASM cells express a wide range of receptors involved in contraction, growth, matrix protein production and the secretion of cytokines and chemokines. Transforming

  9. Glutathione and airway function

    NARCIS (Netherlands)

    Kloek, Joris

    2001-01-01

    De pathologie van astma wordt onder meer gekenmerkt door luchtwegvernauwing en een ontsteking in de longen. De samenhang tussen deze kenmerken is nog slecht begrepen. Een van de gevolgen van de eerder genoemde ontsteking is dat afweercellen in de longen zgn. reactieve zuursofvormen produceren en afs

  10. Role of cholecystokinin and central serotonergic receptors in functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    Andrew Seng Boon Chua; PWN Keeling; TG Dinan

    2006-01-01

    Symptoms of functional dyspepsia are characterized by upper abdominal discomfort or pain, early satiety, postprandial fullness, bloating, nausea and vomiting. It is a chronic disorder, with symptoms more than 3 mo per year, and no evidence of organic diseases. Dysfunctional motility, altered visceral sensation, and psychosocial factors have all been identified as major pathophysiological mechanisms. It is believed that these pathophysiological mechanisms interact to produce the observed symptoms.Dyspepsia has been categorized into three subgroups based on dominant symptoms. Dysmotility-like dyspepsia describes a subgroup of patients whose symptom complex is usually related to a gastric sensorimotor dysfunction. The brain-gut peptide cholecystokinin (CCK)and serotonin (5-HT) share certain physiological effects.Both have been shown to decrease gastric emptying and affect satiety. Furthermore the CCK induced anorexia depended on serotonergic functions probably acting via central pathways. We believe that abnormalities of central serotonergic receptors functioning together with a hyper responsiveness to CCK or their interactions may be responsible for the genesis of symptoms in functional dyspepsia (FD).

  11. Importance of slow vital capacity in the detection of airway obstruction

    Directory of Open Access Journals (Sweden)

    Ana Raquel Goncalves de Barros

    2013-06-01

    Full Text Available OBJECTIVE: To investigate the presence of airway obstruction by determining the FEV1/FVC and FEV1/slow vital capacity (SVC ratios. METHODS: This was a quantitative, retrospective cross-sectional study. The sample comprised 1,084 individuals who underwent spirometry and plethysmography in a central hospital in Lisbon, Portugal. The study sample was stratified into six groups, by pulmonary function. RESULTS: The analysis of the FEV1/FVC ratio revealed the presence of airway obstruction in 476 individuals (43.9%, compared with 566 individuals (52.2% for the analysis of the FEV1/SVC ratio. In the airway obstruction, airway obstruction plus lung hyperinflation, and mixed pattern groups, the difference between SVC and FVC (SVC − FVC was statistically superior to that in the normal pulmonary function, reduced FEF, and restrictive lung disease groups. The SVC − FVC parameter showed a significant negative correlation with FEV1 (in % of the predicted value only in the airway obstruction plus lung hyperinflation group. CONCLUSIONS: The FEV1/SVC ratio detected the presence of airway obstruction in more individuals than did the FEV1/FVC ratio; that is, the FEV1/SVC ratio is more reliable than is the FEV1/FVC ratio in the detection of obstructive pulmonary disease.

  12. Airway management in trauma

    Directory of Open Access Journals (Sweden)

    Rashid M Khan

    2011-01-01

    Full Text Available Trauma has assumed epidemic proportion. 10% of global road accident deaths occur in India. Hypoxia and airway mismanagement are known to contribute up to 34% of pre-hospital deaths in these patients. A high degree of suspicion for actual or impending airway obstruction should be assumed in all trauma patients. Objective signs of airway compromise include agitation, obtundation, cyanosis, abnormal breath sound and deviated trachea. If time permits, one should carry out a brief airway assessment prior to undertaking definitive airway management in these patients. Simple techniques for establishing and maintaining airway patency include jaw thrust maneuver and/or use of oro- and nas-opharyngeal airways. All attempts must be made to perform definitive airway management whenever airway is compromised that is not amenable to simple strategies. The selection of airway device and route- oral or -nasal, for tracheal intubation should be based on nature of patient injury, experience and skill level.

  13. Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells?

    Directory of Open Access Journals (Sweden)

    Yvonne Nussbaumer-Ochsner

    Full Text Available Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath.Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test, measurement of fractional exhaled nitric oxide (FeNO and pH/8-isoprostane in exhaled breath condensate (EBC. Lung tissue sections containing cancer-free large (LA and small airways (SA were stained for inflammatory cells. Mucosal (MCT respectively connective tissue mast cells (MCTC and interleukin-17A (IL-17A expression by mast cells was analysed using a double-staining protocol.The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MCT were higher in the lamina propria of SA compared to LA (MCTC: 49 vs. 27.4 cells/mm2; MCT: 162.5 vs. 35.4 cells/mm2; P<0.005 for both instances. IL-17A expression was predominantly detected in MCTC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (rs= -0.39, for the FEV1% pred. (rs= 0.37 and for FEV1/FVC ratio (rs=0.38 with MCT in SA (P<0.05 for all instances. 8-isoprostane concentration correlated with the mast cells in the SA (rs=0.44, there was no correlation for pH or FeNO with cellular distribution in SA.Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the

  14. Airway Tree Extraction with Locally Optimal Paths

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Sporring, Jon; Pedersen, Jesper Johannes Holst

    2009-01-01

    This paper proposes a method to extract the airway tree from CT images by continually extending the tree with locally optimal paths. This is in contrast to commonly used region growing based approaches that only search the space of the immediate neighbors. The result is a much more robust method...... for tree extraction that can overcome local occlusions. The cost function for obtaining the optimal paths takes into account of an airway probability map as well as measures of airway shape and orientation derived from multi-scale Hessian eigen analysis on the airway probability. Significant improvements...

  15. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  16. Differential expression and function of breast regression protein 39 (BRP-39 in murine models of subacute cigarette smoke exposure and allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Coyle Anthony J

    2011-04-01

    Full Text Available Abstract Background While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM, is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation. Methods CD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation. Results Cigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke. Conclusions These data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1

  17. Relativistic central--field Green's functions for the RATIP package

    CERN Document Server

    Koval, P; Koval, Peter; Fritzsche, Stephan

    2004-01-01

    From perturbation theory, Green's functions are known for providing a simple and convenient access to the (complete) spectrum of atoms and ions. Having these functions available, they may help carry out perturbation expansions to any order beyond the first one. For most realistic potentials, however, the Green's functions need to be calculated numerically since an analytic form is known only for free electrons or for their motion in a pure Coulomb field. Therefore, in order to facilitate the use of Green's functions also for atoms and ions other than the hydrogen--like ions, here we provide an extension to the Ratip program which supports the computation of relativistic (one--electron) Green's functions in an -- arbitrarily given -- central--field potential $\\rV(r)$. Different computational modes have been implemented to define these effective potentials and to generate the radial Green's functions for all bound--state energies $E < 0$. In addition, care has been taken to provide a user--friendly component...

  18. Affect integration and reflective function: clarification of central conceptual issues.

    Science.gov (United States)

    Solbakken, Ole André; Hansen, Roger Sandvik; Monsen, Jon Trygve

    2011-07-01

    The importance of affect regulation, modulation or integration for higher-order reflection and adequate functioning is increasingly emphasized across different therapeutic approaches and theories of change. These processes are probably central to any psychotherapeutic endeavor, whether explicitly conceptualized or not, and in recent years a number of therapeutic approaches have been developed that explicitly target them as a primary area of change. However, there still is important lack of clarity in the field regarding the understanding and operationalization of affect integration, particularly when it comes to specifying underlying mechanisms, the significance of different affect states, and the establishment of operational criteria for measurement. The conceptual relationship between affect integration and reflective function thus remains ambiguous. The present article addresses these topics, indicating ways in which a more complex and exhaustive understanding of integration of affect, cognition and behavior can be attained.

  19. Non-invasive ventilation used as an adjunct to airway clearance treatments improves lung function during an acute exacerbation of cystic fibrosis: a randomised trial

    Directory of Open Access Journals (Sweden)

    Tiffany J Dwyer

    2015-07-01

    Full Text Available Question: During an acute exacerbation of cystic fibrosis, is non-invasive ventilation beneficial as an adjunct to the airway clearance regimen? Design: Randomised controlled trial with concealed allocation and intention-to-treat analysis. Participants: Forty adults with moderate to severe cystic fibrosis lung disease and who were admitted to hospital for an acute exacerbation. Intervention: Comprehensive inpatient care (control group compared to the same care with the addition of non-invasive ventilation during airway clearance treatments from Day 2 of admission until discharge (experimental group. Outcome measures: Lung function and subjective symptom severity were measured daily. Fatigue was measured at admission and discharge on the Schwartz Fatigue Scale from 7 (no fatigue to 63 (worst fatigue points. Quality of life and exercise capacity were also measured at admission and discharge. Length of admission and time to next hospital admission were recorded. Results: Analysed as the primary outcome, the experimental group had a greater rate of improvement in forced expiratory volume in 1 second (FEV1 than the control group, but this was not statistically significant (MD 0.13% predicted per day, 95% CI –0.03 to 0.28. However, the experimental group had a significantly higher FEV1 at discharge than the control group (MD 4.2% predicted, 95% CI 0.1 to 8.3. The experimental group reported significantly lower levels of fatigue on the Schwartz fatigue scale at discharge than the control group (MD 6 points, 95% CI 1 to 11. There was no significant difference between the experimental and control groups in subjective symptom severity, quality of life, exercise capacity, length of hospital admission or time to next hospital admission. Conclusion: Among people hospitalised for an acute exacerbation of cystic fibrosis, the use of non-invasive ventilation as an adjunct to the airway clearance regimen significantly improves FEV1 and fatigue. Trial

  20. Bronchoconstriction and airway biology : potential impact and therapeutic opportunities

    NARCIS (Netherlands)

    Gosens, Reinoud; Grainge, Chris

    2015-01-01

    Recent work has demonstrated that mechanical forces occurring in the airway as a consequence of bronchoconstriction are sufficient to not only induce symptoms but also influence airway biology. Animal and human in vitro and in vivo work demonstrates that the airways are structurally and functionally

  1. Exposure conditions, lung function and airway symptoms in industrial production of wood pellets. A pilot project; Exponeringsfoerhaallanden, lungfunktion och luftvaegsbesaer vid industriell produktion av traepellets. Ett pilotprojekt

    Energy Technology Data Exchange (ETDEWEB)

    Edman, Katja; Loefstedt, Haakan; Berg, Peter; Bryngelsson, I.L.; Fedeli, Cecilia; Selden, Anders [Oerebro Univ. Hospital (Sweden). Yrkes- och miljoemedicinska kliniken; Eriksson, Kaare [Umeaa Univ. Hospital (Sweden); Holmstroem, Mats; Rask- Andersen, Anna [Uppsala Univ. Hospital (Sweden)

    2002-02-01

    The production of wood pellets is a relatively new branch of the Swedish wood industry and has increased during the last years. A pilot study was performed to investigate the prevalence of airway symptoms, lung function and exposure among all 39 men employed in industrial production of wood pellets at six companies. The study included a questionnaire, medical examination, registration of nasal-PEF (peak expiratory flow) during a week, allergy screening (Phadiatop) and lung function (spirometry) before and after work shift. The results were compared with different reference data from other Swedish studies. Exposure measurements of monoterpenes and wood dust on filter and with a data logger (DataRAM) were also performed. The study group reported a higher frequency of cough without phlegm, awakening due to breathlessness and current asthma medication compared with reference data. For five of the six participants with physician-diagnosed asthma the disease debuted before the current employment and the results did not indicate an unusual asthma morbidity. Spirometry showed lower lung function before work shift than expected. However no difference over work shift was observed. A negative and non-significant correlation was seen between time with current work task and lung function. The study group reported a higher frequency of nasal symptoms mostly blockage, sneezing and dryness compared with reference data. The registrations of nasal-PEF did not show any differences between work and spare time. The prevalence of positive Phadiatop (23 %) did not differ from reference data. No association between exposure (wood dust and monoterpenes) and acute effects on lung function was observed. The wood dust exposure (0.16-19 mg/m{sup 3}) was high and 11 of 24 measurements exceeded the present Swedish occupational exposure limit of 2 mg/m{sup 3}. Peak exposures could be identified, e.g. at cleaning of engines with compressed air, with the DataRAM. The exposure to monoterpenes (0

  2. Implications of blast exposure for central auditory function: A review

    Directory of Open Access Journals (Sweden)

    Frederick J. Gallun, PhD

    2012-10-01

    Full Text Available Auditory system functions, from peripheral sensitivity to central processing capacities, are all at risk from a blast event. Accurate encoding of auditory patterns in time, frequency, and space are required for a clear understanding of speech and accurate localization of sound sources in environments with background noise, multiple sound sources, and/or reverberation. Further work is needed to refine the battery of clinical tests sensitive to the sorts of central auditory dysfunction observed in individuals with blast exposure. Treatment options include low-gain hearing aids, remote-microphone technology, and auditory-training regimens, but clinical evidence does not yet exist for recommending one or more of these options. As this population ages, the natural aging process and other potential brain injuries (such as stroke and blunt trauma may combine with blast-related brain changes to produce a population for which the current clinical diagnostic and treatment tools may prove inadequate. It is important to maintain an updated understanding of the scope of the issues present in this population and to continue to identify those solutions that can provide measurable improvements in the lives of Veterans who have been exposed to high-intensity blasts during the course of their military service.

  3. Functional roles of neuropeptides in the insect central nervous system

    Science.gov (United States)

    Nässel, D. R.

    With the completion of the Drosophila genome sequencing project we can begin to appreciate the extent of the complexity in the components involved in signal transfer and modulation in the nervous system of an animal with reasonably complex behavior. Of all the different classes of signaling substances utilized by the nervous system, the neuropeptides are the most diverse structurally and functionally. Thus peptidergic mechanisms of action in the central nervous system need to be analyzed in the context of the neuronal circuits in which they act and generalized traits cannot be established. By taking advantage of Drosophila molecular genetics and the presence of identifiable neurons, it has been possible to interfere with peptidergic signaling in small populations of central neurons and monitor the consequences on behavior. These studies and experiments on other insects with large identifiable neurons, permitting cellular analysis of signaling mechanisms, have outlined important principles for temporal and spatial action of neuropeptides in outputs of the circadian clock and in orchestrating molting behavior. Considering the large number of neuropeptides available in each insect species and their diverse distribution patterns, it is to be expected that different neuropeptides play roles in most aspects of insect physiology and behavior.

  4. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Wen Jing Sim

    2016-01-01

    Full Text Available Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.

  5. Central Andean crustal structure from receiver function analysis

    Science.gov (United States)

    Ryan, Jamie; Beck, Susan; Zandt, George; Wagner, Lara; Minaya, Estela; Tavera, Hernado

    2016-07-01

    The Central Andean Plateau (15°-27°S) is a high plateau in excess of 3 km elevation, associated with thickened crust along the western edge of the South America plate, in the convergent margin between the subducting Nazca plate and the Brazilian craton. We have calculated receiver functions using seismic data from a recent portable deployment of broadband seismometers in the Bolivian orocline (12°-21°S) region and combined them with waveforms from 38 other stations in the region to investigate crustal thickness and crust and mantle structures. Results from the receiver functions provide a more detailed map of crustal thickness than previously existed, and highlight mid-crustal features that match well with prior studies. The active volcanic arc and Altiplano have thick crust with Moho depths increasing from the central Altiplano (65 km) to the northern Altiplano (75 km). The Eastern Cordillera shows large along strike variations in crustal thickness. Along a densely sampled SW-NE profile through the Bolivian orocline there is a small region of thin crust beneath the high peaks of the Cordillera Real where the average elevations are near 4 km, and the Moho depth varies from 55 to 60 km, implying the crust is undercompensated by 5 km. In comparison, a broader region of high elevations in the Eastern Cordillera to the southeast near 20°S has a deeper Moho at 65-70 km and appears close to isostatic equilibrium at the Moho. Assuming the modern-day pattern of high precipitation on the flanks of the Andean plateau has existed since the late Miocene, we suggest that climate induced exhumation can explain some of the variations in present day crustal structure across the Bolivian orocline. We also suggest that south of the orocline at 20°S, the thicker and isostatically compensated crust is due to the absence of erosional exhumation and the occurrence of lithospheric delamination.

  6. Increase in markers of airway inflammation after ozone exposure can be observed also in stable treated asthmatics with minimal functional response to ozone

    Directory of Open Access Journals (Sweden)

    Dente Federico L

    2010-01-01

    Full Text Available Abstract Background The discrepancy between functional and inflammatory airway response to ozone has been reported in normal subjects, but few data are available for stable asthmatics regularly treated with inhaled corticosteroids. Methods Twenty-three well controlled, regularly treated, mild-to-moderate asthmatic patients underwent two sequential randomised exposures to either filtered air or ozone (0.3 ppm for 2 hours in a challenge chamber. Pulmonary function (PF was monitored, and patients with FEV1 decrease greater than 10% from pre-challenge value were considered as responders. Immediately after each exposure, exhaled breath condensate (EBC was collected to measure malondialdehyde (MDA. Six hours after each exposure, PF and EBC collection were repeated, and sputum was induced to measure inflammatory cell counts and soluble mediators (IL-8 and neutrophil elastase. The response to ozone was also evaluated according to the presence of polymorphism in oxidative stress related NQO1 and GSTM1 genes. Results After ozone exposure, sputum neutrophils significantly increased in responders (n = 8, but not in nonresponders (n = 15. Other markers of neutrophil activation in sputum supernatant and MDA in EBC significantly increased in all patients, but only in nonresponders the increase was significant. In nonresponders, sputum eosinophils also significantly increased after ozone. There was a positive correlation between ozone-induced FEV1 fall and increase in sputum neutrophils. No difference in functional or inflammatory response to ozone was observed between subjects with or without the combination of NQO1wt- GSTM1null genotypes. Conclusions Markers of neutrophilic inflammation and oxidative stress increase also in asthmatic subjects not responding to ozone. A greater functional response to ozone is associated with greater neutrophil airway recruitment in asthmatic subjects.

  7. Functional high-resolution computed tomography of pulmonary vascular and airway reactions. Experimental results. Funktionelle HR-CT der Lunge. Experimentelle Untersuchungen pulmonaler Gefaess- und Atemwegsreaktionen

    Energy Technology Data Exchange (ETDEWEB)

    Herold, C.J. (Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria) Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology); Brown, R.H. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Physiology); Wetzel, R.C.; Herold, S.M. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine); Zeerhouni, E.A. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology)

    1993-03-01

    We describe the use of high-resolution computed tomography (HRCT) for assessment of the function of pulmonary vessels and airways. With its excellent spatial resolution, HRCT is able to demonstrate pulmonary structures as small as 300 [mu]m and can be used to monitor changes following various stimuli. HRCT also provides information about structures smaller than 300 [mu]m through measurement of parenchymal background density. To date, sequential, spiral and ultrafast HRCT techniques have been used in a variety of challenges to gather information about the anatomical correlates of traditional physiological measurements, thus making anatomical-physiological correlation possible. HRCT of bronchial reactivity can demonstrate the location and time course of aerosol-induced broncho-constriction and may show changes not apparent on spirometry. HRCT of the pulmonary vascular system visualized adaptations of vessels during hypoxia and intravascular volume loading and elucidates cardiorespiratory interactions. Experimental studies provide a basis for potential clinical applications of this method. (orig.).

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Does hyperbaric oxygen therapy prevent airway anastomosis from breakdown?

    NARCIS (Netherlands)

    Dickhoff, C.; Daniels, J.M.; Brink, A. van den; Paul, M.A.; Verhagen, A.F.T.M.

    2015-01-01

    Ischemia with subsequent necrosis of anastomoses, after central airway resection and reconstruction, remains a feared complication for thoracic surgeons and their patients. To date, there is no evidence to support the use of hyperbaric oxygen in the prevention of necrosis of airway reconstructions i

  10. 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) w

  11. Mutational analysis of the structure basis for the multimerization function of NifA central domain

    Institute of Scientific and Technical Information of China (English)

    YANG; Chengtao; (杨成涛); YU; Guanqiao; (俞冠翘); SHEN; Shanjiong; (San-Chiun; Shen,; 沈善炯); ZHU; Jiabi; (朱家璧)

    2001-01-01

    In Klebsiella pneumoniae (Kp) NifA central domain, when the conservative amino acid residue Thr-290 in C3 region was replaced by Val, the function of NifA for activating the transcription of nif genes was lost. Thus the conservative Thr-290 residue seems critical for the activation function of NifA central domain. This point mutant of NifA central domain is used to examine the putative multimerization function of NifA central domain by merodiploid experiment. The results showed that the NifA central domain bore the multimerization determinants of NifA protein. A series of truncated mutants of NifA were constructed to determine the structural elements at the central domain critical for multimerization. It demonstrates that amino acid residues 252-453 are involved in the multimerization function of NifA central domain.

  12. Mutational analysis of the structure basis for the multimerization function of NifA central domain

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In Klebsiella pneumoniae (Kp) NifA central domain, when theconservative amino acid residue Thr-290 in C3 region was replaced by Val, the function of NifA for activating the transcription of nif genes was lost. Thus the conservative Thr-290 residue seems critical for the activation function of NifA central domain. This point mutant of NifA central domain is used to examine the putative multimerization function of NifA central domain by merodiploid experiment. The results showed that the NifA central domain bore the multimerization determinants of NifA protein. A series of truncated mutants of NifA were constructed to determine the structural elements at the central domain critical for multimerization. It demonstrates that amino acid residues 252-453 are involved in the multimerization function of NifA central domain.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Mucolytic treatment with N-acetylcysteine L-lysinate metered dose inhaler in dogs: airway epithelial function changes.

    Science.gov (United States)

    Tomkiewicz, R P; App, E M; Coffiner, M; Fossion, J; Maes, P; King, M

    1994-01-01

    N-acetylcysteine L-lysinate Nacystelyn (L-NAC) is a newly synthesized mucolytic agent, of which the action in vivo has not been well defined. In six healthy mongrel dogs, the rheological properties of mucus, its mucociliary and cough clearability, and the transepithelial potential difference (PD) of the tracheobronchial epithelium were evaluated after placebo and L-NAC metered dose inhaler (MDI) aerosols. The principal index of mucus rigidity, log G*, decreased at all airway sites with L-NAC administration, i.e. the mucus became less rigid and more deformable (the overall change in G* was 0.29 log units, i.e. ca. twofold decrease). The viscoelasticity-derived mucus transportability parameters, mucociliary (MCI) and cough (CCI) clearability indices, increased with L-NAC MDI, particularly CCI, which predicts the effect of mucus rheology on cough clearability. PD increased significantly with L-NAC administration at all measurement sites, which appears to be a novel effect for a direct acting mucolytic agent. Tracheal mucus linear velocity (TMV) increased after L-NAC compared with placebo, as did the normalized frog palate transport rate (NFPTR). The increase in NFPTR was greater than that predicted from the mucus rheological properties alone, suggesting that L-NAC still resident in the collected mucus stimulated the frog palate cilia. The index of mucus flux, the collection rate in mg.min-1, was higher with L-NAC compared with placebo. From our results, we conclude that L-NAC shows potential benefit in terms of improving mucus rheological properties and clearability. It may act, in part, by stimulating the fresh secretion of mucus of lower viscoelasticity. The stimulation of mucociliary clearance could be related to ion flux changes, as indicated by the increase in PD.

  15. Airway management in trauma

    Directory of Open Access Journals (Sweden)

    Rao B

    2004-01-01

    Full Text Available Airway Management for the victims of major trauma is the first priority in the care of the trauma victim and is a core skill in emergency medicine and critical care. Endotracheal intubation remains the gold standard for trauma airway management. Airway management in trauma patients is not just the capability to insert an oral/nasal airway or endotracheal tube beyond the vocal cords. The five components integral to modern, sophisticated airway management in trauma patients include equipment, pharmacologic adjuncts, manual techniques, physical circumstances, and patient profile. A trauma patient may require airway management in a variety of physical circumstances. Whereas, the commonly used airway management algorithms may not suffice in all these situations, the construction of a truly complete decision tree is also virtually impossible. There is consensus that it is not the intervention per se but rather the conditions, skills, and performance that might be the possible variables that affect outcome. Paramedics have only limited experience and on-the-job skills for invasive airway management. Difficult airway management is best left for the experienced physicians to handle.

  16. Measurement of intraindividual airway tone heterogeneity and its importance in asthma.

    Science.gov (United States)

    Brown, Robert H; Togias, Alkis

    2016-07-01

    While airways have some degree of baseline tone, the level and variability of this tone is not known. It is also unclear whether there is a difference in airway tone or in the variability of airway tone between asthmatic and healthy individuals. This study examined airway tone and intraindividual airway tone heterogeneity (variance of airway tone) in vivo in 19 individuals with asthma compared with 9 healthy adults. All participants underwent spirometry, body plethysmography, and high-resolution computed tomography at baseline and after maximum bronchodilation with albuterol. Airway tone was defined as the percent difference in airway diameter after albuterol at total lung capacity compared with baseline. The amount of airway tone in each airway varied both within and between subjects. The average airway tone did not differ significantly between the two groups (P = 0.09), but the intraindividual airway tone heterogeneity did (P = 0.016). Intraindividual airway tone heterogeneity was strongly correlated with airway tone (r = 0.78, P tone heterogeneity and conventional lung function outcomes. Intraindividual airway tone heterogeneity appears to be an important characteristic of airway pathophysiology in asthma.

  17. Peptides with a dual function: Central neuroregulators and gut hormones

    NARCIS (Netherlands)

    Loonen, A.J.M.; Soudijn, W.

    1979-01-01

    The present article deals with peptides which are present in the CNS and in various peripheral tissues in neuronal as well as in endocrine cells. The regional distribution within the central nervous system is analysed, the cellular structures in which they are found are summarized and their actions

  18. Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma.

    Science.gov (United States)

    Firszt, Rafael; Francisco, Dave; Church, Tony D; Thomas, Joseph M; Ingram, Jennifer L; Kraft, Monica

    2014-02-01

    Airway remodelling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodelling is subepithelial fibrosis. Interleukin (IL)-13 is a key T-helper 2 cytokine and is believed to be the central mediator of allergic asthma including remodelling, but the mechanism driving the latter has not been elucidated in human asthma. We hypothesised that IL-13 stimulates collagen type-1 production by the airway fibroblast in a matrix metalloproteinase (MMP)- and transforming growth factor (TGF)-β1-dependent manner in human asthma as compared to healthy controls. Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors. IL-13 significantly stimulated collagen type-1 production in asthma compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-β1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls. In an ex vivo model, IL-13 potentiates airway remodelling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodelling in asthma.

  19. Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Wang H

    2016-09-01

    correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC, FEV1/Pre (justified r=-0.308, P<0.001; justified r=-0.295, P=0.001, respectively and SAO indicators such as FEV3/FVC, MMEF25–75/Pre (justified r=-0.289, P=0.001; justified r=-0.273, P=0.002, respectively, but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001, the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively. Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1. Conclusion: Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD. Keywords: plasminogen activator inhibitor-1 (PAI-1, chronic obstructive pulmonary disease (COPD, systemic inflammation, small airway obstruction (SAO

  20. An almost Sure Central Limit Theorem for the Weight Function Sequences of NA Random Variables

    Indian Academy of Sciences (India)

    Qunying Wu

    2011-08-01

    Consider the weight function sequences of NA random variables. This paper proves that the almost sure central limit theorem holds for the weight function sequences of NA random variables. Our results generalize and improve those on the almost sure central limit theorem previously obtained from the i.i.d. case to NA sequences.

  1. Indirect airway challenges

    NARCIS (Netherlands)

    Joos, GF; O'Connor, B; Anderson, SD; Chung, F; Cockcroft, DW; Dahlen, B; DiMaria, G; Foresi, A; Hargreave, FE; Holgate, ST; Inman, M; Lotvall, J; Magnussen, H; Polosa, R; Postma, DS; Riedler, J

    2003-01-01

    Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Di

  2. Pediatric airway nightmares.

    Science.gov (United States)

    D'Agostino, James

    2010-02-01

    Pediatric disorders that involve actual or potential airway compromise are among the most challenging cases that emergency department providers face. This article discusses the diagnosis and management of common and uncommon conditions in infants and children who may present with airway obstruction.

  3. Impact of airway morphological changes on pulmonary flows in scoliosis

    Science.gov (United States)

    Farrell, James; Garrido, Enrique; Valluri, Prashant

    2016-11-01

    The relationship between thoracic deformity in scoliosis and lung function is poorly understood. In a pilot study, we reviewed computed tomography (CT) routine scans of patients undergoing scoliosis surgery. The CT scans were processed to segment the anatomy of the airways, lung and spine. A three-dimensional model was created to study the anatomical relationship. Preliminary analysis showed significant airway morphological differences depending on the anterior position of the spine. A computational fluid dynamics (CFD) study was also conducted on the airway geometry using the inspiratory scans. The CFD model assuming non-compliant airway walls was capable of showing pressure drops in areas of high airway resistance, but was unable to predict regional ventilation differences. Our results indicate a dependence between the dynamic deformation of the airway during breathing and lung function. Dynamic structural deformation must therefore be incorporated within any modelling approaches to guide clinicians on the decision to perform surgical correction of the scoliosis.

  4. Dual function of novel pollen coat (surface proteins: IgE-binding capacity and proteolytic activity disrupting the airway epithelial barrier.

    Directory of Open Access Journals (Sweden)

    Mohamed Elfatih H Bashir

    Full Text Available BACKGROUND: The pollen coat is the first structure of the pollen to encounter the mucosal immune system upon inhalation. Prior characterizations of pollen allergens have focused on water-soluble, cytoplasmic proteins, but have overlooked much of the extracellular pollen coat. Due to washing with organic solvents when prepared, these pollen coat proteins are typically absent from commercial standardized allergenic extracts (i.e., "de-fatted", and, as a result, their involvement in allergy has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: Using a unique approach to search for pollen allergenic proteins residing in the pollen coat, we employed transmission electron microscopy (TEM to assess the impact of organic solvents on the structural integrity of the pollen coat. TEM results indicated that de-fatting of Cynodon dactylon (Bermuda grass pollen (BGP by use of organic solvents altered the structural integrity of the pollen coat. The novel IgE-binding proteins of the BGP coat include a cysteine protease (CP and endoxylanase (EXY. The full-length cDNA that encodes the novel IgE-reactive CP was cloned from floral RNA. The EXY and CP were purified to homogeneity and tested for IgE reactivity. The CP from the BGP coat increased the permeability of human airway epithelial cells, caused a clear concentration-dependent detachment of cells, and damaged their barrier integrity. CONCLUSIONS/SIGNIFICANCE: Using an immunoproteomics approach, novel allergenic proteins of the BGP coat were identified. These proteins represent a class of novel dual-function proteins residing on the coat of the pollen grain that have IgE-binding capacity and proteolytic activity, which disrupts the integrity of the airway epithelial barrier. The identification of pollen coat allergens might explain the IgE-negative response to available skin-prick-testing proteins in patients who have positive symptoms. Further study of the role of these pollen coat proteins in allergic

  5. Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Chen-Chen Lee

    2015-01-01

    Full Text Available This study investigated the immunomodulatory effects of ferulic acid (FA on antigen-presenting dendritic cells (DCs in vitro and its antiallergic effects against ovalbumin- (OVA- induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS stimulation induced a high level of interleukin- (IL- 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF- α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4, MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13, and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN- γ production in bronchoalveolar lavage fluid (BALF and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

  6. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  7. Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Carla M. P. Ribeiro

    2017-01-01

    Full Text Available Cystic fibrosis (CF pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR. This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes. These findings suggest that targeting the IRE1/XBP-1 UPR pathway may be a therapeutic strategy for CF airway disease.

  8. The relationship between inspiratory lung function parameters and airway hyper-responsiveness in subjects with mild to moderate COPD

    NARCIS (Netherlands)

    S.K. Ramlal (Sunil); F.J. Visser (Frank); W.C.J. Hop (Wim); B. Staffhorst (Bas); P.N.R. Dekhuijzen (Richard); Y.F. Heijdra (Yvonne)

    2012-01-01

    textabstractBackground: The aim of this study was to evaluate the effects of increasing doses of inhaled histamine on the forced expiratory volume in one second (FEV 1), inspiratory lung function parameters (ILPs) and dyspnea in subjects with mild to moderate chronic obstructive pulmonary disease (C

  9. Reorganization of early visual cortex functional connectivity following selective peripheral and central visual loss.

    Science.gov (United States)

    Sabbah, Norman; Sanda, Nicolae; Authié, Colas N; Mohand-Saïd, Saddek; Sahel, José-Alain; Habas, Christophe; Amedi, Amir; Safran, Avinoam B

    2017-02-24

    Behavioral alterations emerging after central or peripheral vision loss suggest that cerebral reorganization occurs for both the afferented and deafferented early visual cortex (EVC). We explored the functional reorganization of the central and peripheral EVC following visual field defects specifically affecting central or peripheral vision. Compared to normally sighted, afferented central and peripheral EVC enhance their functional connectivity with areas involved in visual processing, whereas deafferented central and peripheral EVC increase their functional connectivity with more remote regions. The connectivity pattern of afferented EVC suggests adaptive changes that might enhance the visual processing capacity whereas the connectivity pattern of deafferented EVC may reflect the involvement of these regions in high-order mechanisms. Characterizing and understanding the plastic changes induced by these visual defects is essential for any attempt to develop efficient rehabilitation strategies.

  10. Temperature regulates methane production through the function centralization of microbial community in anaerobic digestion.

    Science.gov (United States)

    Lin, Qiang; De Vrieze, Jo; He, Guihua; Li, Xiangzhen; Li, Jiabao

    2016-09-01

    Temperature is crucial for the performance of anaerobic digestion process. In this study of anaerobic digestion of swine manure, the relationship between the microbial gene expression and methane production at different temperatures (25-55°C) was revealed through metatranscriptomic analysis. Daily methane production and total biogas production increased with temperature up to 50°C, but decreased at 55°C. The functional gene expression showed great variation at different temperatures. The function centralization (opposite to alpha-diversity), assessed by the least proportions of functional pathways contributing for at least 50% of total reads positively correlated to methane production. Temperature regulated methane production probably through reducing the diversity of functional pathways, but enhancing central functional pathways, so that most of cellular activities and resource were invested in methanogenesis and related pathways, enhancing the efficiency of conversion of substrates to methane. This research demonstrated the importance of function centralization for efficient system functioning.

  11. Emergency airway puncture - slideshow

    Science.gov (United States)

    ... presentations/100113.htm Emergency airway puncture - series—Normal anatomy To ... larynx is a tubular structure in the neck, through which air passes to the lungs. The thryoid and cricoid cartilage form the narrowest ...

  12. Emergency airway puncture

    Science.gov (United States)

    ... inserted into the throat, just below the Adam's apple (cricoid cartilage), into the airway. In a hospital, ... Choking Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the ...

  13. Elafin在气道炎症性疾病中的作用%Functions of Elafin in airway inflammatory disease

    Institute of Scientific and Technical Information of China (English)

    邓玥; 张婷; 周向东

    2014-01-01

    Elafin is an endogeneous low molecular weight inhibitor of serine proteases.It is derived from a precursor,trappin-2 or pre-Elafin by proteolysis.Elafin has a unique N-terminal domain that enables it to become cross-linked to extracellular matrix proteins by transglutaminase,while retaining its inhibitory activity.Elafin has many biological functions as diverse as anti-bacterial,anti-fungal,anti-viral,anti-inflammatory,and immuno-modulatory functions,in addition to its inhibitory activity.Hence,Elafin has become an attractive candidate as therapeutic molecule in inflammatory lung disease.%Elafin是一种内源性的低分子量丝氨酸蛋白酶抑制剂,它来自于其前体trappin-2(或称pre-Elafin)的蛋白水解.Elafin的N端区段可以在转谷酰胺酶的介导下与细胞外基质铰连,而C端可以继续发挥抗蛋白酶作用.此外,Elafin还有抗感染、抗炎和免疫调节作用.因此,在气道炎症性疾病的治疗方面,Elafin是一种极具吸引力的候选分子.

  14. 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.

  15. The functional central limit theorem for strong near-epoch dependent random variables

    Institute of Scientific and Technical Information of China (English)

    QIU Jin; LIN Zhengyan

    2004-01-01

    The functional central limit theorem for strong near-epoch dependent sequences of random variables is proved.The conditions given improve on previous results in the literature concerning dependence and heterogeneity.

  16. Central swallowing in normal adults using functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Shasha Li; Cheng Luo; Chengqi He; Qiyong Gong; Dong Zhou

    2009-01-01

    BACKGROUND: While brain-imaging studies in healthy adults have indicated that multiple cortical regions are involved in swallowing, these functional imaging techniques have not been extensively applied to the complete understand neurophysiology of swallowing in China. A full understanding of normal swallowing neurophysiology is important for improving functional outcomes for dysphagia due to neurologic disorders or damage with increasing age. Thus the interpretations of the functional contributions of various brain areas in swallowing should be scientifically researched.OBJECTIVE: To identify the activation and characteristic of swallowing center in healthy adults using functional magnetic resonance imaging.DESIGN, TIME AND SETTING: An uncontrolled neuroimaging study was performed at the Outpatient Clinic, Department of Radiology, West China Hospital of Sichuan University between March and November 2008.PARTICIPANTS: Ten healthy right-handed volunteers, aged over 20 years with a mean age of (34.2 ±8.1) years, a range of 25-45 years and including five males and five females participated. A medical history was obtained from all potential subjects and all subjects were free of systemic diseases and neurological disorders.METHODS: The healthy volunteers were examined with event-related functional magnetic resonance imaging of blood oxygenation level-dependent while laryngeal swallow-related movements were recorded. Subjects were scanned during voluntary saliva swallowing and water bolus swallowing activation tasks. Data was processed using the General Linear Model. A voxel by voxel group comparison was performed using random effect analysis. Any cluster with a corrected P < 0.05 for spatial extent was considered significant.MAIN OUTCOME MEASURES: The cerebral cortical activation maps of voluntary swallowing of saliva and swallowing of water bolus in healthy adults were observed.RESULTS: A multifocal cortical representation of swallowing was in the precentral gyrus

  17. Monetary Policy and Foreign Exchange Management: Reforming Central Bank Functions in Myanmar

    OpenAIRE

    Nijathaworn, Bandid; Chaikhor, Suwatchai; Chotika-arpa, Suppakorn; Sakkankosone, Suchart

    2015-01-01

    Myanmar’s macroeconomic policy framework does not adequately support the new functions of the Central Bank of Myanmar. The monetary policy regime is deficient and institutions that complement the working of a market-based economy lacking. This paper identifies 10 priority areas for reform to allow the central bank to effectively perform its emerging new functions in support of economic growth and stability. This is a three-front effort: dismantle nonmarket arrangements, especially in the fina...

  18. Monetary Policy and Foreign Exchange Management: Reforming Central Bank Functions in Myanmar

    OpenAIRE

    Nijathaworn, Bandid; Chaikhor, Suwatchai; Chotika-arpa, Suppakorn; Sakkankosone, Suchart

    2015-01-01

    Myanmar's macroeconomic policy framework does not adequately support the new functions of the Central Bank of Myanmar. The monetary policy regime is deficient and institutions that complement the working of a market-based economy lacking. This paper identifies 10 priority areas for reform to allow the central bank to effectively perform its emerging new functions in support of economic growth and stability. This is a three-front effort: dismantle nonmarket arrangements, especially in the fina...

  19. Airway inflammation and peripheral airway function in asthmatic patients with different control levels%不同控制水平的支气管哮喘患者气道炎症与外周气道功能状态的研究

    Institute of Scientific and Technical Information of China (English)

    潘杨; 黄克武; 叶青; 刘学松; 武宝梅; 张君; 常晓红; 逯勇; 王辰

    2009-01-01

    Objective To observe the airway inflammation and peripheral airway function in asthmatic patients with different control levels, and to investigate whether the airway inflammation profile detected by induced sputum reflects the peripheral airway dysfunction. Methods The recruited asthmatic subjects (n=66) were divided into 3 groups: asthma controlled (8 male and 13 female), asthma partly controlled (12 male and 16 female), asthma uncontrolled (6 male and 11 female). Twenty healthy subjects served as the control group (9 male and 11 female). On the 1st day, all the subjects were required to take asthma control test (ACT), and to receive measurement of lung function by osciilometry and spirometry as well as inflammatory cell profile of induced sputum and the concentration of eosinophil cationic protein (ECP). Exhaled nitric oxide (Feso) was measured on the 2nd day, and oscillometry methacholine provocation was conducted for patients whose baseline FEV_1 was ≥70% predicted. The provocation process was terminated when airway resistance was increased by twice of the basic value, or when the mcthacholine reached the highest concentration. Then airway resistance and lung function were examined after 3 minutes. Finally, airway resistance and lung function were measured again after the subjects had 5 consecutive deep inspirations (DI). Correlation analysis was conducted between ACT scores and inflammatory cells count, ECP concentrations of induced sputum and FE_(NO) among different groups. The correlations were also made between the change of peripheral airway resistance triggered by provocation or DI and ACT scores, total eosinophil, ECP level of induced sputum, FE_(NO) respectively. Results The total eosinophil count and ECP level in induced sputum and FE_(NO) in asthmatic patients increased with the decline of control level. Negative correlations between ACT scores and total eosinophil count as well as the ECP level were observed (r = -0.43, -0.56, P 0.05) with

  20. In vivo models of human airway epithelium repair and regeneration

    Directory of Open Access Journals (Sweden)

    C. Coraux

    2005-12-01

    Full Text Available Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study 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 reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.

  1. DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

    Science.gov (United States)

    Habibovic, Aida; Hristova, Milena; Heppner, David E.; Danyal, Karamatullah; Ather, Jennifer L.; Janssen-Heininger, Yvonne M.W.; Irvin, Charles G.; Poynter, Matthew E.; Lundblad, Lennart K.; Dixon, Anne E.; Geiszt, Miklos

    2016-01-01

    Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite–induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1). DUOX1 deficiency also attenuated several EGFR-dependent features of HDM-induced allergic airway inflammation, including neutrophilic inflammation, type 2 cytokine production (IL-33, IL-13), mucous metaplasia, subepithelial fibrosis, and central airway resistance. Moreover, targeted inhibition of airway DUOX1 in mice with previously established HDM-induced allergic inflammation, by intratracheal administration of DUOX1-targeted siRNA or pharmacological NADPH oxidase inhibitors, reversed most of these outcomes. Our findings indicate an important function for DUOX1 in allergic inflammation related to persistent EGFR activation and suggest that DUOX1 targeting may represent an attractive strategy in asthma management.

  2. Quantitative computed tomography imaging of airway remodeling in severe asthma.

    Science.gov (United States)

    Grenier, Philippe A; Fetita, Catalin I; Brillet, Pierre-Yves

    2016-02-01

    Asthma is a heterogeneous condition and approximately 5-10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively.

  3. Central nicotinic receptors: structure, function, ligands, and therapeutic potential.

    Science.gov (United States)

    Romanelli, M Novella; Gratteri, Paola; Guandalini, Luca; Martini, Elisabetta; Bonaccini, Claudia; Gualtieri, Fulvio

    2007-06-01

    The growing interest in nicotinic receptors, because of their wide expression in neuronal and non-neuronal tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so far, only compounds showing selectivity between alpha4beta2 and alpha7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high-throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.

  4. Development and application of pulmonary structure-function registration methods: towards pulmonary image-guidance tools for improved airway targeted therapies and outcomes

    Science.gov (United States)

    Guo, Fumin; Pike, Damien; Svenningsen, Sarah; Coxson, Harvey O.; Drozd, John J.; Yuan, Jing; Fenster, Aaron; Parraga, Grace

    2014-03-01

    Objectives: We aimed to develop a way to rapidly generate multi-modality (MRI-CT) pulmonary imaging structurefunction maps using novel non-rigid image registration methods. This objective is part of our overarching goal to provide an image processing pipeline to generate pulmonary structure-function maps and guide airway-targeted therapies. Methods: Anatomical 1H and functional 3He MRI were acquired in 5 healthy asymptomatic ex-smokers and 7 ex-smokers with chronic obstructive pulmonary disease (COPD) at inspiration breath-hold. Thoracic CT was performed within ten minutes of MRI using the same breath-hold volume. Landmark-based affine registration methods previously validated for imaging of COPD, was based on corresponding fiducial markers located in both CT and 1H MRI coronal slices and compared with shape-based CT-MRI non-rigid registration. Shape-based CT-MRI registration was developed by first identifying the shapes of the lung cavities manually, and then registering the two shapes using affine and thin-plate spline algorithms. We compared registration accuracy using the fiducial localization error (FLE) and target registration error (TRE). Results: For landmark-based registration, the TRE was 8.4±5.3 mm for whole lung and 7.8±4.6 mm for the R and L lungs registered independently (p=0.4). For shape-based registration, the TRE was 8.0±4.6 mm for whole lung as compared to 6.9±4.4 mm for the R and L lung registered independently and this difference was significant (p=0.01). The difference for shape-based (6.9±4.4 mm) and landmark-based R and L lung registration (7.8±4.6 mm) was also significant (p=.04) Conclusion: Shape-based registration TRE was significantly improved compared to landmark-based registration when considering L and R lungs independently.

  5. Effect of continuous positive airway pressure treatment on vascular endothelial function in patients with obstructive sleep apnea hypopnea syndrome and coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    张希龙; 殷凯生; 毛辉; 王虹; 杨玉

    2004-01-01

    Background Continuous positive airway pressure (CPAP) treatment has been proven to be effective in improving the symptoms of coexisting coronary heart disease (CHD) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, it is still unclear whether such improvements are linked to changes in vascular endothelial function. This research was carried out to investigate the effects of CPAP treatment on vascular endothelial function in patients with OSAHS and CHD.Methods Thirty-six patients with moderate or severe OSAHS and CHD undergoing three months of CPAP treatment were recruited for this study. The changes in their morning plasma nitric oxide (NO) and endothelin (ET) levels, NO/ET ratio, total ischemic burden (TIB) of the myocardium, apnea hypopnea index (AHI), and minimal and mean pulse oxygen saturation (SpO2) were compared and analyzed before and during CPAP treatment. Results Compared with the plasma levels of ET [(51.39±11.69) ng/L] and NO [(36.67±11.86) μmol/L], NO/ET (0.71±0.14), AHI (32.4±7.9), minimal SpO2 [(68.9±11.4)%], and myocardial TIB [(66.29±16.37) mm*min] before treatment, there were significant decreases in ET [(33.41±10.03) ng/L] (P<0.05), increases in NO [(59.89±10.26) μmol/L] and NO/ET (1.79±0.38) (P<0.01), decreases in AHI (1.9±0.5), and increases in minimal SpO2 [(90.6±1.8) %] (all P<0.01) and myocardial TIB [(36.42±10.87) mm*min] (P<0.05) after three months of CPAP treatment.Conclusion CPAP treatment may play an important role in the improvement and protection of vascular endothelial dysfunction and myocardial ischemia in OSAHS patients with CHD.

  6. 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.

    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 ad

  7. Airway reconstruction in children

    Directory of Open Access Journals (Sweden)

    Rao Sanjay

    2009-01-01

    Full Text Available Aim/Background : Airway anomalies are infrequent but potentially life threatening in children. A program to care for these difficult children was set up at our institution, and this paper summarizes our experience. Methods: A total of 34 children were enrolled in the program over a period of three years. These children were evaluated as per the standard protocols. Treatment was individualized. Results: Of these 34 children, 28 had their airways restored and are doing well. Four children continue to remain on tracheostomy and two will require long term tracheostomy. There were two deaths. All children are under surveillance as there is a risk of recurrence. Conclusions: Airway anomalies are complex problems with significant morbidity and mortality. Current therapeutic modalities allow for good results. Most children were successfully decannulated and did well.

  8. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

    2011-04-22

    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical

  9. Paediatric airway management: basic aspects

    DEFF Research Database (Denmark)

    Holm-Knudsen, R J; Rasmussen, L S

    2009-01-01

    . Airway obstruction can be avoided by paying close attention to the positioning of the head of the child and by keeping the mouth of the child open during mask ventilation. The use of oral and nasopharyngeal airways, laryngeal mask airways, and cuffed endotracheal tubes is discussed with special reference...... to the circumstances in infants. A slightly different technique during laryngoscopy is suggested. The treatment of airway oedema and laryngospasm is described....

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Insect-Like Organization of the Stomatopod Central Complex: Functional and Phylogenetic Implications

    Science.gov (United States)

    Thoen, Hanne H.; Marshall, Justin; Wolff, Gabriella H.; Strausfeld, Nicholas J.

    2017-01-01

    One approach to investigating functional attributes of the central complex is to relate its various elaborations to pancrustacean phylogeny, to taxon-specific behavioral repertoires and ecological settings. Here we review morphological similarities between the central complex of stomatopod crustaceans and the central complex of dicondylic insects. We discuss whether their central complexes possess comparable functional properties, despite the phyletic distance separating these taxa, with mantis shrimp (Stomatopoda) belonging to the basal branch of Eumalacostraca. Stomatopods possess the most elaborate visual receptor system in nature and display a fascinating behavioral repertoire, including refined appendicular dexterity such as independently moving eyestalks. They are also unparalleled in their ability to maneuver during both swimming and substrate locomotion. Like other pancrustaceans, stomatopods possess a set of midline neuropils, called the central complex, which in dicondylic insects have been shown to mediate the selection of motor actions for a range of behaviors. As in dicondylic insects, the stomatopod central complex comprises a modular protocerebral bridge (PB) supplying decussating axons to a scalloped fan-shaped body (FB) and its accompanying ellipsoid body (EB), which is linked to a set of paired noduli and other recognized satellite regions. We consider the functional implications of these attributes in the context of stomatopod behaviors, particularly of their eyestalks that can move independently or conjointly depending on the visual scene. PMID:28223924

  12. Quantitative analysis of airway abnormalities in CT

    DEFF Research Database (Denmark)

    Petersen, Jens; Lo, Pechin Chien Pau; Nielsen, Mads;

    2010-01-01

    A coupled surface graph cut algorithm for airway wall segmentation from Computed Tomography (CT) images is presented. Using cost functions that highlight both inner and outer wall borders, the method combines the search for both borders into one graph cut. The proposed method is evaluated on 173 ...

  13. Altered Epithelial Gene Expression in Peripheral Airways of Severe Asthma

    Science.gov (United States)

    Singhania, Akul; Rupani, Hitasha; Jayasekera, Nivenka; Lumb, Simon; Hales, Paul; Gozzard, Neil; Davies, Donna E.

    2017-01-01

    Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study. Differences between central and peripheral airways were evaluated using transcriptomic analysis (Affymetrix HG U133 plus 2.0 GeneChips) of epithelial brushings obtained from severe asthma patients (N = 17) and healthy volunteers (N = 23). Results were validated in an independent cohort (N = 10) by real-time quantitative PCR. The IL-13 disease signature that is associated with an asthmatic phenotype was upregulated in severe asthmatics compared to healthy controls but was predominantly evident within the peripheral airways, as were genes related to mast cell presence. The gene expression response associated with glucocorticosteroid therapy (i.e. FKBP5) was also upregulated in severe asthmatics compared to healthy controls but, in contrast, was more pronounced in central airways. Moreover, an altered epithelial repair response (e.g. FGFBP1) was evident across both airway sites reflecting a significant aspect of disease in severe asthma unadressed by current therapies. A transcriptomic approach to understand epithelial activation in severe asthma has thus highlighted the need for better-targeted therapy to the peripheral airways in severe asthma, where the IL-13 disease signature persists despite treatment with currently available therapy. PMID:28045928

  14. Pharmacological studies of the mechanism and function of interleukin-1β-induced miRNA-146a expression in primary human airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Jiang Xiaoying

    2010-06-01

    Full Text Available Abstract Background Despite the widespread induction of miR-146a during the innate immune response little is known regarding its biogenesis, function and mechanism. We have therefore examined the role of miR-146a during the interleukin (IL-1β-stimulated IL-6 and IL-8 release and proliferation in primary human airway smooth muscle (HASM cells. Methods HASM cells were isolated from human lung re-section, cultured to a maximum of 3 - 6 passages and then exposed to IL-1β. miR-146a expression were determined by qRT-PCR, IL-6 and IL-8 release by ELISA and proliferation using bromodeoxyuridine incorporation. The role of NF-κB and the MAP kinase pathways was assessed using pharmacological inhibitors of IKK2 (TPCA-1, JNK (SP600125, p38 MAP kinase (SB203580 and MEK-1/2 (PD98059. miR-146a function was determined following transfection of HASM with inhibitors and mimics using Amaxa electroporation. Results IL-1β induced a time-dependent and prolonged 100-fold induction in miR-146a expression, which correlated with release of IL-6 and IL-8. Exposure to IL-1β had no effect upon HASM proliferation. Pharmacological studies showed that expression of primary miR-146a was regulated at the transcriptional levels by NF-κB whilst post-transcriptional processing to mature miR-146a was regulated by MEK-1/2 and JNK-1/2. Functional studies indicated that IL-1β-induced miR-146a expression does not negatively regulate IL-6 and IL-8 release or basal proliferation. However, inhibition of IL-1β-induced IL-6 and IL-8 release was observed at the super-maximal intracellular miR-146a levels obtained by transfection with miR-146a mimics and indicates that studies using miRNA mimics can produce false positive results. Mechanistic studies showed that in the presence of super-maximal levels, the action of miR-146a mimics was mediated at a step following IL-6 and IL-8 mRNA transcription and not through down-regulation of IL-1 receptor associated kinase 1 (IRAK-1 and TNF

  15. A comparison of a new mucolytic N-acetylcysteine L-lysinate with N-acetylcysteine: airway epithelial function and mucus changes in dog.

    Science.gov (United States)

    Tomkiewicz, R P; App, E M; De Sanctis, G T; Coffiner, M; Maes, P; Rubin, B K; King, M

    1995-12-01

    A newly synthesized mucolytic agent, N-acetylcysteine L-lysinate (Nacystelyn) was studied. Tracheal mucus velocity (TMV), transepithelial potential difference (PD), rheological properties, and ion content of collected airway secretions were evaluated in six healthy mongrel dogs after placebo, Nacystelyn (NAL) and acetylcysteine (NAC) metered dose inhaler (MDI) aerosols. Although TMV was increased and viscoelasticity decreased after both treatments, the treatment effect with NAL was significantly greater. Furthermore, NAL increased the negative PD and CI- content of secretions in the trachea, an effect not observed after NAC. Both compounds increased ciliary beat frequency (CBF) on the frog palate at a concentration range similar to that approximated in dog airways. The increased mucociliary clearance could be partially explained by favourable rheological changes combined with stimulation of CBF. Since both compounds break disulfide bonds in mucus polymers, the greater change in mucus rheology and clearance rate after NAL, without change in water content, could be explained by the increase in CI- content. Nacystelyn appears to combine different modes of action which synergistically cause an increase in the clearance rate of airway secretions.

  16. Decreased centrality of subcortical regions during the transition to adolescence: a functional connectivity study.

    Science.gov (United States)

    Sato, João Ricardo; Salum, Giovanni Abrahão; Gadelha, Ary; Vieira, Gilson; Zugman, André; Picon, Felipe Almeida; Pan, Pedro Mario; Hoexter, Marcelo Queiroz; Anés, Mauricio; Moura, Luciana Monteiro; Del'Aquilla, Marco Antonio Gomes; Crossley, Nicolas; Amaro Junior, Edson; Mcguire, Philip; Lacerda, Acioly L T; Rohde, Luis Augusto; Miguel, Euripedes Constantino; Jackowski, Andrea Parolin; Bressan, Rodrigo Affonseca

    2015-01-01

    Investigations of brain maturation processes are a key step to understand the cognitive and emotional changes of adolescence. Although structural imaging findings have delineated clear brain developmental trajectories for typically developing individuals, less is known about the functional changes of this sensitive development period. Developmental changes, such as abstract thought, complex reasoning, and emotional and inhibitory control, have been associated with more prominent cortical control. The aim of this study is to assess brain networks connectivity changes in a large sample of 7- to 15-year-old subjects, testing the hypothesis that cortical regions will present an increasing relevance in commanding the global network. Functional magnetic resonance imaging (fMRI) data were collected in a sample of 447 typically developing children from a Brazilian community sample who were submitted to a resting state acquisition protocol. The fMRI data were used to build a functional weighted graph from which eigenvector centrality (EVC) was extracted. For each brain region (a node of the graph), the age-dependent effect on EVC was statistically tested and the developmental trajectories were estimated using polynomial functions. Our findings show that angular gyrus become more central during this maturation period, while the caudate; cerebellar tonsils, pyramis, thalamus; fusiform, parahippocampal and inferior semilunar lobe become less central. In conclusion, we report a novel finding of an increasing centrality of the angular gyrus during the transition to adolescence, with a decreasing centrality of many subcortical and cerebellar regions.

  17. Effects of physical exercise on central nervous system functions: a review of brain region specific adaptations.

    Science.gov (United States)

    Morgan, Julie A; Corrigan, Frances; Baune, Bernhard T

    2015-01-01

    Pathologies of central nervous system (CNS) functions are involved in prevalent conditions such as Alzheimer's disease, depression, and Parkinson's disease. Notable pathologies include dysfunctions of circadian rhythm, central metabolism, cardiovascular function, central stress responses, and movement mediated by the basal ganglia. Although evidence suggests exercise may benefit these conditions, the neurobiological mechanisms of exercise in specific brain regions involved in these important CNS functions have yet to be clarified. Here we review murine evidence about the effects of exercise on discrete brain regions involved in important CNS functions. Exercise effects on circadian rhythm, central metabolism, cardiovascular function, stress responses in the brain stem and hypothalamic pituitary axis, and movement are examined. The databases Pubmed, Web of Science, and Embase were searched for articles investigating regional brain adaptations to exercise. Brain regions examined included the brain stem, hypothalamus, and basal ganglia. We found evidence of multiple regional adaptations to both forced and voluntary exercise. Exercise can induce molecular adaptations in neuronal function in many instances. Taken together, these findings suggest that the regional physiological adaptations that occur with exercise could constitute a promising field for elucidating molecular and cellular mechanisms of recovery in psychiatric and neurological health conditions.

  18. 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...

  19. Advances in prehospital airway management.

    Science.gov (United States)

    Jacobs, Pe; Grabinsky, A

    2014-01-01

    Prehospital airway management is a key component of emergency responders and remains an important task of Emergency Medical Service (EMS) systems worldwide. The most advanced airway management techniques involving placement of oropharyngeal airways such as the Laryngeal Mask Airway or endotracheal tube. Endotracheal tube placement success is a common measure of out-of-hospital airway management quality. Regional variation in regard to training, education, and procedural exposure may be the major contributor to the findings in success and patient outcome. In studies demonstrating poor outcomes related to prehospital-attempted endotracheal intubation (ETI), both training and skill level of the provider are usually often low. Research supports a relationship between the number of intubation experiences and ETI success. National standards for certification of emergency medicine provider are in general too low to guarantee good success rate in emergency airway management by paramedics and physicians. Some paramedic training programs require more intense airway training above the national standard and some EMS systems in Europe staff their system with anesthesia providers instead. ETI remains the cornerstone of definitive prehospital airway management, However, ETI is not without risk and outcomes data remains controversial. Many systems may benefit from more input and guidance by the anesthesia department, which have higher volumes of airway management procedures and extensive training and experience not just with training of airway management but also with different airway management techniques and adjuncts.

  20. Nonpeptide tachykinin receptor antagonists. III. SB 235375, a low central nervous system-penetrant, potent and selective neurokinin-3 receptor antagonist, inhibits citric acid-induced cough and airways hyper-reactivity in guinea pigs.

    Science.gov (United States)

    Hay, Douglas W P; Giardina, Giuseppe A M; Griswold, Don E; Underwood, David C; Kotzer, Charles J; Bush, Brian; Potts, William; Sandhu, Punam; Lundberg, Dave; Foley, James J; Schmidt, Dulcie B; Martin, Lenox D; Kilian, David; Legos, Jeffrey J; Barone, Frank C; Luttmann, Mark A; Grugni, Mario; Raveglia, Luca F; Sarau, Henry M

    2002-01-01

    In this report the in vitro and in vivo pharmacological and pharmacokinetic profile of (-)-(S)-N-(alpha-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide (SB 235375), a low central nervous system (CNS)-penetrant, human neurokinin-3 (NK-3) receptor (hNK-3R) antagonist, is described. SB 235375 inhibited (125)I-[MePhe(7)]-neurokinin B (NKB) binding to membranes of Chinese hamster ovary (CHO) cells expressing the hNK-3R (CHO-hNK-3R) with a K(i) = 2.2 nM and antagonized competitively NKB-induced Ca(2+) mobilization in human embryonic kidney (HEK) 293 cells expressing the hNK-3R (HEK 293-hNK-3R) with a K(b) = 12 nM. SB 235375 antagonized senktide (NK-3R)-induced contractions in rabbit isolated iris sphincter (pA(2) = 8.1) and guinea pig ileal circular smooth muscles (pA(2) = 8.3). SB 235375 was selective for the hNK-3R compared with hNK-1 (K(i) > 100,000 nM) and hNK-2 receptors (K(i) = 209 nM), and was without effect, at 1 microM, in 68 other receptor, enzyme, and ion channel assays. Intravenous SB 235375 produced a dose-related inhibition of miosis induced by i.v. senktide in the rabbit (ED(50) of 0.56 mg/kg). Intraperitoneal SB 235375 (10-30 mg/kg) inhibited citric acid-induced cough and airways hyper-reactivity in guinea pigs. In mice oral SB 235375 (3-30 mg/kg) was without significant effect on the behavioral responses induced by intracerebral ventricular administration of senktide. Pharmacokinetic evaluation in the mouse and rat revealed that oral SB 235375 was well absorbed systemically but did not effectively cross the blood-brain barrier. The preclinical profile of SB 235375, encompassing high affinity, selectivity, oral activity, and low CNS penetration, suggests that it is an appropriate tool compound to define the pathophysiological roles of the NK-3Rs in the peripheral nervous system.

  1. Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

    OpenAIRE

    Carmody, Lisa A.; Zhao, Jiangchao; Patrick D. Schloss; Petrosino, Joseph F.; Murray, Susan; Young, Vincent B.; Jun Z Li; LiPuma, John J.

    2013-01-01

    Rationale: In persons with cystic fibrosis (CF), repeated exacerbations of pulmonary symptoms are associated with a progressive decline in lung function. Changes in the airway microbiota around the time of exacerbations are not well understood.

  2. Airway Clearance Devices for Cystic Fibrosis

    Science.gov (United States)

    2009-01-01

    Executive Summary Objective The purpose of this evidence-based analysis is to examine the safety and efficacy of airway clearance devices (ACDs) for cystic fibrosis and attempt to differentiate between devices, where possible, on grounds of clinical efficacy, quality of life, safety and/or patient preference. Background Cystic fibrosis (CF) is a common, inherited, life-limiting disease that affects multiple systems of the human body. Respiratory dysfunction is the primary complication and leading cause of death due to CF. CF causes abnormal mucus secretion in the airways, leading to airway obstruction and mucus plugging, which in turn can lead to bacterial infection and further mucous production. Over time, this almost cyclical process contributes to severe airway damage and loss of respiratory function. Removal of airway secretions, termed airway clearance, is thus an integral component of the management of CF. A variety of methods are available for airway clearance, some requiring mechanical devices, others physical manipulation of the body (e.g. physiotherapy). Conventional chest physiotherapy (CCPT), through the assistance of a caregiver, is the current standard of care for achieving airway clearance, particularly in young patients up to the ages of six or seven. CF patients are, however, living much longer now than in decades past. The median age of survival in Canada has risen to 37.0 years for the period of 1998-2002 (5-year window), up from 22.8 years for the 5-year window ending in 1977. The prevalence has also risen accordingly, last recorded as 3,453 in Canada in 2002, up from 1,630 in 1977. With individuals living longer, there is a greater need for independent methods of airway clearance. Airway Clearance Devices There are at least three classes of airway clearance devices: positive expiratory pressure devices (PEP), airway oscillating devices (AOD; either handheld or stationary) and high frequency chest compression (HFCC)/mechanical percussion (MP

  3. A Central Limit Theorem for the Zeroes of the Zeta Function

    CERN Document Server

    Rodgers, Brad

    2012-01-01

    On the assumption of the Riemann hypothesis, we generalize a central limit theorem of Fujii regarding the number of zeroes of Riemann's Zeta function that lie in a mesoscopic interval. The result mirrors results of Soshnikov and others in random matrix theory.

  4. Does Acupuncture Alter Pain-related Functional Connectivity of the Central Nervous System? A Systematic Review.

    Science.gov (United States)

    Villarreal Santiago, María; Tumilty, Steve; Mącznik, Aleksandra; Mani, Ramakrishnan

    2016-08-01

    Acupuncture has been studied for several decades to establish evidence-based clinical practice. This systematic review aims to evaluate evidence for the effectiveness of acupuncture in influencing the functional connectivity of the central nervous system in patients with musculoskeletal pain. A systematic search of the literature was conducted to identify studies in which the central response of acupuncture in patients with musculoskeletal pain was evaluated by neuroimaging techniques. Databases searched were AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PEDro, Pubmed, SCOPUS, SPORTDiscuss, and Web of Science. Included studies were assessed by two independent reviewers for their methodological quality by using the Downs and Black questionnaire and for their levels of completeness and transparency in reporting acupuncture interventions by using Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) criteria. Seven studies met the inclusion criteria. Three studies were randomized controlled trials (RCTs) and four studies were nonrandomized controlled trials (NRCTs). The neuroimaging techniques used were functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Positive effects on the functional connectivity of the central nervous system more consistently occurred during long-term acupuncture treatment. The results were heterogeneous from a descriptive perspective; however, the key findings support acupuncture's ability to alter pain-related functional connectivity in the central nervous system in patients with musculoskeletal pain.

  5. Microglia - insights into immune system structure, function, and reactivity in the central nervous system

    DEFF Research Database (Denmark)

    Wirenfeldt, Martin; Babcock, Alicia A; Vinters, Harry V

    2011-01-01

    Microglia are essential cellular components of a well-functioning central nervous system (CNS). The development and establishment of the microglial population differs from the other major cell populations in the CNS i.e. neurons and macroglia (astrocytes and oligodendrocytes). This different...

  6. CB2 receptors in the brain: role in central immune function

    OpenAIRE

    Cabral, G. A.; Raborn, E S; Griffin, L.; Dennis, J.; Marciano-Cabral, F

    2007-01-01

    Recently, it has been recognized that the cannabinoid receptor CB2 may play a functionally relevant role in the central nervous system (CNS). This role is mediated primarily through microglia, a resident population of cells in the CNS that is morphologically, phenotypically, and functionally related to macrophages. These cells also express the cannabinoid receptor CB1. The CB1 receptor (CB1R) is constitutively expressed at low levels while the CB2 receptor (CB2R) is expressed at higher levels...

  7. Functional diversity of Cercidiphyllum japonicum, communities in the Shennongjia Reserve, central China

    Institute of Scientific and Technical Information of China (English)

    Jintun Zhang; Bin Zhang; Zhiying Qian

    2015-01-01

    Functional diversity is significant to ecological processes of plant communities. We analyzed the variation of functional diversity of endangered species, Cercidi-phyllum japonicum, communities along an elevational gradient in the Shennongjia Reserve, central China. Sixty plots of 10 × 20 m from 1,350 to 2,050 m were set up and species composition, traits and environmental variables were measured and recorded. These data were analyzed using five functional diversity indices, functional attribute diversity, modified functional attribute diversity, plot based functional diversity, community based functional diversity and Rao’s functional diversity indices (Rao’s index), Functional diversities of C. japonicum communities were rich and varied greatly. Functional diversity declined non-linearly with increasing elevation. Functional diversity was significantly correlated with species richness and hetero-geneity. Elevation was a key environmental variable influencing functional diversity and species diversity. The five functional diversity indices were all effective for measuring functional diversity of communities. Functional diversity can be used as an indicator of conservation effi-ciency of endangered species such as C. japonicum.

  8. Loss of transforming growth factor-beta 2 leads to impairment of central synapse function

    Directory of Open Access Journals (Sweden)

    Rickmann Michael

    2008-10-01

    Full Text Available Abstract Background The formation of functional synapses is a crucial event in neuronal network formation, and with regard to regulation of breathing it is essential for life. Members of the transforming growth factor-beta (TGF-β superfamily act as intercellular signaling molecules during synaptogenesis of the neuromuscular junction of Drosophila and are involved in synaptic function of sensory neurons of Aplysia. Results Here we show that while TGF-β2 is not crucial for the morphology and function of the neuromuscular junction of the diaphragm muscle of mice, it is essential for proper synaptic function in the pre-Bötzinger complex, a central rhythm organizer located in the brainstem. Genetic deletion of TGF-β2 in mice strongly impaired both GABA/glycinergic and glutamatergic synaptic transmission in the pre-Bötzinger complex area, while numbers and morphology of central synapses of knock-out animals were indistinguishable from their wild-type littermates at embryonic day 18.5. Conclusion The results demonstrate that TGF-β2 influences synaptic function, rather than synaptogenesis, specifically at central synapses. The functional alterations in the respiratory center of the brain are probably the underlying cause of the perinatal death of the TGF-β2 knock-out mice.

  9. ORBITALES. A program for the calculation of wave functions with an analytical central potential; ORBITALES. Programa de calculo de Funciones de Onda para una Potencial Central Analitico

    Energy Technology Data Exchange (ETDEWEB)

    Yunta Carretero; Rodriguez Mayquez, E.

    1974-07-01

    In this paper is described the objective, basis, carrying out in FORTRAN language and use of the program ORBITALES. This program calculate atomic wave function in the case of ths analytical central potential (Author) 8 refs.

  10. Upper airway imaging and its role in preoperative airway evaluation

    Directory of Open Access Journals (Sweden)

    Jagadish G Sutagatti

    2016-01-01

    Full Text Available Ultrasonography (USG is well-known as a fast, safe, and noninvasive technique. Its application for imaging of the airway is now gaining momentum. The upper airway has a complex anatomy, and its assessment forms a vital part of every preanesthetic evaluation. Ultrasound (US imaging can help in upper airway assessment in the preoperative period. There are various approaches to upper airway USG. The technique has its own advantages, disadvantages, and limitations. This simple yet challenging imaging technique is all set to become an important part of routine preoperative airway evaluation. This article reviews the various approaches to upper airway US imaging, interpretation of the images, limitations, and disadvantages of the technique and its varied clinical applications in the preoperative period. The scientific material presented here was hand searched from textbooks and journals, electronically from PubMed, and Google scholar using text words.

  11. 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

    BACKGROUND AND OBJECTIVE: Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma......: Mean patient age was 67 years (confidence interval: 63-71) with a mean FEV1 of 78 % predicted (confidence interval: 70-85%). AHR correlated with sputum eosinophils (r = 0.68, P = 0.005) and eNO (r = 0.71, P ... or eNO. CONCLUSIONS: In older patients with asthma, airway inflammatory cells are linked to abnormal airway physiology. Eosinophilic airway inflammation is associated with AHR while neutrophilic inflammation may be an important determinant of airflow limitation at rest and airway closure during...

  12. A central analgesic mechanism of acupuncture for migraine An ongoing functional MRI study**

    Institute of Scientific and Technical Information of China (English)

    Lei Lan; Yujie Gao; Fang Zeng; Wei Qin; Mingkai Dong; Mailan Liu; Taipin Guo; Fanrong Liang

    2013-01-01

    Shaoyang acupoints are the most frequently used in migraine treatment. However, the central anal-gesic mechanism remains poorly understood. Studies have demonstrated that single stimulus of the verum acupuncture in healthy subjects can induce significant connectivity or activity changes in pain-related central networks compared with sham acupuncture. However, these findings are not indicative of the central analgesic mechanism of acupuncture at Shaoyang acupoints. Thus, we recruited 100 migraine sufferers and randomly assigned them into five groups: Shaoyang uncommon acupoint, Shaoyang common acupoint, Yangming uncommon acupoint, non-acupoint control, and blank control groups. Subjects were subjected to evaluation of curative effects and functional MRI prior to and after 10 and 20 acupuncture treatments. Al subjects were diagnosed by physicians and enrol ed fol owing clinical physical examination. Subjects were observed during 1-4 weeks after inclusion. At the fifth week, the first clinical evaluation and resting functional MRI were conducted. The Shaoyang uncom-mon acupoint, Shaoyang common acupoint, Yangming uncommon acupoint, and non-acupoint control grousp then were treated with acupuncture, five times per week, 20 times in total over 4 weeks. The second and third clinical evaluations and resting functional MRI screenings were conducted fol owing 10 and 20 acupuncture treatments. The blank control group was observed during the 5 to 8 week pe-riod, fol owed by clinical evaluation and resting functional MRI. The aim of this study was to examine changes in brain functional activity and central networks in subjects with migraine undergoing acu-puncture at Shaoyang uncommon acupoints. This study provides a further explanation of the central analgesic mechanism by which acupuncture at Shaoyang acupoints treats migraine.

  13. Functional organisation of central cardiovascular pathways: studies using c-fos gene expression.

    Science.gov (United States)

    Dampney, R A L; Horiuchi, J

    2003-12-01

    Until about 10 years ago, knowledge of the functional organisation of the central pathways that subserve cardiovascular responses to homeostatic challenges and other stressors was based almost entirely on studies in anaesthetised animals. More recently, however, many studies have used the method of the expression of immediate early genes, particularly the c-fos gene, to identify populations of central neurons that are activated by such challenges in conscious animals. In this review we first consider the advantages and limitations of this method. Then, we discuss how the application of the method of immediate early gene expression, when used alone or in combination with other methods, has contributed to our understanding of the central mechanisms that regulate the autonomic and neuroendocrine response to various cardiovascular challenges (e.g., hypotension, hypoxia, hypovolemia, and other stressors) as they operate in the conscious state. In general, the results of studies of central cardiovascular pathways using immediate early gene expression are consistent with previous studies in anaesthetised animals, but in addition have revealed other previously unrecognised pathways that also contribute to cardiovascular regulation. Finally, we briefly consider recent evidence indicating that immediate early gene expression can modify the functional properties of central cardiovascular neurons, and the possible significance of this in producing long-term changes in the regulation of the cardiovascular system both in normal and pathological conditions.

  14. Muscle fibers in the central nervous system of nemerteans: spatial organization and functional role.

    Science.gov (United States)

    Petrov, A A; Zaitseva, O V

    2012-08-01

    The system of muscle fibers associated with the brain and lateral nerve cords is present in all major groups of enoplan nemerteans. Unfortunately, very little is known about the functional role and spatial arrangement of these muscles of the central nervous system. This article examines the architecture of the musculature of the central nervous system in two species of monostiliferous nemerteans (Emplectonema gracile and Tetrastemma cf. candidum) using phalloidin staining and confocal microscopy. The article also briefly discusses the body-wall musculature and the muscles of the cephalic region. In both species, the lateral nerve cords possess two pairs of cardinal muscles that run the length of the nerve cords and pass through the ventral cerebral ganglia. A system of peripheral muscles forms a meshwork around the lateral nerve cords in E. gracile. The actin-rich processes that ramify within the nerve cords in E. gracile (transverse fibers) might represent a separate population of glia-like cells or sarcoplasmic projections of the peripheral muscles of the central nervous system. The lateral nerve cords in T. cf. candidum lack peripheral muscles but have muscles similar in their position and orientation to the transverse fibers. The musculature of the central nervous system is hypothesized to function as a support system for the lateral nerve cords and brain, preventing rupturing and herniation of the nervous tissue during locomotion. The occurrence of muscles of the central nervous system in nemerteans and other groups and their possible relevance in taxonomy are discussed.

  15. Coupled cellular therapy and magnetic targeting for airway regeneration.

    Science.gov (United States)

    Ordidge, Katherine L; Gregori, Maria; Kalber, Tammy L; Lythgoe, Mark F; Janes, Sam M; Giangreco, Adam

    2014-06-01

    Airway diseases including COPD (chronic obstructive pulmonary disease), cystic fibrosis and lung cancer are leading causes of worldwide morbidity and mortality, with annual healthcare costs of billions of pounds. True regeneration of damaged airways offers the possibility of restoring lung function and protecting against airway transformation. Recently, advances in tissue engineering have allowed the development of cadaveric and biosynthetic airway grafts. Although these have produced encouraging results, the ability to achieve long-term functional airway regeneration remains a major challenge. To promote regeneration, exogenously delivered stem and progenitor cells are being trialled as cellular therapies. Unfortunately, current evidence suggests that only small numbers of exogenously delivered stem cells engraft within lungs, thereby limiting their utility for airway repair. In other organ systems, magnetic targeting has shown promise for improving long-term robust cell engraftment. This technique involves in vitro cell expansion, magnetic actuation and magnetically guided cell engraftment to sites of tissue damage. In the present paper, we discuss the utility of coupling stem cell-mediated cellular therapy with magnetic targeting for improving airway regeneration.

  16. 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....... AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers)....

  17. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  18. IS SOCIAL RESPONSIBILITY CONSIDERS A FUNCTION OF LATIN AMERICAN CENTRAL BANKS?

    Directory of Open Access Journals (Sweden)

    Rosa Elena Carrera Pedroza

    2013-07-01

    Full Text Available The main purpose was to research whether social responsibility is considered a function of Latin American Central Banks. It focused on a qualitative and quantitative model, with epistemological base centered on phenomenology, a type of methodological approach that uses a feasible project and design field. From a statistical probabilistic procedure, a sample of nine Latin American Central banks was selected. For data collection, a questionnaire was applied, which revealed that 78% have education programs designed to train and disseminate economic knowledge, 56% takes social responsibility activities, while 44% makes grants to third parties.

  19. Airway Microbiota and the Implications of Dysbiosis in Asthma.

    Science.gov (United States)

    Durack, Juliana; Boushey, Homer A; Lynch, Susan V

    2016-07-01

    The mucosal surfaces of the human body are typically colonized by polymicrobial communities seeded in infancy and are continuously shaped by environmental exposures. These communities interact with the mucosal immune system to maintain homeostasis in health, but perturbations in their composition and function are associated with lower airway diseases, including asthma, a developmental and heterogeneous chronic disease with various degrees and types of airway inflammation. This review will summarize recent studies examining airway microbiota dysbioses associated with asthma and their relationship with the pathophysiology of this disease.

  20. Is the anesthesiologist actually prepared for loss of airway or respiratory function? A cross-sectional study conducted in a tertiary hospital

    Directory of Open Access Journals (Sweden)

    Helga Vasconcelos

    2014-02-01

    Full Text Available Objective To identify compliance with the procedures for securing the airway of patients submitted to anesthesia, defined as highly recommended in the World Health Organization Surgical Safety Checklist. Methods A prospective, cross-sectional, observational study was conducted with 87 patients aged 18 to 60 years, classified as ASA grade 1 or 2 according to the American Society of Anesthesiologists’ Physical Status Classification. The study variables consisted of: whether the Mallampati test had been performed, whether equipment was readily available for orotracheal intubation, whether the correct placement of the endotracheal tube was verified, whether patient ventilation was monitored and whether fasting was confirmed. Prevalence ratios and their respective 95% confidence intervals were calculated as measures of relative risk. Statistical significance was defined at 5%. Results It was found that in 87.4% of patients, the airway was not evaluated using the Mallampati classification and in 51.7% of cases, preoperative fasting was not confirmed. In 29.9% of cases, the ready availability of equipment for orotracheal intubation was not verified. In all of the cases in which the availability of this equipment was not checked, the patient was submitted to regional anesthesia, with a statistically significant difference compared to the cases in which the patient was submitted to general anesthesia. Conclusion Measures considered essential for the safety of the patient during surgery are still being ignored.

  1. Ultrasound of the airway

    Directory of Open Access Journals (Sweden)

    Pankaj Kundra

    2011-01-01

    Full Text Available Currently, the role of ultrasound (US in anaesthesia-related airway assessment and procedural interventions is encouraging, though it is still ill defined. US can visualise anatomical structures in the supraglottic, glottic and subglottic regions. The floor of the mouth can be visualised by both transcutaneous view of the neck and also by transoral or sublinguial views. However, imaging the epiglottis can be challenging as it is suspended in air. US may detect signs suggestive of difficult intubation, but the data are limited. Other possible applications in airway management include confirmation of correct endotracheal tube placement, prediction of post-extubation stridor, evaluation of soft tissue masses in the neck prior to intubation, assessment of subglottic diameter for determination of paediatric endotracheal tube size and percutaneous dilatational tracheostomy. With development of better probes, high-resolution imaging, real-time picture and clinical experience, US has become the potential first-line noninvasive airway assessment tool in anaesthesia and intensive care practice.

  2. 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.

  3. Airway epithelium is a predominant source of endogenous airway GABA and contributes to relaxation of airway smooth muscle tone

    OpenAIRE

    Gallos, George; Townsend, Elizabeth; Yim, Peter; Virag, Laszlo; Zhang, Yi; Xu, Dingbang; Bacchetta, Matthew; Emala, Charles W.

    2012-01-01

    Chronic obstructive pulmonary disease and asthma are characterized by hyperreactive airway responses that predispose patients to episodes of acute airway constriction. Recent studies suggest a complex paradigm of GABAergic signaling in airways that involves GABA-mediated relaxation of airway smooth muscle. However, the cellular source of airway GABA and mechanisms regulating its release remain unknown. We questioned whether epithelium is a major source of GABA in the airway and whether the ab...

  4. Early diagnosis of asthma in young children by using non-invasive biomarkers of airway inflammation and early lung function measurements: study protocol of a case-control study

    Directory of Open Access Journals (Sweden)

    Jöbsis Quirijn

    2009-06-01

    Full Text Available Abstract Background Asthma is the most common chronic disease in childhood, characterized by chronic airway inflammation. There are problems with the diagnosis of asthma in young children since the majority of the children with recurrent asthma-like symptoms is symptom free at 6 years, and does not have asthma. With the conventional diagnostic tools it is not possible to differentiate between preschool children with transient symptoms and children with asthma. The analysis of biomarkers of airway inflammation in exhaled breath is a non-invasive and promising technique to diagnose asthma and monitor inflammation in young children. Moreover, relatively new lung function tests (airway resistance using the interrupter technique have become available for young children. The primary objective of the ADEM study (Asthma DEtection and Monitoring study, is to develop a non-invasive instrument for an early asthma diagnosis in young children, using exhaled inflammatory markers and early lung function measurements. In addition, aetiological factors, including gene polymorphisms and gene expression profiles, in relation to the development of asthma are studied. Methods/design A prospective case-control study is started in 200 children with recurrent respiratory symptoms and 50 control subjects without respiratory symptoms. At 6 years, a definite diagnosis of asthma is made (primary outcome measure on basis of lung function assessments and current respiratory symptoms ('golden standard'. From inclusion until the definite asthma diagnosis, repeated measurements of lung function tests and inflammatory markers in exhaled breath (condensate, blood and faeces are performed. The study is registered and ethically approved. Discussion This article describes the study protocol of the ADEM study. The new diagnostic techniques applied in this study could make an early diagnosis of asthma possible. An early and reliable asthma diagnosis at 2–3 years will have

  5. Human airway xenograft models of epithelial cell regeneration

    Directory of Open Access Journals (Sweden)

    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.

  6. How Can 1+1=3? beta(2)-Adrenergic and Glucocorticoid Receptor Agonist Synergism in Obstructive Airway Diseases

    NARCIS (Netherlands)

    Schmidt, Martina; Michel, Martin C.

    2011-01-01

    For a long time it was believed that beta(2)-adrenergic receptor agonists used in the treatment of obstructive airway diseases worked primarily on airway smooth muscle cells, causing relaxation, whereas glucocorticoids primarily improved airway function via their anti-inflammatory action, indicating

  7. Systems physiology of the airways in health and obstructive pulmonary disease.

    Science.gov (United States)

    Bates, Jason H T

    2016-09-01

    Fresh air entering the mouth and nose is brought to the blood-gas barrier in the lungs by a repetitively branching network of airways. Provided the individual airway branches remain patent, this airway tree achieves an enormous amplification in cross-sectional area from the trachea to the terminal bronchioles. Obstructive lung diseases such as asthma occur when airway patency becomes compromised. Understanding the pathophysiology of these obstructive diseases thus begins with a consideration of the factors that determine the caliber of an individual airway, which include the force balance between the inward elastic recoil of the airway wall, the outward tethering forces of its parenchymal attachments, and any additional forces due to contraction of airway smooth muscle. Other factors may also contribute significantly to airway narrowing, such as thickening of the airway wall and accumulation of secretions in the lumen. Airway obstruction becomes particularly severe when these various factors occur in concert. However, the effect of airway abnormalities on lung function cannot be fully understood only in terms of what happens to a single airway because narrowing throughout the airway tree is invariably heterogeneous and interdependent. Obstructive lung pathologies thus manifest as emergent phenomena arising from the way in which the airway tree behaves a system. These emergent phenomena are studied with clinical measurements of lung function made by spirometry and by mechanical impedance measured with the forced oscillation technique. Anatomically based computational models are linking these measurements to underlying anatomic structure in systems physiology terms. WIREs Syst Biol Med 2016, 8:423-437. doi: 10.1002/wsbm.1347 For further resources related to this article, please visit the WIREs website.

  8. Pharmacology of airway smooth muscle proliferation

    NARCIS (Netherlands)

    Gosens, Reinoud; Roscioni, Sara S.; Dekkers, Bart G. J.; Pera, Tonio; Schmidt, Martina; Schaafsma, Dedmer; Zaagsma, Johan; Meurs, Herman

    2008-01-01

    Airway smooth muscle thickening is a pathological feature that contributes significantly to airflow limitation and airway hyperresponsiveness in asthma. Ongoing research efforts aimed at identifying the mechanisms responsible for the increased airway smooth muscle mass have indicated that hyperplasi

  9. Integrin αVβ5 Mediated TGF-β Activation by Airway Smooth Muscle Cells in Asthma

    OpenAIRE

    Tatler, Amanda L; John, Alison E.; Jolly, Lisa; Habgood, Anthony; Porte, Jo; Brightling, Chris; Knox, Alan J; Pang, Linhua; Sheppard, Dean; Huang, Xiaozhu; Jenkins, Gisli

    2011-01-01

    Severe asthma is associated with airway remodelling, characterised by structural changes including increased smooth muscle mass and matrix deposition in the airway, leading to deteriorating lung function. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine leading to increased synthesis of matrix molecules by human airway smooth muscle cells (HASMs) and is implicated in asthmatic airway remodelling. TGF-β is synthesised as a latent complex, sequestered in the extracellular matrix, ...

  10. Functional Neuronavigation: Comparison of spatial congruence between fMRI and electrocortical stimulation in central region tumor surgery

    OpenAIRE

    Wachter, Dorothee

    2010-01-01

    Background: The surgical treatment of lesions in or around the central region confronts the neurosurgeon with a great challenge. Radical tumor resection leads to a better outcome but it also bears the risk of postoperative neurological deficit due to the functional importance of the central region. Throughout the last couple of years different techniques made it possible to identify the patient’s specific functional and anatomical topography. The central sulcus and the adjacent gyri...

  11. A review of nanoparticle functionality and toxicity on the central nervous system

    OpenAIRE

    Yang, Z.; Z. W. Liu; Allaker, R P; Reip, P.; Oxford, J; Ahmad, Z.; Ren, G.

    2010-01-01

    Although nanoparticles have tremendous potential for a host of applications, their adverse effects on living cells have raised serious concerns recently for their use in the healthcare and consumer sectors. As regards the central nervous system (CNS), research data on nanoparticle interaction with neurons has provided evidence of both negative and positive effects. Maximal application dosage of nanoparticles in materials to provide applications such as antibacterial and antiviral functions is...

  12. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

    Science.gov (United States)

    Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

    2015-05-29

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia.

  13. A Robust Function to Return the Cumulative Density of Non-Central F Distributions in Microsoft Office Excel

    Science.gov (United States)

    Nelson, James Byron

    2016-01-01

    The manuscript presents a Visual Basic[superscript R] for Applications function that operates within Microsoft Office Excel[superscript R] to return the area below the curve for a given F within a specified non-central F distribution. The function will be of use to Excel users without programming experience wherever a non-central F distribution is…

  14. [Effects of once-daily low-dose administration of sustained-release theophylline on airway inflammation and airway hyperresponsiveness in patients with asthma].

    Science.gov (United States)

    Terao, Ichiro

    2002-04-01

    Bronchial asthma is eosinophilic airway inflammation with enhanced airway responsiveness induced by eosinophilic granule proteins such as eosinophilic cationic protein (ECP) that are released from eosinophils. In the present study using 30 outpatients with mild to moderate asthma who had no history of treatment with steroid inhalation, we examined the effects of 4-week low-dose (200 mg/day) treatment with Uniphyl Tablets, a sustained-release theophylline formulated for once-daily dosing, on airway inflammation and airway hyperresponsiveness, as well as on respiratory function. Uniphyl Tablets significantly (p statistically significant (p V50 also showed statistically significant (p < 0.05) improvement. Mean blood theophylline concentration at the time the improvements were seen was 3.95 mg/mL. These results suggest that low-dose administration of Uniphyl Tablets has anti-airway inflammatory and anti-airway hyperresponsiveness effects in mild to moderate asthmatic patients.

  15. Inhalation of Hydrocarbon Jet Fuel Suppress Central Auditory Nervous System Function.

    Science.gov (United States)

    Guthrie, O'neil W; Wong, Brian A; McInturf, Shawn M; Reboulet, James E; Ortiz, Pedro A; Mattie, David R

    2015-01-01

    More than 800 million L/d of hydrocarbon fuels is used to power cars, boats, and jet airplanes. The weekly consumption of these fuels necessarily puts the public at risk for repeated inhalation exposure. Recent studies showed that exposure to hydrocarbon jet fuel produces lethality in presynaptic sensory cells, leading to hearing loss, especially in the presence of noise. However, the effects of hydrocarbon jet fuel on the central auditory nervous system (CANS) have not received much attention. It is important to investigate the effects of hydrocarbons on the CANS in order to complete current knowledge regarding the ototoxic profile of such exposures. The objective of the current study was to determine whether inhalation exposure to hydrocarbon jet fuel might affect the functions of the CANS. Male Fischer 344 rats were randomly divided into four groups (control, noise, fuel, and fuel + noise). The structural and functional integrity of presynaptic sensory cells was determined in each group. Neurotransmission in both peripheral and central auditory pathways was simultaneously evaluated in order to identify and differentiate between peripheral and central dysfunctions. There were no detectable effects on pre- and postsynaptic peripheral functions. However, the responsiveness of the brain was significantly depressed and neural transmission time was markedly delayed. The development of CANS dysfunctions in the general public and the military due to cumulative exposure to hydrocarbon fuels may represent a significant but currently unrecognized public health issue.

  16. Ecological Function Value of Tropical Forests in the Central Mountainous Areas of Hainan Island

    Institute of Scientific and Technical Information of China (English)

    Jing; GAO; Zuguang; ZHOU

    2013-01-01

    The integrated value of the ecological function of tropical forests in the central mountainous areas of Hainan Island was 33.064 8 billion yuan/a in 2010(soil improvement,soil consolidation,soil nutrient maintenance,water storage and moisture regulation,water purification,carbon sequestration,oxygen releasing,air purification,biodiversity conservation,eco-tourism),equivalent to 16.1%of GDP in Hainan Province this year(205.212 billion yuan).The tropical forests in the central mountainous areas of Hainan Island make great contribution to Hainan Island’s ecology,and play an important role in maintaining the stability of the ecological environment in Hainan Island.Through the understanding of major ecological function value of tropical forests,it is necessary to make people cherish the tropical forests in the central ecological function conservation areas of Hainan Province,and spontaneously throw themselves into the ecological environment protection and construction,to promote the rapid and sustainable development of construction in Hainan Province as an international tourism island.

  17. Central African biomes and forest succession stages derived from modern pollen data and plant functional types

    Directory of Open Access Journals (Sweden)

    J. Lebamba

    2009-07-01

    Full Text Available New detailed vegetation reconstructions are proposed in Atlantic Central Africa from a modern pollen data set derived from 199 sites (Cameroon, Gabon and Congo including 131 new sites. In this study, the concept of plant functional classification is improved with new and more detailed plant functional types (PFTs and new aggregations of pollen taxa. Using the biomisation method, we reconstructed (1 modern potential biomes and (2 potential succession stages of forest regeneration, a new approach in Atlantic Central African vegetation dynamics and ecosystem functioning reconstruction. When compared to local vegetation, potential biomes are correctly reconstructed (97.5% of the sites and tropical rain forest (TRFO biome is well identified from tropical seasonal forest (TSFO biome. When the potential biomes are superimposed on the White's vegetation map, only 76.4% of the sites are correctly reconstructed. But using botanical data, correspondence and cluster analyses, the 43 sites from Congo (Mayombe evidence more affinities with those of central Gabon and so they can also be considered as correctly reconstructed as TRFO biome and White's map should be revised. In terms of potential succession stages of forest regeneration, the mature forest (TMFO is well differentiated from the secondary forest (TSFE, but inside this latter group, the young and the pioneer stages are not clearly identified due probably to their low sampling representation. Moreover, linked to their progressive and mosaic character, the boundaries between two forest biomes or two forest stages are not clearly detected and need also a more intensive sampling in such transitions.

  18. Gingival hyperplasia by upper airway obstruction

    OpenAIRE

    Díaz Soriano, Ana; Docente Departamento Académico de Estomatología Biosocial.; Lévano Torres, Víctor; Docente Departamento Académico Médico Quirúrgico.; Pastor Yataco, Shamila; Alumnos del 3er año de Odontología de la UNMSM.; Vallejos Pulido, Arturo; Alumnos del 3er año de Odontología de la UNMSM.; Huamanyauri Gonzales, Lizbeth; Alumnos del 3er año de Odontología de la UNMSM.

    2014-01-01

    The effects of mouth breathing are the introduction of cold air, dry and dusty in the mouth and pharynx, the lost functions of heating, humedificacion and filtering the air entering the nose increases the oral mucosa irritation and pharyngeal. A case of a female patient 15 years old who comes for consultation of Periodontology with increase in volume and gingival redness in the upper anterior sector of upper airway obstruction caused by deviated septum right turbinate hypertrophy and maxillar...

  19. Small particles disrupt postnatal airway development

    OpenAIRE

    2010-01-01

    Increasing numbers of epidemiologic studies associate air pollution exposure in children with decreased lung function development. The objective of this study was to examine the effects of exposure to combustion-generated fine [230 and 212 nm number mean aerodynamic particle diameter (NMAD)] to ultrafine (73 nm NMAD) particles differing in elemental (EC) and organic (OC) carbon content on postnatal airway development in rats. Neonatal Sprague-Dawley rats were exposed from postnatal day 7 thro...

  20. Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience

    Directory of Open Access Journals (Sweden)

    Diankun Gong

    2016-01-01

    Full Text Available Action video games (AVGs have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN and Central Executive Network (CEN, which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts’ and amateurs’ resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity.

  1. Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience.

    Science.gov (United States)

    Gong, Diankun; He, Hui; Ma, Weiyi; Liu, Dongbo; Huang, Mengting; Dong, Li; Gong, Jinnan; Li, Jianfu; Luo, Cheng; Yao, Dezhong

    2016-01-01

    Action video games (AVGs) have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN) and Central Executive Network (CEN), which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts' and amateurs' resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity.

  2. Muscle Strength, Physical Activity, and Functional Limitations in Older Adults with Central Obesity

    Directory of Open Access Journals (Sweden)

    Cassandra M. Germain

    2016-01-01

    Full Text Available Background. Obesity and muscle weakness are independently associated with increased risk of physical and functional impairment in older adults. It is unknown whether physical activity (PA and muscle strength combined provide added protection against functional impairment. This study examines the association between muscle strength, PA, and functional outcomes in older adults with central obesity. Methods. Prevalence and odds of physical (PL, ADL, and IADL limitation were calculated for 6,388 community dwelling adults aged ≥ 60 with central obesity. Individuals were stratified by sex-specific hand grip tertiles and PA. Logistic models were adjusted for age, education, comorbidities, and body-mass index and weighted. Results. Overall prevalence of PL and ADL and IADL limitations were progressively lower by grip category. Within grip categories, prevalence was lower for individuals who were active than those who were inactive. Adjusted models showed significantly lower odds of PL OR 0.42 [0.31, 0.56]; ADL OR 0.60 [0.43, 0.84], and IADL OR 0.46 [0.35, 0.61] for those in the highest grip strength category as compared to those in the lowest grip category. Conclusion. Improving grip strength in obese elders who are not able to engage in traditional exercise is important for reducing odds of physical and functional impairment.

  3. Green's Function of a General PT-Symmetric Non-Hermitian Non-central Potential

    CERN Document Server

    Mourya, Brijesh Kumar

    2016-01-01

    We study the path integral solution of a system of particle moving in certain class of PT symmetric non-Hermitian and non-central potential. The Hamil- tonian of the system is converted to a separable Hamiltonian of Liouville type in parabolic coordinates and is further mapped into a Hamiltonian corresponding to two 2-dimensional simple harmonic oscillators (SHOs). Thus the explicit Green's functions for a general non-central PT symmetric non hermitian potential are cal- culated in terms of that of 2d SHOs. The entire spectrum for this three dimensional system is shown to be always real leading to the fact that the system remains in unbroken PT phase all the time.

  4. Obesity and obstructive sleep apnoea: mechanisms for increased collapsibility of the passive pharyngeal airway.

    Science.gov (United States)

    Isono, Shiroh

    2012-01-01

    Epidemiological evidence suggests there are significant links between obesity and obstructive sleep apnoea (OSA), with a particular emphasis on the importance of fat distribution in the development of OSA. In patients with OSA, the structure of the pharyngeal airway collapses. A collapsible tube within a rigid box collapses either due to decreased intraluminal pressure or increased external tissue pressure (i.e. reduction in transmural pressure), or due to reduction in the longitudinal tension of the tube. Accordingly, obesity should structurally increase the collapsibility of the pharyngeal airway due to excessive fat deposition at two distinct locations. In the pharyngeal airway region, excessive soft tissue for a given maxillomandibular enclosure size (upper airway anatomical imbalance) can increase tissue pressure surrounding the pharyngeal airway, thereby narrowing the airway. Even mild obesity may cause anatomical imbalance in individuals with a small maxilla and mandible. Lung volume reduction due to excessive central fat deposition may decrease longitudinal tracheal traction forces and pharyngeal wall tension, changing the 'tube law' in the pharyngeal airway (lung volume dependence of the upper airway). The lung volume dependence of pharyngeal airway patency appears to contribute more significantly to the development of OSA in morbidly obese, apnoeic patients. Neurostructural interactions required for stable breathing may be influenced by obesity-related hormones and cytokines. Accumulating evidence strongly supports these speculations, but further intensive research is needed.

  5. 高频电刀氩气刀治疗伴呼吸功能不全的大气道肿瘤效果和安全性%Efficacy and safety of electrocautery and argon plasma coagulation for the therapy of central airway tumor with respiratory insufficiency

    Institute of Scientific and Technical Information of China (English)

    周一平; 陈小可; 刘慧; 夏莉萍; 喻海琼; 刘念; 李爱芬; 林海容

    2015-01-01

    目的:探讨经支气管镜高频电刀氩气刀治疗伴呼吸功能不全大气道肿瘤的有效性和安全性。方法分析广东医学院附属福田医院2010年9月~2014年12月19例经病理确诊的伴呼吸功能不全的晚期中央型肺癌患者的高频电刀氩气刀治疗情况。结果19例患者共进行了37次治疗,手术室全麻6人6次,其他31次均在支气管镜室非全麻下手术,25次辅助通气下进行。有效8例,部分有效7例,轻度有效3例。同时进行光动力照射治疗的有6例,置入金属支架的有1例。结论治疗大气道肿瘤伴呼吸功能不全,选择良好的麻醉和呼吸支持方式后,高频电刀氩气刀术是一种安全、有效的方法。%Objective To investigate the efficacy and safety of electrocautery and argon plasma coagulation (APC) for the therapy of central airway tumor with respiratory insufficiency. Methods The efficacy of electrocautery and APC for the therapy of 19 pathologically confirmed advanced central airway tumor with respiratory insufficiency from September 2010 to December 2014 in Affiliated Futian Hospital of Guangdong Medical College was analyzed. Results Of the 19 patients with a total of 37 treatments, 6 patients and 6 periods were in the operating room under general anesthesia;the other 31 periods were in the bronchoscopy room under potical anesthesia with sedation, 25 periods with assisted me-chanical ventilation. 8 cases were effective, 7 cases were partial response, 3 cases were mild effective. 6 cases took si-multaneous photodynamic therapy, one case took metal stent implantation. Conclusion With the proper anesthesia and respiratory support, electrocautery and APC is a safe and effective method for central airway tumor with respiratory in-sufficiency.

  6. Germinal Center Formation and Local Immunoglobulin E (IgE) Production in the Lung after an Airway Antigenic Challenge

    OpenAIRE

    1996-01-01

    Airway inflammation plays a central role in the pathogenesis of asthma. However, the precise contribution of all cell types in the development and maintenance of airway hyperreactivity and histopathology during allergic inflammation remains unclear. After sensitization of mice in the periphery, challenge by multiple intratracheal (i.t.) instillations of ovalbumin (OVA) results in eosinophilia, mononuclear cell infiltration, and airway epithelial changes analogous to that seen in asthma (Blyth...

  7. Mechanically patterning the embryonic airway epithelium

    Science.gov (United States)

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  8. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

    Directory of Open Access Journals (Sweden)

    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  9. Understanding the Functional Central Limit Theorems with Some Applications to Unit Root Testing with Structural Change

    Directory of Open Access Journals (Sweden)

    Juan Carlos Aquino

    2013-06-01

    Full Text Available The application of different unit root statistics is by now a standard practice in empirical work. Even when it is a practical issue, these statistics have complex nonstandard distributions depending on functionals of certain stochastic processes, and their derivations represent a barrier even for many theoretical econometricians. These derivations are based on rigorous and fundamental statistical tools which are not (very well known by standard econometricians. This paper aims to fill this gap by explaining in a simple way one of these fundamental tools: namely, the Functional Central Limit Theorem. To this end, this paper analyzes the foundations and applicability of two versions of the Functional Central Limit Theorem within the framework of a unit root with a structural break. Initial attention is focused on the probabilistic structure of the time series to be considered. Thereafter, attention is focused on the asymptotic theory for nonstationary time series proposed by Phillips (1987a, which is applied by Perron (1989 to study the effects of an (assumed exogenous structural break on the power of the augmented Dickey-Fuller test and by Zivot and Andrews (1992 to criticize the exogeneity assumption and propose a method for estimating an endogenous breakpoint. A systematic method for dealing with efficiency issues is introduced by Perron and Rodriguez (2003, which extends the Generalized Least Squares detrending approach due to Elliot et al. (1996. An empirical application is provided.

  10. Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

    Lo, P.; Sporring, J.; Ashraf, H.;

    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 differentiate between airway and non-airway voxels. This is in contrast to previous works that use either intensity alone or hand crafted models of airway appearance. We show that the appearance model can be trained with a set of easily acquired, incomplete, airway tree segmentations. A vessel orientation...

  11. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions.

    Science.gov (United States)

    Browning, Kirsteen N; Travagli, R Alberto

    2014-10-01

    Although the gastrointestinal (GI) tract possesses intrinsic neural plexuses that allow a significant degree of autonomy over GI functions, the central nervous system (CNS) provides extrinsic neural inputs that regulate, modulate, and control these functions. While the intestines are capable of functioning in the absence of extrinsic inputs, the stomach and esophagus are much more dependent upon extrinsic neural inputs, particularly from parasympathetic and sympathetic pathways. The sympathetic nervous system exerts a predominantly inhibitory effect upon GI muscle and provides a tonic inhibitory influence over mucosal secretion while, at the same time, regulates GI blood flow via neurally mediated vasoconstriction. The parasympathetic nervous system, in contrast, exerts both excitatory and inhibitory control over gastric and intestinal tone and motility. Although GI functions are controlled by the autonomic nervous system and occur, by and large, independently of conscious perception, it is clear that the higher CNS centers influence homeostatic control as well as cognitive and behavioral functions. This review will describe the basic neural circuitry of extrinsic inputs to the GI tract as well as the major CNS nuclei that innervate and modulate the activity of these pathways. The role of CNS-centered reflexes in the regulation of GI functions will be discussed as will modulation of these reflexes under both physiological and pathophysiological conditions. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide these answers.

  12. Airway complications after lung transplantation.

    Science.gov (United States)

    Machuzak, Michael; Santacruz, Jose F; Gildea, Thomas; Murthy, Sudish C

    2015-01-01

    Airway complications after lung transplantation present a formidable challenge to the lung transplant team, ranging from mere unusual images to fatal events. The exact incidence of complications is wide-ranging depending on the type of event, and there is still evolution of a universal characterization of the airway findings. Management is also wide-ranging. Simple observation or simple balloon bronchoplasty is sufficient in many cases, but vigilance following more severe necrosis is required for late development of both anastomotic and nonanastomotic airway strictures. Furthermore, the impact of coexisting infection, rejection, and medical disease associated with high-level immunosuppression further complicates care.

  13. Central nervous system action of peptides to influence gastrointestinal motor function.

    Science.gov (United States)

    Taché, Y; Garrick, T; Raybould, H

    1990-02-01

    The central action of peptides to influence GI motility in experimental animals is summarized in Table 1. TRH stimulates gastric, intestinal, and colonic contractility in rats and in several experimental species. A number of peptides including calcitonin, CGRP, neurotensin, NPY, and mu opioid peptides act centrally to induce a fasted MMC pattern of intestinal motility in fed animals while GRF and substance P shorten its duration. The dorsal vagal complex is site of action for TRH-, bombesin-, and somatostatin-induced stimulation of gastric contractility, and for CCK-, oxytocin- and substance P-induced decrease in gastric contractions or intraluminal pressure. The mechanisms through which TRH, bombesin, calcitonin, neurotensin, CCK, and oxytocin alter GI motility are vagally mediated. An involvement of central peptidergic neurons in the regulation of gut motility has recently been demonstrated in Aplysia, indicating that such regulatory mechanisms are important in the phylogenesis. Alterations of the pattern of GI motor activity are associated with functional changes in transit. TRH is so far the only centrally acting peptide stimulating simultaneously gastric, intestinal, and colonic transit in various animals species. Opioid peptides acting on mu receptor subtypes in the brain exert the opposite effect and inhibit concomitantly gastric, intestinal, and colonic transit. Bombesin and CRF were found to act centrally to inhibit gastric and intestinal transit and to stimulate colonic transit in the rat. The antitransit effect of calcitonin and CGRP is limited to the stomach and small intestine. The delay in GI transit is associated with reduced GI contractility for most of the peptides except central bombesin that increases GI motility. Nothing is known about brain sites through which these peptides act to alter gastric emptying and colonic transit. Regarding brain sites influencing intestinal transit, TRH-induced stimulation of intestinal transit in the rat is

  14. Biological oscillations for learning walking coordination: dynamic recurrent neural network functionally models physiological central pattern generator.

    Science.gov (United States)

    Hoellinger, Thomas; Petieau, Mathieu; Duvinage, Matthieu; Castermans, Thierry; Seetharaman, Karthik; Cebolla, Ana-Maria; Bengoetxea, Ana; Ivanenko, Yuri; Dan, Bernard; Cheron, Guy

    2013-01-01

    The existence of dedicated neuronal modules such as those organized in the cerebral cortex, thalamus, basal ganglia, cerebellum, or spinal cord raises the question of how these functional modules are coordinated for appropriate motor behavior. Study of human locomotion offers an interesting field for addressing this central question. The coordination of the elevation of the 3 leg segments under a planar covariation rule (Borghese et al., 1996) was recently modeled (Barliya et al., 2009) by phase-adjusted simple oscillators shedding new light on the understanding of the central pattern generator (CPG) processing relevant oscillation signals. We describe the use of a dynamic recurrent neural network (DRNN) mimicking the natural oscillatory behavior of human locomotion for reproducing the planar covariation rule in both legs at different walking speeds. Neural network learning was based on sinusoid signals integrating frequency and amplitude features of the first three harmonics of the sagittal elevation angles of the thigh, shank, and foot of each lower limb. We verified the biological plausibility of the neural networks. Best results were obtained with oscillations extracted from the first three harmonics in comparison to oscillations outside the harmonic frequency peaks. Physiological replication steadily increased with the number of neuronal units from 1 to 80, where similarity index reached 0.99. Analysis of synaptic weighting showed that the proportion of inhibitory connections consistently increased with the number of neuronal units in the DRNN. This emerging property in the artificial neural networks resonates with recent advances in neurophysiology of inhibitory neurons that are involved in central nervous system oscillatory activities. The main message of this study is that this type of DRNN may offer a useful model of physiological central pattern generator for gaining insights in basic research and developing clinical applications.

  15. Biological oscillations for learning walking coordination: dynamic recurrent neural network functionally models physiological central pattern generator

    Directory of Open Access Journals (Sweden)

    Thomas eHoellinger

    2013-05-01

    Full Text Available The existence of dedicated neuronal modules such as those organized in the cerebral cortex, thalamus, basal ganglia, cerebellum or spinal cord raises the question of how these functional modules are coordinated for appropriate motor behavior. Study of human locomotion offers an interesting field for addressing this central question. The coordination of the elevation of the 3 leg segments under a planar covariation rule (Borghese et al., 1996 was recently modeled (Barliya et al., 2009 by phase-adjusted simple oscillators shedding new light on the understanding of the central pattern generator processing relevant oscillation signals. We describe the use of a dynamic recurrent neural network (DRNN mimicking the natural oscillatory behavior of human locomotion for reproducing the planar covariation rule in both legs at different walking speeds. Neural network learning was based on sinusoid signals integrating frequency and amplitude features of the first three harmonics of the sagittal elevation angles of the thigh, shank and foot of each lower limb. We verified the biological plausibility of the neural networks. Best results were obtained with oscillations extracted from the first three harmonics in comparison to oscillations outside the harmonic frequency peaks. Physiological replication steadily increased with the number of neuronal units from 1 to 80, where similarity index reached 0.99. Analysis of synaptic weighting showed that the proportion of inhibitory connections consistently increased with the number of neuronal units in the DRNN. This emerging property in the artificial neural networks resonates with recent advances in neurophysiology of inhibitory neurons that are involved in central nervous system oscillatory activities. The main message of this study is that this type of DRNN may offer a useful model of physiological central pattern generator for gaining insights in basic research and developing clinical applications.

  16. Airway Epithelium Stimulates Smooth Muscle Proliferation

    OpenAIRE

    Malavia, Nikita K.; Raub, Christopher B.; Mahon, Sari B.; Brenner, Matthew; Reynold A Panettieri; George, Steven C.

    2009-01-01

    Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air–liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (...

  17. Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome.

    Science.gov (United States)

    Carneiro, Gláucia; Togeiro, Sônia Maria; Hayashi, Lílian F; Ribeiro-Filho, Fernando Flexa; Ribeiro, Artur Beltrame; Tufik, Sérgio; Zanella, Maria Teresa

    2008-08-01

    Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. The aim of this study was to evaluate HPA axis and ambulatory blood pressure monitoring in obese men with and without OSAS and to determine whether nasal continuous positive airway pressure therapy (nCPAP) influenced responses. Twenty-four-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 16 obese men with OSAS and 13 obese men controls. Nine men with severe apnea were reevaluated 3 mo after nCPAP therapy. Body mass index and blood pressure of OSAS patients and obese controls were similar. In OSAS patients, the percentage of fall in systolic blood pressure at night (P = 0.027) and salivary cortisol suppression postdexamethasone (P = 0.038) were lower, whereas heart rate (P = 0.022) was higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (P = 0.036) and a greater cortisol suppression after dexamethasone (P = 0.001). No difference in arterial blood pressure (P = 0.183) was observed after 3 mo of nCPAP therapy. Improvement in cortisol suppression was positively correlated with an improvement in apnea-hypopnea index during nCPAP therapy (r = 0.799, P = 0.010). In conclusion, men with OSAS present increased postdexamethasone cortisol levels and heart rate, which were recovered by nCPAP.

  18. Cardiac biopotentials influence on central nervous system functioning: first steps in hypothesis verification

    Directory of Open Access Journals (Sweden)

    Kondal'skaya Yu.O.

    2012-12-01

    Full Text Available The research goal is to verify the hypothesis on influence of cardiac biopotentials on central nervous system. Materials: 20 healthy individuals aged 18-26 years old have been participated in the investigations. Two groups composed of 10 patients each have been formed. Double increase in heart biopotentials by means of artificial impulse insertion between natural cardiac contractions has been modeled. Artificial impulses have been similar to unaffected ones, produced in a normal heart work. Additional impulses have been generated using external pacemaker and have been linked up with electrodes on the chest. They have been synchronized with the heart rhythm and located in-between R waves. The duration of those impulses has been fully matched to ventricular complex. Their amplitude has been adjusted individually depending on the height of R wave. Nervous system mobility has been used as the indicator reflecting the central nervous system functioning. Degree of mobility has been defined on the basis of tapping test results. The test has been repeated at specific intervals. Groups have been exposed to two adverse testing modes. Additional impulses have been conducted to the patients of group I within an hour over a period of the first and the third 15-minute intervals and to the patients of group II over a period of the second and the fourth 15-minute intervals. In the middle and in the end of each time interval tapping test has been carried out. After preliminary analysis two other modes of stimulation have been tested. The stimulation has been performed within the 40-minute course: over a period of the first 20-minute interval and vice versa. Results: Detailed evaluation has revealed that short-time increase of nervous processes has been checked in combination with decrease in their stability. Conclusion: The data obtained have shown that there is possible influence on central nervous system functioning. The article ends with prospects of further

  19. Functional divisions for visual processing in the central brain of flying Drosophila

    Science.gov (United States)

    Weir, Peter T.; Dickinson, Michael H.

    2015-01-01

    Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit. PMID:26324910

  20. Effects of high fructose diets on central appetite signaling and cognitive function

    Directory of Open Access Journals (Sweden)

    Katrien eLowette

    2015-03-01

    Full Text Available The consumption of fructose has increased tremendously over the last five decades, which is to a large extent due to the development of high fructose corn syrup (HFCS, a commercial sugar additive that contains high amounts of free fructose. HFCS is often added to processed food and beverages partly because it is a powerful sweetener but even more so because the production is cheap. Although fructose in combination with fiber, vitamins and minerals, as present in fruits, is a healthy source of energy, isolated fructose, in processed food products has been associated with several health disorders such as insulin resistance and hypertension. Apart from its metabolic consequences, a growing body of literature suggests that free fructose can also affect neuronal systems. High fructose intake may on the one hand affect central appetite regulation by altering specific components of the endocannabinoid system. On the other hand it appears to impact on cognitive function by affecting phosphorylation levels of insulin receptor, synapsin 1 and synaptophysin. The present report reviews the recent evidence showing a negative effect of free fructose consumption on central appetite control, as well as cognitive function.

  1. Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review

    Science.gov (United States)

    Wang, Huiying; Lee, In-Seon; Braun, Christoph; Enck, Paul

    2016-01-01

    To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used Bifidobacterium (eg, B. longum, B. breve, and B. infantis) and Lactobacillus (eg, L. helveticus, and L. rhamnosus), with doses between 109 and 1010 colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future. PMID:27413138

  2. Using optical coherence tomography (OCT) imaging in the evaluation of airway dynamics (Conference Presentation)

    Science.gov (United States)

    Szabari, Margit V.; Kelly, Vanessa J.; Applegate, Matthew B.; Chee, Chunmin; Tan, Khay M.; Hariri, Lida P.; Harris, R. Scott; Winkler, Tilo; Suter, Melissa J.

    2016-03-01

    Asthma is a chronic disease resulting in periodic attacks of coughing and wheezing due to temporarily constricted and clogged airways. The pathophysiology of asthma and the process of airway narrowing are not completely understood. Appropriate in vivo imaging modality with sufficient spatial and temporal resolution to dynamically assess the behavior of airways is missing. Optical coherence tomography (OCT) enables real-time evaluation of the airways during dynamic and static breathing maneuvers. Our aim was to visualize the structure and function of airways in healthy and Methacholine (MCh) challenged lung. Sheep (n=3) were anesthetized, mechanically ventilated and imaged with OCT in 4 dependent and 4 independent airways both pre- and post-MCh administration. The OCT system employed a 2.4 Fr (0.8 mm diameter) catheter and acquired circumferential cross-sectional images in excess of 100 frames per second during dynamic tidal breathing, 20 second static breath-holds at end-inspiration and expiration pressure, and in a response to a single deep inhalation. Markedly different airway behavior was found in dependent versus non-dependent airway segments before and after MCh injection. OCT is a non-ionizing light-based imaging modality, which may provide valuable insight into the complex dynamic behavior of airway structure and function in the normal and asthmatic lung.

  3. 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...

  4. Validation of airway resistance models for predicting pressure loss through anatomically realistic conducting airway replicas of adults and children.

    Science.gov (United States)

    Borojeni, Azadeh A T; Noga, Michelle L; Martin, Andrew R; Finlay, Warren H

    2015-07-16

    This work describes in vitro measurement of the total pressure loss at varying flow rate through anatomically realistic conducting airway replicas of 10 children, 4 to 8 years old, and 5 adults. Experimental results were compared with analytical predictions made using published airway resistance models. For the adult replicas, the model proposed by van Ertbruggen et al. (2005. J. Appl. Physiol. 98, 970-980) most accurately predicted central conducting airway resistance for inspiratory flow rates ranging from 15 to 90 L/min. Models proposed by Pedley et al. (1970. J. Respir. Physiol. 9, 371-386) and by Katz et al. (2011. J. Biomech. 44, 1137-1143) also provided reasonable estimates, but with a tendency to over predict measured pressure loss for both models. For child replicas, the Pedley and Katz models both provided good estimation of measured pressure loss at flow rates representative of resting tidal breathing, but under predicted measured values at high inspiratory flow rate (60 L/min). The van Ertbruggen model, developed based on flow simulations performed in an adult airway model, tended to under predict measured pressure loss through the child replicas across the range of flow rates studied (2 to 60 L/min). These results are intended to provide guidance for selection of analytical pressure loss models for use in predicting airway resistance and ventilation distribution in adults and children.

  5. Determination of sex by discriminant function analysis of mandibles from a Central Indian population

    Directory of Open Access Journals (Sweden)

    Kanchankumar P Wankhede

    2015-01-01

    Full Text Available Context: Identification of sex from skeletal remains is one of the important forensic considerations. Discriminant function analysis is increasingly used to determine the sex from skeleton. Aims: To develop discriminant function to determine sex from mandible in a Central Indian population. Settings and Design: This was a prospective study done at the Department of Anatomy. Materials and Methods: The mandibles used in the present study were from the museum specimens. Only 82 adult mandibles (55 male and 27 female that had been preserved were selected. Ten mandibular parameters were measured. Statistical Analysis Used: Statistical analysis was conducted using Statistical Package for Social Sciences (SPSS for Windows, version 16. The level of statistical significance was set at P < 0.05. Results: Using stepwise discriminant function analysis, only six variables were selected as the best discriminant between sexes, with the projection length of corpus mandibulae being the most dimorphic. It was observed that sex classification accuracy of the discriminant functions ranged from 57.3 to 80.5% for the individual variables, 81.7% for the stepwise method, and 85.4% for the direct method. Conclusion: The results of the study show that mandibles can be used for determining sex and the results are comparable with other similar studies. The studied mandibular variables showed sexual dimorphism with an accuracy comparable with other skeletal remains, next to cranium and pelvis.

  6. [Effects of electromagnetic field from cellular phones on selected central nervous system functions: a literature review].

    Science.gov (United States)

    Bak, Marek; Zmyślony, Marek

    2010-01-01

    In the opinion of some experts, a growing emission of man-made electromagnetic fields (EMF), also known as electromagnetic is a source of continuously increasing health hazards to the general population. Due to their large number and very close proximity to the user's head, mobile phones deserve special attention. This work is intended to give a systematic review of objective studies, assessing the effects of mobile phone EMF on the functions of the central nervous system (CNS) structures. Our review shows that short exposures to mobile phone EMF, experienced by telephone users during receiving calls, do not affect the cochlear function. Effects of GSM mobile phone EMF on the conduction of neural impulses from the inner car neurons to the brainstem auditory centres have not been detected either. If Picton's principle, saying that P300 amplitude varies with the improbability of the targets and its latency varies with difficulty of discriminating the target stimulus from standard stimuli, is true, EMF changes the improbability of the targets without hindering their discrimination. Experiments with use of indirect methods do not enable unequivocal verification of EMF effects on the cognitive functions due to the CNS anatomical and functional complexity. Thus, it seems advisable to develop a model of EMF effects on the excitable brain structures at the cellular level.

  7. Diverse functional roles of lipocalin-2 in the central nervous system.

    Science.gov (United States)

    Jha, Mithilesh Kumar; Lee, Shinrye; Park, Dong Ho; Kook, Hyun; Park, Keun-Gyu; Lee, In-Kyu; Suk, Kyoungho

    2015-02-01

    Lipocalin-2 (LCN2) is an acute phase protein with multiple functions that has garnered a great deal of interest over the last decade. However, its precise role in the pathophysiology of the central nervous system (CNS) remains to be outlined. Emerging evidence indicates that LCN2 is synthesized and secreted as an inducible factor from activated microglia, reactive astrocytes, neurons, and endothelial cells in response to inflammatory, infectious, or injurious insults. More recently, it has been recognized as a modulatory factor for diverse cellular phenotypes in the CNS, such as cell death, survival, morphology, migration, invasion, differentiation, and functional polarization. LCN2 induces chemokine production in the CNS in response to inflammatory challenges, and actively participates in the innate immune response, cellular influx of iron, and regulation of neuroinflammation and neurodegeneration. LCN2 also modulates several biobehavioral responses including pain hypersensitivity, cognitive functions, emotional behaviors, depression, neuronal excitability, and anxiety. This review covers recent advances in our knowledge regarding functional roles of LCN2 in the CNS, and discusses how LCN2 acts as an autocrine mediator of astrocytosis, a chemokine inducer, and a modulator of various cellular phenotypes in the CNS. We finally explore the possibilities and challenges of employing LCN2 as a signature of several CNS anomalies.

  8. Optimal surface segmentation using flow lines to quantify airway abnormalities in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Petersen, Jens; Nielsen, Mads; Lo, Pechin Chien Pau

    2014-01-01

    .5%, the alternative approach in 11.2%, and in 20.3% no method was favoured. Airway abnormality measurements obtained with the method on 490 scan pairs from a lung cancer screening trial correlate significantly with lung function and are reproducible; repeat scan R(2) of measures of the airway lumen diameter and wall...

  9. FVC to slow inspiratory vital capacity ratio - A potential marker for small airways obstruction

    NARCIS (Netherlands)

    Cohen, Judith; Postma, Dirkje S.; Vink-Klooster, Karin; van der Bij, Wim; Verschuuren, Erik; ten Hacken, Nick H. T.; Koeter, Gerard H.; Douma, W. Rob

    2007-01-01

    Background: The ratio of FVC to slow inspiratory vital capacity (SVC) has been reported to reflect small airways obstruction, but its validity as such is still unclear. The aim of this study was to assess the applicability of the FVC/SVC ratio as a marker of small airways function in patients with b

  10. 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 differentiate between airway and non-airway voxels. This is in contrast to previous works that use either intensity alone or hand crafted models of airway appearance. We show that the appearance model can be trained with a set of easily acquired, incomplete, airway tree segmentations. A vessel orientation...... similarity measure is introduced, which indicates how similar the orientation of an airway candidate is to the orientation of the neighboring vessel. We use this vessel orientation similarity measure to overcome regions in the airway tree that have a low response from the appearance model. The proposed...

  11. Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices.

    Directory of Open Access Journals (Sweden)

    Tjitske A Oenema

    Full Text Available Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A or TGF-β receptor kinase (SB431542 prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.

  12. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma.

    Science.gov (United States)

    Caceres, Ana I; Brackmann, Marian; Elia, Maxwell D; Bessac, Bret F; del Camino, Donato; D'Amours, Marc; Witek, JoAnn S; Fanger, Chistopher M; Chong, Jayhong A; Hayward, Neil J; Homer, Robert J; Cohn, Lauren; Huang, Xiaozhu; Moran, Magdalene M; Jordt, Sven-Eric

    2009-06-02

    Asthma is an inflammatory disorder caused by airway exposures to allergens and chemical irritants. Studies focusing on immune, smooth muscle, and airway epithelial function revealed many aspects of the disease mechanism of asthma. However, the limited efficacies of immune-directed therapies suggest the involvement of additional mechanisms in asthmatic airway inflammation. TRPA1 is an irritant-sensing ion channel expressed in airway chemosensory nerves. TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma. Here, we examined the role of TRPA1 in allergic asthma in the murine ovalbumin model. Strikingly, genetic ablation of TRPA1 inhibited allergen-induced leukocyte infiltration in the airways, reduced cytokine and mucus production, and almost completely abolished airway hyperreactivity to contractile stimuli. This phenotype is recapitulated by treatment of wild-type mice with HC-030031, a TRPA1 antagonist. HC-030031, when administered during airway allergen challenge, inhibited eosinophil infiltration and prevented the development of airway hyperreactivity. Trpa1(-/-) mice displayed deficiencies in chemically and allergen-induced neuropeptide release in the airways, providing a potential explanation for the impaired inflammatory response. Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge. TRPA1 may represent a promising pharmacological target for the treatment of asthma and other allergic inflammatory conditions.

  13. Upper airway resistance syndrome.

    Science.gov (United States)

    Montserrat, J M; Badia, J R

    1999-03-01

    This article reviews the clinical picture, diagnosis and management of the upper airway resistance syndrome (UARS). Presently, there is not enough data on key points like the frequency of UARS and the morbidity associated with this condition. Furthermore, the existence of LIARS as an independent sleep disorder and its relation with snoring and obstructive events is in debate. The diagnosis of UARS is still a controversial issue. The technical limitations of the classic approach to monitor airflow with thermistors and inductance plethysmography, as well as the lack of a precise definition of hypopnea, may have led to a misinterpretation of UARS as an independent diagnosis from the sleep apnea/hypopnea syndrome. The diagnosis of this syndrome can be missed using a conventional polysomnographic setting unless appropriate techniques are applied. The use of an esophageal balloon to monitor inspiratory effort is currently the gold standard. However, other sensitive methods such as the use of a pneumotachograph and, more recently, nasal cannula/pressure transducer systems or on-line monitoring of respiratory impedance with the forced oscillation technique may provide other interesting possibilities. Recognition and characterization of this subgroup of patients within sleep breathing disorders is important because they are symptomatic and may benefit from treatment. Management options to treat UARS comprise all those currently available for sleep apnea/hypopnea syndrome (SAHS). However, the subset of patients classically identified as LIARS that exhibit skeletal craneo-facial abnormalities might possibly obtain further benefit from maxillofacial surgery.

  14. Linking carbon storage with functional diversity in tropical rainforest in the central Congo Basin

    Science.gov (United States)

    Verbeeck, Hans; Kearsley, Elizabeth; Bauters, Marijn; Beeckman, Hans; Huygens, Dries; Steppe, Kathy; Boeckx, Pascal

    2015-04-01

    This presentation will show an overview of results of the COBIMFO project (Congo basin integrated monitoring for forest carbon mitigation and biodiversity). In the framework of this project we have established 21 permanent 1 ha sampling plots in different forest types in the Yangambi reserve. This UNESCO Man and Biosphere reserve has an area of more than 6000 km² and is located in the heart of the Congo Basin near the Yangambi research station (DR Congo). Analysis of the inventory data of these plots revealed that carbon stocks in mature forests in this area of the Congo Basin are significantly lower (24%) than stocks recorded in the outer regions of the basin. These lower stocks are attributed to a lower maximal tree height (Kearsley et al. 2013). In addition to the carbon inventories we collected leaf and wood samples on all species within 95% basal area of each of the Yangambi plots. A total of 995 individuals were sampled, covering 123 tree species. On the samples we measured 15 traits related to leaf and wood morphology and functioning. In the presented study, relationships between the observed functional diversity and biomass are analysed. One of the remarkable results of our analysis is that species with a high functional distinctiveness have a low contribution to the basal area and the carbon stocks. In contrast, species with a high contribution to the carbon stock have a low contribution to the functional diversity. Similar patterns have been observed elsewhere (e.g. Amazon basin), but are now for the first time confirmed for central African rainforest. Finally, we also present the first results of an analysis of carbons stocks and functional diversity in tropical plantations from a unique 70-years old tree diversity experiment that was established during the colonial period at the Yangambi research station. Kearsley, E., de Haulleville, T., Hufkens, K., Kidimbu, A., Toirambe, B., Baert, G., Huygens, D., Kebede, Y., Defourny, P., Bogaert, J., Beeckman, H

  15. Constraining the Lithospheric Structure of the Central Andes Using P- and S- wave Receiver Functions

    Science.gov (United States)

    Ryan, J. C.; Beck, S. L.; Zandt, G.; Wagner, L. S.; Minaya, E.; Tavera, H.

    2014-12-01

    The Central Andean Plateau (CAP) has elevations in excess of 3 km, and is part of the Andean Cordillera that resulted in part from shortening along the western edge of South America as it was compressed between the subducting Nazca plate and underthrusting Brazilian cratonic lithosphere. We calculated P- and S-wave receiver functions for the Central Andean Uplift and Geodynamics of High Topography (CAUGHT) temporary deployment of broadband seismometers in the Bolivian orocline (12°-20°S) region to investigate crustal thickness and lithospheric structure. Migration of the receiver functions is done using common conversion point (CCP) stacks through a 3D shear velocity model from ambient noise tomography (Ward et al., 2013). The P- and S-wave receiver functions provide similar estimates of the depth to Moho under the CAP. Crustal thicknesses include 60-65 km thick crust underneath the Bolivian Altiplano, crust that varies from ~70 km to ~50 km underneath the Eastern Cordillera and Interandean zone, and thins to 50 to 40 km crust in the Subandes and the edge of the foreland. The variable crustal thickness of the Eastern Cordillera and Interandean zone ranges from >70 km associated with the Los Frailes volcanic field at 19°-20°S to ~55 km beneath the 6 km peaks of the Cordillera Real at ~16°S. From our S-wave receiver functions, that have no multiples that can interfere with deeper structure, we also identify structures below the Moho. Along a SW-NE line that runs near La Paz where we have our highest station density, the S-wave CCP receiver-function stacks show a strong negative polarity arrival at a depth of ~120 km from the eastern edge of the Altiplano to the Subandean zone. We suggest this may be a good candidate for the base of the CAP lithosphere. In addition, above this depth the mantle is strongly layered, suggesting that there is not a simple high velocity mantle lithosphere associated with the continental lithosphere underthrusting the Andean orogen

  16. Neuromotor recovery from stroke: Computational models at central, functional, and muscle synergy level

    Directory of Open Access Journals (Sweden)

    Maura eCasadio

    2013-08-01

    Full Text Available Computational models of neuromotor recovery after a stroke might help to unveil the underlying physiological mechanisms and might suggest how to make recovery faster and more effective. At least in principle, these models could serve: (i To provide testable hypotheses on the nature of recovery; (ii To predict the recovery of individual patients; (iii To design patient-specific ’optimal’ therapy, by setting the treatment variables for maximizing the amount of recovery or for achieving a better generalization of the learned abilities across different tasks.Here we review the state of the art of computational models for neuromotor recovery through exercise, and their implications for treatment. We show that to properly account for the computational mechanisms of neuromotor recovery, multiple levels of description need to be taken into account. The review specifically covers models of recovery at central, functional and muscle synergy level.

  17. Central and peripheral nervous system functions are independently disturbed in HIV-1 infected patients.

    Science.gov (United States)

    von Giesen, Hans-Jürgen; Köller, Hubertus; Hefter, Harald; Arendt, Gabriele

    2002-06-01

    We examined the peripheral nervous system (PNS) (nerve conduction velocity (NCV)) and the central nervous system (CNS) (basal ganglia-mediated psychomotor speed) in 93 males seropositive for human immunodeficiency virus type 1 (HIV-1) with no prior history of opportunistic brain disease, antiretroviral treatment or intravenous drug use. Patients with different degrees of slowing of peroneal and sural NCV showed no significant differences in psychomotor speed as assessed by tremor peak frequency, most rapid alternating movements, reaction times and contraction times. There was no significant correlation between psychomotor measures and NCV. Psychomotor slowing test findings were independent from peripheral nervous system damage indicating uncorrelated disturbances of CNS and PNS function in HIV-1 infection. Differences in HIV-1 viral quasispecies or host responses may determine the predominance of CNS or PNS injury.

  18. A Simple Adaptive Transfer Function for Deriving the Central Blood Pressure Waveform from a Radial Blood Pressure Waveform.

    Science.gov (United States)

    Gao, Mingwu; Rose, William C; Fetics, Barry; Kass, David A; Chen, Chen-Huan; Mukkamala, Ramakrishna

    2016-09-14

    Generalized transfer functions (GTFs) are available to compute the more relevant central blood pressure (BP) waveform from a more easily measured radial BP waveform. However, GTFs are population averages and therefore may not adapt to variations in pulse pressure (PP) amplification (ratio of radial to central PP). A simple adaptive transfer function (ATF) was developed. First, the transfer function is defined in terms of the wave travel time and reflection coefficient parameters of an arterial model. Then, the parameters are estimated from the radial BP waveform by exploiting the observation that central BP waveforms exhibit exponential diastolic decays. The ATF was assessed using the original data that helped popularize the GTF. These data included radial BP waveforms and invasive reference central BP waveforms from cardiac catheterization patients. The data were divided into low, middle, and high PP amplification groups. The ATF estimated central BP with greater accuracy than GTFs in the low PP amplification group (e.g., central systolic BP and PP root-mean-square-errors of 3.3 and 4.2 mm Hg versus 6.2 and 7.1 mm Hg; p ≤ 0.05) while showing similar accuracy in the higher PP amplification groups. The ATF may permit more accurate, non-invasive central BP monitoring in elderly and hypertensive patients.

  19. Impaired Neural Structure and Function Contributing to Autonomic Symptoms in Congenital Central Hypoventilation Syndrome

    Directory of Open Access Journals (Sweden)

    Ronald M Harper

    2015-10-01

    Full Text Available Congenital central hypoventilation syndrome (CCHS patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover

  20. Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

    Directory of Open Access Journals (Sweden)

    Elaine G Boland

    Full Text Available Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN with those from healthy volunteers (HV. Twenty-four participants (n = 12 MM-CIPN, n = 12 HV underwent Blood Oxygen Level-Dependent (BOLD fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected. Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected. Significant positive correlation existed between the total neuropathy score (reduced version and activation in the frontal operculum (close to insular cortex during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87. Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

  1. Caffeine and central noradrenaline: effects on mood, cognitive performance, eye movements and cardiovascular function.

    Science.gov (United States)

    Smith, Andrew; Brice, Carolyn; Nash, Jon; Rich, Neil; Nutt, David J

    2003-09-01

    There have been numerous studies on the effects of caffeine on behaviour and cardiovascular function. It is now important to clarify the mechanisms that underlie such effects, and the main objective of the present study was to investigate whether changes in central noradrenaline underlie some of the behavioural and cardiovascular effects of caffeine. This was examined using a clonidine challenge paradigm. Twenty-four healthy volunteers were assigned to one of four conditions: (i) clonidine/caffeine; (ii) clonidine/placebo; (iii) placebo/caffeine: (iv) placebo/placebo. Baseline measurements of mood, cognitive performance, saccadic eye movements and cardiovascular function were recorded. Subsequently, volunteers were given either clonidine (200 microg) or placebo and consumed coffee containing caffeine (1.5 mg/kg) or placebo. The test battery was then repeated 30 min, 150 min and 270 min later. A second cup of coffee (with the same amount of caffeine as the first) was consumed 120 min after the first cup. The results showed that clonidine reduced alertness, impaired many aspects of performance and slowed saccadic eye movements; caffeine removed many of these impairments. Both clonidine and caffeine influenced blood pressure (clonidine reduced it, caffeine raised it) but the effects appeared to be independent, suggesting that separate mechanisms were involved. In addition, there were some behavioural effects of caffeine that were independent of the clonidine effect (e.g. effects on speed of encoding of new information) and these may reflect other neurotransmitter systems (e.g cholinergic effects). Overall, the results suggest that caffeine counteracts reductions in the turnover of central noradrenaline. This mechanism may underlie the beneficial effects of caffeine seen in low alertness states.

  2. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Puchelle, Edith; Zahm, Jean-Marie; Tournier, Jean-Marie; Coraux, Christelle

    2006-11-01

    In chronic obstructive pulmonary disease (COPD), exacerbations are generally associated with several causes, including pollutants, viruses, bacteria that are responsible for an excess of inflammatory mediators, and proinflammatory cytokines released by activated epithelial and inflammatory cells. The normal response of the airway surface epithelium to injury includes a succession of cellular events, varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even complete denudation of the basement membrane. The epithelium then has to repair and regenerate to restore its functions, through several mechanisms, including basal cell spreading and migration, followed by proliferation and differentiation of epithelial cells. In COPD, the remodeling of the airway epithelium, such as squamous metaplasia and mucous hyperplasia that occur during injury, may considerably disturb the innate immune functions of the airway epithelium. In vitro and in vivo models of airway epithelial wound repair and regeneration allow the study of the spatiotemporal modulation of cellular and molecular interaction factors-namely, the proinflammatory cytokines, the matrix metalloproteinases and their inhibitors, and the intercellular adhesion molecules. These factors may be markedly altered during exacerbation periods of COPD and their dysregulation may induce remodeling of the airway mucosa and a leakiness of the airway surface epithelium. More knowledge of the mechanisms involved in airway epithelium regeneration may pave the way to cytoprotective and regenerative therapeutics, allowing the reconstitution of a functional, well-differentiated airway epithelium in COPD.

  3. Aging increases upper airway collapsibility in Fischer 344 rats.

    Science.gov (United States)

    Ray, Andrew D; Ogasa, Toshiyuki; Magalang, Ulysses J; Krasney, John A; Farkas, Gaspar A

    2008-11-01

    The upper airway muscles play an important role in maintaining upper airway collapsibility, and the incidence of sleep-disordered breathing increases with age. We hypothesize that the increase in airway collapsibility with increasing age can be linked to changes in upper airway muscle mechanics and structure. Eight young (Y: 6 mo) and eight old (O: 30 mo) Fischer 344 rats were anesthetized and mechanically ventilated, and the pharyngeal pressure associated with flow limitation (Pcrit) was measured 1) with the hypoglossal (cnXII) nerve intact, 2) following bilateral cnXII denervation, and 3) during cnXII stimulation. With the cnXII intact, the upper airways of older rats were more collapsible compared with their younger counterparts [Pcrit = -7.1 +/- 0.6 (SE) vs. -9.5 +/- 0.7 cmH2O, respectively; P = 0.033]. CnXII denervation resulted in an increase in Pcrit such that Pcrit became similar in both groups (O: -4.2 +/- 0.5 cmH2O; Y: -5.4 +/- 0.5 cmH2O). In all rats, cnXII stimulation decreased Pcrit (less collapsible) in both groups (O: -11.3 +/- 1.0 cmH2O; Y: -10.2 +/- 1.0 cmH2O). The myosin heavy chain composition of the genioglossus muscle demonstrated a decrease in the percentage of the IIb isoform (38.3 +/- 2.5 vs. 21.7 +/- 1.7%; P collapsible with age and that the increase in upper airway collapsibility with age is likely related to altered neural control rather than to primary alterations in upper airway muscle structure and function.

  4. Neuropeptides control the dynamic behavior of airway mucosal dendritic cells.

    Science.gov (United States)

    Voedisch, Sabrina; Rochlitzer, Sabine; Veres, Tibor Z; Spies, Emma; Braun, Armin

    2012-01-01

    The airway mucosal epithelium is permanently exposed to airborne particles. A network of immune cells patrols at this interface to the environment. The interplay of immune cells is orchestrated by different mediators. In the current study we investigated the impact of neuronal signals on key functions of dendritic cells (DC). Using two-photon microscopic time-lapse analysis of living lung sections from CD11c-EYFP transgenic mice we studied the influence of neuropeptides on airway DC motility. Additionally, using a confocal microscopic approach, the phagocytotic capacity of CD11c(+) cells after neuropeptide stimulation was determined. Electrical field stimulation (EFS) leads to an unspecific release of neuropeptides from nerves. After EFS and treatment with the neuropeptides vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP), airway DC in living lung slices showed an altered motility. Furthermore, the EFS-mediated effect could partially be blocked by pre-treatment with the receptor antagonist CGRP(8-37). Additionally, the phagocytotic capacity of bone marrow-derived and whole lung CD11c(+) cells could be inhibited by neuropeptides CGRP, VIP, and Substance P. We then cross-linked these data with the in vivo situation by analyzing DC motility in two different OVA asthma models. Both in the acute and prolonged OVA asthma model altered neuropeptide amounts and DC motility in the airways could be measured. In summary, our data suggest that neuropeptides modulate key features motility and phagocytosis of mouse airway DC. Therefore altered neuropeptide levels in airways during allergic inflammation have impact on regulation of airway immune mechanisms and therefore might contribute to the pathophysiology of asthma.

  5. Quantitative analysis of airway abnormalities in CT

    DEFF Research Database (Denmark)

    Petersen, Jens; Lo, P.; Nielsen, Mads;

    2010-01-01

    A coupled surface graph cut algorithm for airway wall segmentation from Computed Tomography (CT) images is presented. Using cost functions that highlight both inner and outer wall borders, the method combines the search for both borders into one graph cut. The proposed method is evaluated on 173...... Area (IA) and Wall Area percentage (WA%) was measured by the proposed method on a total of 723 CT scans from a lung cancer screening study. These measures were significantly different for participants with Chronic Obstructive Pulmonary Disease (COPD) compared to asymptomatic participants. Furthermore...

  6. Allergen uptake, activation, and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice.

    Directory of Open Access Journals (Sweden)

    Ian P Lewkowich

    Full Text Available Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs are important mediators of allergic asthma, yet the precise signals which render endogenous DCs "pro-asthmatic", and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J, or resistant (C3H to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23, whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness.

  7. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

    Science.gov (United States)

    Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

    2015-11-15

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy.

  8. Treating asthma means treating airway smooth muscle cells

    NARCIS (Netherlands)

    Zuyderduyn, S; Sukkar, M B; Fust, A; Dhaliwal, S; Burgess, J K

    2008-01-01

    Asthma is characterised by airway hyperresponsiveness, airway inflammation and airway remodelling. Airway smooth muscle cells are known to be the main effector cells of airway narrowing. In the present paper, studies will be discussed that have led to a novel view of the role of airway smooth muscle

  9. Signaling and regulation of G protein-coupled receptors in airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Penn Raymond B

    2003-03-01

    Full Text Available Abstract Signaling through G protein-coupled receptors (GPCRs mediates numerous airway smooth muscle (ASM functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that have been identified in ASM cells, and discuss the extent to which signaling via these GPCRs has been characterized and linked to distinct ASM functions. In addition, we examine the role of GPCR signaling and its regulation in asthma and asthma treatment, and suggest an integrative model whereby an imbalance of GPCR-derived signals in ASM cells contributes to the asthmatic state.

  10. Application of disposable laryngeal mask airway in functional endoscopic sinus surgery%喉罩通气在鼻内窥镜手术麻醉中的应用

    Institute of Scientific and Technical Information of China (English)

    姚东旭; 陈继彬

    2012-01-01

    Objective To assess the clinical performance of disposable laryngeal mask airway (LMA) by comparing the effect on hemodynamics and respiratory mechanics of LMA with endotracheal intubation (ETT) in functional endoscopic sinus surgery. Methods 40 patients undergoing functional endoscopic sinus surgeries were enrolled in the study. They were evenly and randomly assigned into LMA group and ETT group who were either applied with LMA or ETT after induction of general anesthesia. Mean arterial pressure (MAP), heart rate (HR) and oxygen saturation (SpO2) were recorded before and after the induction of anesthesia, as well as right after the inserting and removal of ETT or LMA. Parameters for respiratory mechanics including peak inspiratory pressure (PIP), plateau airway pressure (Pplateau), mean airway pressure (Pmean), positive end expiratory pressure (PEEP), peak inspiratory flow (FImax), peak expiratory flow (FEmax) were also recorded at 5, 15 and 30 minutes after induction. Meanwhile, the first-time insertion success rate and complications up to 24 hours after extubation for LMA and ETT were compared as well. Results The MAP and HR at each recorded points in LMA group were significantly lower than those in ETT group (P<0. 05) , and the PIP, Pplateau, Pmean and FEmax at each recorded points in LAM group were also significantly lower compared with those in ETT group (P<0. 05) .Complications such as coughing, pharyngeal pain and muscular soreness were much less noted in LMA group than in TT group (P<0. 05) . Conclusions The disposable laryngeal mask airway is much safer than endotracheal intubation and may be an effective device for positive pressure ventilation in patients requiring functional endoscopic sinus surgery.%目的 比较一次性喉罩与气管插管用于鼻内窥镜手术麻醉中对血流动力学及呼吸动力学的影响.方法 将拟在全身麻醉下择期行鼻内窥镜手术的40例患者随机分为喉罩组(LMA)和气管插管组(TT),每组各20

  11. Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

    OpenAIRE

    Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, Maria A.; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Jordan K. Zjawiony; Izzo, Angelo A; Capasso, Raffaele; Roviezzo, Fiorentina

    2017-01-01

    Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice we...

  12. Multiscale Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

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

    2009-01-01

    that is trained to differentiate between airway and non-airway voxels. Vessel and airway orientation information are used in the form of a vessel orientation similarity measure, which indicates how similar the orientation of the an airway candidate is to the orientation of the neighboring vessel. The method...... is evaluated within EXACT’09 on a diverse set of CT scans. Results show a favorable combination of a relatively large portion of the tree detected correctly with very few false positives....

  13. Barrier function in the peripheral and central nervous system-a review.

    Science.gov (United States)

    Reinhold, A K; Rittner, H L

    2017-01-01

    The peripheral (PNS) and central nervous system (CNS) are delicate structures, highly sensitive to homeostatic changes-and crucial for basic vital functions. Thus, a selection of barriers ensures the protection of the nervous system from noxious blood-borne or surrounding stimuli. In this chapter, anatomy and functioning of the blood-nerve (BNB), the blood-brain (BBB), and the blood-spinal cord barriers (BSCB) are presented and the key tight junction (TJ) proteins described: claudin-1, claudin-3, claudin-5, claudin-11, claudin-12, claudin-19, occludin, Zona occludens-1 (ZO-1), and tricellulin are by now identified as relevant for nerval barriers. Different diseases can lead to or be accompanied by neural barrier disruption, and impairment of these barriers worsens pathology. Peripheral nerve injury and inflammatory polyneuropathy cause an increased permeability of BNB as well as BSCB, while, e.g., diseases of the CNS such as amyotrophic lateral sclerosis, multiple sclerosis, spinal cord injury, or Alzheimer's disease can progress and worsen through barrier dysfunction. Moreover, the complex role and regulation of the BBB after ischemic stroke is described. On the other side, PNS and CNS barriers hamper the delivery of drugs in diseases when the barrier is intact, e.g., in certain neurodegenerative diseases or inflammatory pain. Understanding of the barrier - regulating processes has already lead to the discovery of new molecules as drug enhancers. In summary, the knowledge of all of these mechanisms might ultimately lead to the invention of drugs to control barrier function to help ameliorating or curing neurological diseases.

  14. Empirical transfer functions for stations in the Central California seismological network

    Science.gov (United States)

    Bakun, W.H.; Dratler, Jay

    1976-01-01

    A sequence of calibration signals composed of a station identification code, a transient from the release of the seismometer mass at rest from a known displacement from the equilibrium position, and a transient from a known step in voltage to the amplifier input are generated by the automatic daily calibration system (ADCS) now operational in the U.S. Geological Survey central California seismographic network. Documentation of a sequence of interactive programs to compute, from the calibration data, the complex transfer functions for the seismographic system (ground motion through digitizer) the electronics (amplifier through digitizer), and the seismometer alone are presented. The analysis utilizes the Fourier transform technique originally suggested by Espinosa et al (1962). Section I is a general description of seismographic calibration. Section II contrasts the 'Fourier transform' and the 'least-squares' techniques for analyzing transient calibration signals. Theoretical consideration for the Fourier transform technique used here are described in Section III. Section IV is a detailed description of the sequence of calibration signals generated by the ADCS. Section V is a brief 'cookbook description' of the calibration programs; Section VI contains a detailed sample program execution. Section VII suggests the uses of the resultant empirical transfer functions. Supplemental interactive programs by which smooth response functions, suitable for reducing seismic data to ground motion, are also documented in Section VII. Appendices A and B contain complete listings of the Fortran source Codes while Appendix C is an update containing preliminary results obtained from an analysis of some of the calibration signals from stations in the seismographic network near Oroville, California.

  15. Airway microbiota and acute respiratory infection in children.

    Science.gov (United States)

    Hasegawa, Kohei; Camargo, Carlos A

    2015-01-01

    Acute respiratory infections (ARIs), such as bronchiolitis and pneumonia, are the leading cause of hospitalization of infants in the US. While the incidence and severity of ARI can vary widely among children, the reasons for these differences are not fully explained by traditional risk factors (e.g., prematurity, viral pathogens). The recent advent of molecular diagnostic techniques has revealed the presence of highly functional communities of microbes inhabiting the human body (i.e., microbiota) that appear to influence development of local and systemic immune response. We propose a 'risk and resilience' model in which airway microbiota are associated with an increased (risk microbiota) or decreased (resilience microbiota) incidence and severity of ARI in children. We also propose that modulating airway microbiota (e.g., from risk to resilience microbiota) during early childhood will optimize airway immunity and, thereby, decrease ARI incidence and severity in children.

  16. Pharmacogenetics, pharmacogenomics and airway disease

    Directory of Open Access Journals (Sweden)

    Hall Ian P

    2001-11-01

    Full Text Available Abstract The availability of a draft sequence for the human genome will revolutionise research into airway disease. This review deals with two of the most important areas impinging on the treatment of patients: pharmacogenetics and pharmacogenomics. Considerable inter-individual variation exists at the DNA level in targets for medication, and variability in response to treatment may, in part, be determined by this genetic variation. Increased knowledge about the human genome might also permit the identification of novel therapeutic targets by expression profiling at the RNA (genomics or protein (proteomics level. This review describes recent advances in pharmacogenetics and pharmacogenomics with regard to airway disease.

  17. Phenotype modulation of airway smooth muscle in asthma

    NARCIS (Netherlands)

    Wright, David B.; Trian, Thomas; Siddiqui, Sana; Pascoe, Chris D.; Johnson, Jill R.; Dekkers, Bart G. J.; Dakshinamurti, Shyamala; Bagchi, Rushita; Burgess, Janette K.; Kanabar, Varsha; Ojo, Oluwaseun O.

    2013-01-01

    The biological responses of airway smooth muscle (ASM) are diverse, in part due to ASM phenotype plasticity. ASM phenotype plasticity refers to the ability of ASM cells to change the degree of a variety of functions, including contractility, proliferation, migration and secretion of inflammatory med

  18. Sleep and upper airway obstruction in children with achondroplasia

    NARCIS (Netherlands)

    Zucconi, M; Weber, G; Castronovo, [No Value; FeriniStrambi, L; Russo, F; Chiumello, G; Smirne, S

    1996-01-01

    Objective: The features of achondroplasia, the most common form of dwarfism, includes short cranial base and midface hypoplasia; both abnormalities increased the risk of upper airway obstruction during sleep, The aim of our study was to evaluate sleep and respiratory function of children with achond

  19. Mechanisms of Cigarette Smoke Effects on Human Airway Smooth Muscle.

    Directory of Open Access Journals (Sweden)

    Mark E Wylam

    Full Text Available Cigarette smoke contributes to or exacerbates airway diseases such as asthma and COPD, where airway hyperresponsiveness and airway smooth muscle (ASM proliferation are key features. While factors such as inflammation contribute to asthma in part by enhancing agonist-induced intracellular Ca(2+ ([Ca(2+]i responses of ASM, the mechanisms by which cigarette smoke affect ASM are still under investigation. In the present study, we tested the hypothesis that cigarette smoke enhances the expression and function of Ca(2+ regulatory proteins leading to increased store operated Ca(2+ entry (SOCE and cell proliferation. Using isolated human ASM (hASM cells, incubated in the presence and absence cigarette smoke extract (CSE we determined ([Ca(2+]i responses and expression of relevant proteins as well as ASM proliferation, reactive oxidant species (ROS and cytokine generation. CSE enhanced [Ca(2+]i responses to agonist and SOCE: effects mediated by increased expression of TRPC3, CD38, STIM1, and/or Orai1, evident by attenuation of CSE effects when siRNAs against these proteins were used, particularly Orai1. CSE also increased hASM ROS generation and cytokine secretion. In addition, we found in the airways of patients with long-term smoking history, TRPC3 and CD38 expression were significantly increased compared to life-long never-smokers, supporting the role of these proteins in smoking effects. Finally, CSE enhanced hASM proliferation, an effect confirmed by upregulation of PCNA and Cyclin E. These results support a critical role for Ca(2+ regulatory proteins and enhanced SOCE to alter airway structure and function in smoking-related airway disease.

  20. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation.

    Directory of Open Access Journals (Sweden)

    Romina Nassini

    Full Text Available BACKGROUND: The transient receptor potential ankyrin 1 (TRPA1 channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1. METHODOLOGY/PRINCIPAL FINDINGS: By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1, a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists, or the neuropeptide substance P (SP, which is released from sensory nerve terminals by capsaicin, acrolein or CS, produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue in bronchoalveolar lavage (BAL fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves. CONCLUSIONS: Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1 activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Efficient delivery of RNA interference oligonucleotides to polarized airway epithelia in vitro.

    Science.gov (United States)

    Ramachandran, Shyam; Krishnamurthy, Sateesh; Jacobi, Ashley M; Wohlford-Lenane, Christine; Behlke, Mark A; Davidson, Beverly L; McCray, Paul B

    2013-07-01

    Polarized and pseudostratified primary airway epithelia present barriers that significantly reduce their transfection efficiency and the efficacy of RNA interference oligonucleotides. This creates an impediment in studies of the airway epithelium, diminishing the utility of loss-of-function as a research tool. Here we outline methods to introduce RNAi oligonucleotides into primary human and porcine airway epithelia grown at an air-liquid interface and difficult-to-transfect transformed epithelial cell lines grown on plastic. At the time of plating, we reverse transfect small-interfering RNA (siRNA), Dicer-substrate siRNA, or microRNA oligonucleotides into cells by use of lipid or peptide transfection reagents. Using this approach we achieve significant knockdown in vitro of hypoxanthine-guanine phosphoribosyltransferase, IL-8, and CFTR expression at the mRNA and protein levels in 1-3 days. We also attain significant reduction of secreted IL-8 in polarized primary pig airway epithelia 3 days posttransfection and inhibition of CFTR-mediated Cl⁻ conductance in polarized air-liquid interface cultures of human airway epithelia 2 wk posttransfection. These results highlight an efficient means to deliver RNA interference reagents to airway epithelial cells and achieve significant knockdown of target gene expression and function. The ability to reliably conduct loss-of-function assays in polarized primary airway epithelia offers benefits to research in studies of epithelial cell homeostasis, candidate gene function, gene-based therapeutics, microRNA biology, and targeting the replication of respiratory viruses.

  3. [Upper airway's 3D analysis of patients with obstructive sleep apnea using tomographic cone beam].

    Science.gov (United States)

    Bruwier, A; Poirrier, A L; Limme, M; Poirrier, R

    2014-12-01

    The progress of medical imaging over the last decades has led to a better understanding of the upper airway structure in sleep-disordered patients. The Obstructive Sleep Apnea Syndrome (OSA) is attributed to a functional narrowing of the upper airway, particularly of the oropharynx, during sleep. This narrowing is multifactorial. We have shown that in 60% cases, the maxilla (nasal pyramid) seems too narrow. A mandible retroposition may also play a dominant role in 30% of the cases. Both scenarios can be combined. Cone Beam Computed Tomography (CBCT) is a new medical imaging technique that permits to visualize the upper airway with less ionizing radiation than the conventional scanner. To date, only five authors have performed an upper airway's 3D analysis of sleep apnea patients with cone beam. A better understanding of the affected segment of the upper airway should help refine treatment options.

  4. The extract of Cordyceps sinensis inhibited airway inflammation by blocking NF-κB activity.

    Science.gov (United States)

    Chiou, Ya-Ling; Lin, Ching-Yuang

    2012-06-01

    Aiming the extract of Cordyceps sinensis significantly inhibits airway inflammation, airway hyperresponsiveness, and the infiltration of eosinophils in the airway of rats and may be related to the modulation of T helper (Th)1 and Th2 cells functions. The mechanisms of C. sinensis involved in modulation of suppression inflammation are not yet determined. In this study, the mechanism involved in the extract of C. sinensis-C.S.3-modulated suppression of inflammation was investigated in vivo and in vitro systems. The results showed that C.S.3 reduced airway inflammation in ovalbumin-induced allergic mice. Furthermore, we found C.S.3 could decrease extracellular signal-regulated kinase 1/2 signaling pathway to suppress activity of nuclear factor-κB in lung cells and cultured airway smooth muscle cells. Conclusion C.S.3 may provide clinical applications for asthma in the future.

  5. A necessary moment condition for the fractional functional central limit theorem

    DEFF Research Database (Denmark)

    Johansen, Søren; Nielsen, Morten Ørregaard

    We discuss the moment condition for the fractional functional central limit theorem (FCLT) for partial sums of x_{t}=Delta^{-d}u_{t}, where d in (-1/2,1/2) is the fractional integration parameter and u_{t} is weakly dependent. The classical condition is existence of q>max(2,(d+1/2)^{-1}) moments...... of the innovation sequence. When d is close to -1/2 this moment condition is very strong. Our main result is to show that under some relatively weak conditions on u_{t}, the existence of q≥max(2,(d+1/2)^{-1}) is in fact necessary for the FCLT for fractionally integrated processes and that q>max(2,(d+1....../2)^{-1}) moments are necessary and sufficient for more general fractional processes. Davidson and de Jong (2000) presented a fractional FCLT where only q>2 finite moments are assumed, which is remarkable because it is the only FCLT where the moment condition has been weakened relative to the earlier condition...

  6. A Necessary Moment Condition for the Fractional Functional Central Limit Theorem

    DEFF Research Database (Denmark)

    Johansen, Søren; Nielsen, Morten Ørregaard

    We discuss the moment condition for the fractional functional central limit theorem (FCLT) for partial sums of x(t)=¿^(-d)u(t), where d ¿ (-1/2,1/2) is the fractional integration parameter and u(t) is weakly dependent. The classical condition is existence of q>max(2,(d+1/2)-¹) moments...... of the innovation sequence. When d is close to -1/2 this moment condition is very strong. Our main result is to show that under some relatively weak conditions on u(t), the existence of q=max(2,(d+1/2)-¹) is in fact necessary for the FCLT for fractionally integrated processes and that q>max(2,(d+1/2)-¹) moments...... are necessary and sufficient for more general fractional processes. Davidson and de Jong (2000) presented a fractional FCLT where only q>2 finite moments are assumed, which is remarkable because it is the only FCLT where the moment condition has been weakened relative to the earlier condition. As a corollary...

  7. The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system.

    Science.gov (United States)

    Carta, Mario; Murru, Luca; Botta, Paolo; Talani, Giuseppe; Sechi, GianPietro; De Riu, PierLuigi; Sanna, Enrico; Biggio, Giovanni

    2006-09-01

    Thiocolchicoside (TCC) is used clinically for its muscle relaxant, anti-inflammatory, and analgesic properties, and it has been shown to interact with gamma-aminobutyric acid (GABA) type A receptors (GABAARs) and strychnine-sensitive glycine receptors in the rat central nervous system. In contrast to a proposed agonistic action at these two types of inhibitory receptors, pharmacological evidence has shown that, under certain conditions, TCC manifests convulsant activity in animals and humans. We now show that the phasic and tonic GABAAR-mediated currents recorded from Purkinje cells and granule neurons, respectively, in parasagittal cerebellar slices from adult male rats were inhibited by TCC in a concentration-dependent manner. The median inhibitory concentrations of TCC for these effects were approximately 0.15 and approximately 0.9 microM, respectively. TCC did not potentiate GABABR-mediated currents in hippocampal slices, suggesting that its muscle relaxant action is not mediated by GABABRs. Intraperitoneal injection of TCC in rats either alone or in combination with negative modulators of GABAergic transmission revealed convulsant and proconvulsant actions of this drug. Our data, consistent with clinical observations of the epileptogenic effect of this compound, suggest that TCC is a potent competitive antagonist of GABAAR function.

  8. A Complete K-band Luminosity Function of the Central 30 PC

    Science.gov (United States)

    Philipp, S.; Mezger, P. G.; Zylka, R.

    1999-06-01

    We have obtained a K band mosaic image of an area Δα times Δ δ ~650'' times 710'' centered approximately on Sgr A*. With a detection limit of SK' ~100 μ Jy and a completeness limit of ~2000 μ Jy our source counts will only be complete for early O-stars, Supergiants and the most luminous red Giants; less luminous stars will merge into an unresolved background continuum. Special care was taken in our observing procedure to recover all of this continuum emission. 6.1 times 104 individual sources were separated from the background continuum by fitting them with modified Lorentzian distributions. For the low-luminosity sources we construct a model K-band luminosity function (KLF) based on a Salpeter IMF, which is compared with the KLF of Baade's Window after readjustment to match the stellar surface density in the mosaic. We obtain the following results: The emission of both point like sources (interpreted as luminous stars) and an unresolved continuum (interpreted as low-mass main sequence (MS) stars) can be fitted by a KLF ~ SK'α consisting of four power-law approximations with different exponents α: The modeled sectors which relate to MS stars have the functional dependences ~ SK'-0.6 and SK' -0.8; the observed KLF, which relates to Giants and Supergiants becomes gradually steeper. Compared to the KLF of Baades Window (Tiede et al., 1995) the KLF of the mosaic shows a clear overabundance of stars with high K band flux densities which is strongest within the central 24'' (~1 pc).

  9. Detection of a new sub-lithospheric discontinuity in Central Europe with S-receiver functions

    Science.gov (United States)

    Kind, Rainer; Handy, Mark R.; Yuan, Xiaohui; Meier, Thomas; Kämpf, Horst; Soomro, Riaz

    2017-03-01

    We used S-receiver functions (i.e. S-to-P converted signals) to study seismic discontinuities in the upper mantle between the Moho and the 410 km discontinuity beneath central Europe. This was done by using c. 49,000 S-receiver functions from c. 700 permanent and temporary broadband stations made available by the open EIDA Archives. Below Phanerozoic Europe we observed expected discontinuities like the Moho, the lithosphere-asthenosphere boundary (LAB), the Lehmann discontinuity and the 410 km discontinuity with an additional overlying low velocity zone. Below the East European Craton (EEC), we observed the Mid-Lithospheric Discontinuity (MLD) at c. 100 km depth as well as the controversial cratonic LAB at c. 200 km depth. At the boundary of the EEC but still below the Phanerozoic surface, we observed downward velocity reductions below the LAB in the following regions: the North German-Polish Plain at about 200 km depth; the Bohemian Massive, north-west dipping from 200 to 300 km depth; the Pannonian Basin, north-east dipping from 150 to 200 km depth underneath the western Carpathians and the EEC. We named this newly observed structure Sub-Lithospheric Discontinuity (SLD). At the northern edge of the Bohemian Massive, we see a sharp vertical step of about 100 km between the SLD below the Bohemian Massive and the North German-Polish Plain. This step follows the surface trace of the Rheic Suture between the continental Saxo-Thuringian and Rheno-Herzynian zones of the Variscan orogen. A preliminary interpretation of these features is that a prong of the cratonic mantle lithosphere penetrated the Phanerozoic asthenosphere during the continental collision at the western and south-western edges of the EEC.

  10. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala.

    Science.gov (United States)

    Varodayan, Florence P; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G; Schweitzer, Paul; Parsons, Loren H; Roberto, Marisa

    2016-07-01

    The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and Type 1 cannabinoid receptor (CB1 ) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not Type 2 cannabinoid receptor (CB2 ) antagonism. After 2-3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naive CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naive and ethanol-exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling.

  11. The serotonergic central nervous system of the Drosophila larva: anatomy and behavioral function.

    Directory of Open Access Journals (Sweden)

    Annina Huser

    Full Text Available The Drosophila larva has turned into a particularly simple model system for studying the neuronal basis of innate behaviors and higher brain functions. Neuronal networks involved in olfaction, gustation, vision and learning and memory have been described during the last decade, often up to the single-cell level. Thus, most of these sensory networks are substantially defined, from the sensory level up to third-order neurons. This is especially true for the olfactory system of the larva. Given the wealth of genetic tools in Drosophila it is now possible to address the question how modulatory systems interfere with sensory systems and affect learning and memory. Here we focus on the serotonergic system that was shown to be involved in mammalian and insect sensory perception as well as learning and memory. Larval studies suggested that the serotonergic system is involved in the modulation of olfaction, feeding, vision and heart rate regulation. In a dual anatomical and behavioral approach we describe the basic anatomy of the larval serotonergic system, down to the single-cell level. In parallel, by expressing apoptosis-inducing genes during embryonic and larval development, we ablate most of the serotonergic neurons within the larval central nervous system. When testing these animals for naïve odor, sugar, salt and light perception, no profound phenotype was detectable; even appetitive and aversive learning was normal. Our results provide the first comprehensive description of the neuronal network of the larval serotonergic system. Moreover, they suggest that serotonin per se is not necessary for any of the behaviors tested. However, our data do not exclude that this system may modulate or fine-tune a wide set of behaviors, similar to its reported function in other insect species or in mammals. Based on our observations and the availability of a wide variety of genetic tools, this issue can now be addressed.

  12. The serotonergic central nervous system of the Drosophila larva: anatomy and behavioral function.

    Science.gov (United States)

    Huser, Annina; Rohwedder, Astrid; Apostolopoulou, Anthi A; Widmann, Annekathrin; Pfitzenmaier, Johanna E; Maiolo, Elena M; Selcho, Mareike; Pauls, Dennis; von Essen, Alina; Gupta, Tripti; Sprecher, Simon G; Birman, Serge; Riemensperger, Thomas; Stocker, Reinhard F; Thum, Andreas S

    2012-01-01

    The Drosophila larva has turned into a particularly simple model system for studying the neuronal basis of innate behaviors and higher brain functions. Neuronal networks involved in olfaction, gustation, vision and learning and memory have been described during the last decade, often up to the single-cell level. Thus, most of these sensory networks are substantially defined, from the sensory level up to third-order neurons. This is especially true for the olfactory system of the larva. Given the wealth of genetic tools in Drosophila it is now possible to address the question how modulatory systems interfere with sensory systems and affect learning and memory. Here we focus on the serotonergic system that was shown to be involved in mammalian and insect sensory perception as well as learning and memory. Larval studies suggested that the serotonergic system is involved in the modulation of olfaction, feeding, vision and heart rate regulation. In a dual anatomical and behavioral approach we describe the basic anatomy of the larval serotonergic system, down to the single-cell level. In parallel, by expressing apoptosis-inducing genes during embryonic and larval development, we ablate most of the serotonergic neurons within the larval central nervous system. When testing these animals for naïve odor, sugar, salt and light perception, no profound phenotype was detectable; even appetitive and aversive learning was normal. Our results provide the first comprehensive description of the neuronal network of the larval serotonergic system. Moreover, they suggest that serotonin per se is not necessary for any of the behaviors tested. However, our data do not exclude that this system may modulate or fine-tune a wide set of behaviors, similar to its reported function in other insect species or in mammals. Based on our observations and the availability of a wide variety of genetic tools, this issue can now be addressed.

  13. A review of nanoparticle functionality and toxicity on the central nervous system.

    Science.gov (United States)

    Yang, Z; Liu, Z W; Allaker, R P; Reip, P; Oxford, J; Ahmad, Z; Ren, G

    2010-08-06

    Although nanoparticles have tremendous potential for a host of applications, their adverse effects on living cells have raised serious concerns recently for their use in the healthcare and consumer sectors. As regards the central nervous system (CNS), research data on nanoparticle interaction with neurons has provided evidence of both negative and positive effects. Maximal application dosage of nanoparticles in materials to provide applications such as antibacterial and antiviral functions is approximately 0.1-1.0 wt%. This concentration can be converted into a liquid phase release rate (leaching rate) depending upon the host or base materials used. For example, nanoparticulate silver (Ag) or copper oxide (CuO)-filled epoxy resin demonstrates much reduced release of the metal ions (Ag(+) or Cu(2+)) into their surrounding environment unless they are mechanically removed or aggravated. Subsequent to leaching effects and entry into living systems, nanoparticles can also cross through many other barriers, such as skin and the blood-brain barrier (BBB), and may also reach bodily organs. In such cases, their concentration or dosage in body fluids is considered to be well below the maximum drug toxicity test limit (10(-5) g ml(-1)) as determined in artificial cerebrospinal solution. As this is a rapidly evolving area and the use of such materials will continue to mature, so will their exposure to members of society. Hence, neurologists have equal interests in nanoparticle effects (positive functionality and negative toxicity) on human neuronal cells within the CNS, where the current research in this field will be highlighted and reviewed.

  14. 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

    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...... reduction equalling a number needed to treat of 180. Sample size estimation is adjusted for the study design and based on standards for randomization on cluster-level. With an average cluster size of 2,500 patients, 70,000 patients will be enrolled over a 1-year trial period. The database is programmed so...

  15. Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770.

    Science.gov (United States)

    Gentzsch, Martina; Ren, Hong Y; Houck, Scott A; Quinney, Nancy L; Cholon, Deborah M; Sopha, Pattarawut; Chaudhry, Imron G; Das, Jhuma; Dokholyan, Nikolay V; Randell, Scott H; Cyr, Douglas M

    2016-09-01

    Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX-770 and corrector VX809 and is approved for treatment of CF patients homozygous for F508del, which has folding and gating defects. At least 30% of CF patients are heterozygous for the F508del mutation with the other allele encoding for one of many different rare CFTR mutations. Treatment of heterozygous F508del patients with VX-809 and VX-770 has had limited success, so it is important to identify heterozygous patients that respond to CFTR modulator therapy. R117H is a more prevalent rare mutation found in over 2,000 CF patients. In this study we investigated the effectiveness of VX-809/VX-770 therapy on restoring CFTR function in human bronchial epithelial (HBE) cells from R117H/F508del CF patients. We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. R117H expressed exclusively in immortalized HBEs exhibited a folding defect, was retained in the ER, and degraded prematurely. VX-809 corrected the R117H folding defect and restored channel function. Because R117 is involved in ion conductance, VX-770 acted additively with VX-809 to restore CFTR function in chronically treated R117H/F508del cells. Although treatment of R117H patients with VX-770 has been approved, our studies indicate that Orkambi may be more beneficial for rescue of CFTR function in these patients.

  16. Prenatal MRI Findings of Fetuses with Congenital High Airway Obstruction Sequence

    Energy Technology Data Exchange (ETDEWEB)

    Guimaraes, Carolina V. A.; Linam, Leann E.; Kline-Fath, Beth M. [Cincinnati Children' s Hospital Medical Center, Cincinnati (United States)] (and others)

    2009-04-15

    To define the MRI findings of congenital high airway obstruction sequence (CHAOS) in a series of fetuses. Prenatal fetal MR images were reviewed in seven fetuses with CHAOS at 21 to 27 weeks of gestation. The MRI findings were reviewed. The MRI parameters evaluated included the appearance of the lungs and diaphragm, presence or absence of hydrops, amount of amniotic fluid, airway appearance, predicted level of airway obstruction, and any additional findings or suspected genetic syndromes. All the fetuses viewed (7 of 7) demonstrated the following MRI findings: dilated airway below the level of obstruction, increased lung signal, markedly increased lung volumes with flattened or inverted hemidiaphragms, massive ascites, centrally positioned and compressed heart, as well as placentomegaly. Other frequent findings were anasarca (6 of 7) and polyhydramnios (3 of 7). MRI identified the level of obstruction as laryngeal in five cases and tracheal in two cases. In four of the patients, surgery or autopsy confirmed the MRI predicted level of obstruction. Associated abnormalities were found in 4 of 7 (genetic syndromes in 2). Postnatal radiography (n = 3) showed markedly hyperinflated lungs with inverted or flattened hemidiaphragms, strandy perihilar opacities, pneumothoraces and tracheotomy. Two fetuses were terminated and one fetus demised in utero. Four fetuses were delivered via ex utero intrapartum treatment procedure. MRI shows a consistent pattern of abnormalities in fetuses with CHAOS, accurately identifies the level of airway obstruction, and helps differentiate from other lung abnormalities such as bilateral congenital pulmonary airway malformation by demonstrating an abnormally dilated airway distal to the obstruction.

  17. Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

    Lo, P.; Sporring, J.; Ashraf, H.;

    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...... method is evaluated on 250 low dose computed tomography images from a lung cancer screening trial. Our experiments showed that applying the region growing algorithm on the airway appearance model produces more complete airway segmentations, leading to on average 20% longer trees, and 50% less leakage...

  18. Inflammatory bowel disease and airway diseases

    Science.gov (United States)

    Vutcovici, Maria; Brassard, Paul; Bitton, Alain

    2016-01-01

    Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact. PMID:27678355

  19. Mucus hypersecretion in the airway

    Institute of Scientific and Technical Information of China (English)

    WANG Ke; WEN Fu-qiang; XU Dan

    2008-01-01

    @@ Mucus hypersecretion is a distinguishing feature of Chronic intlammation diseases,such as asthma,1chronic bronchitis.2 bronchiectasis3 and cystic fibrosis.4Mucus hypersecretion leads to impairment of mucociliary clearance,abnormal bacterial plantation,mucus plug in the airway,and dysfunction of gas exchange.5

  20. Nasal continuous positive airway pressure

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Lamwers, Stephanie; Tepel, Martin;

    2012-01-01

    Obstructive sleep apnoea (OSA) is linked to increased cardiovascular risk. This risk can be reduced by nasal continuous positive airway pressure (nCPAP) treatment. As OSA is associated with an increase of several vasoconstrictive factors, we investigated whether nCPAP influences the digital volum...

  1. Airway nerves: in vitro electrophysiology.

    Science.gov (United States)

    Fox, Alyson

    2002-06-01

    Recording the activity of single airway sensory fibres or neuronal cell bodies in vitro has allowed detailed characterisation of fibre types and membrane properties. Fibre types can be identified by their conduction velocities and further studied by the application of drugs to their receptive field. C-fibres are sensitive to mechanical stimuli and a range of irritant chemicals (bradykinin, capsaicin, low pH, platelet-activating factor), whereas Adelta-fibres are relatively insensitive to chemical stimuli and appear to correlate to the rapidly adapting receptors identified in airways in vivo. Their site of origin also differs: upper airway C-fibres arise predominantly from the jugular ganglion and Adelta-fibres from the jugular and nodose ganglia. Intracellular recording from cell bodies in the ganglia has revealed a calcium-dependent potassium current common to many putative C-fibre cell bodies. This slow after hyperpolarisation current may be inhibited by stimuli that excite and sensitise C-fibres - this could be an important mechanism underlying the sensitisation of C-fibres in airway irritability.

  2. Clinical research of cryotherapy and balloon dilation for severe benign central airway stenosis through laryngeal mask%喉罩通气下冷冻联合球囊扩张治疗严重良性中央气道狭窄的临床研究

    Institute of Scientific and Technical Information of China (English)

    史小武; 赵苏

    2014-01-01

    目的:观察喉罩通气下经电子支气管镜冷冻联合球囊扩张治疗严重良性气道狭窄的近、远期疗效和安全性。方法选取2011年1月至2013年12月严重良性中央气道狭窄的患者45例,在喉罩通气下给予冷冻联合球囊扩张治疗,比较治疗前后气道直径、一秒用力呼气容积(FEV1)、Hugh-Jones分级、血氧分压(PaO2)和生活质量评分等指标的变化,并随访治疗的近、远期疗效和并发症。结果经过3~8个疗程治疗后,气道直径、FEV1、Hugh-Jones分级、PaO2和生活质量评分等指标有明显改善(P<0.05)。45例患者中38例(84.4%)缓解良好,狭窄部位气管内径达到原气管内径50%以上,肺叶完全复张;7例(15.6%)缓解良好,肺叶部分复张。近期不良反应:咽痛、咳嗽11例(22.4%),出血17例(37.8%),气胸2例(4.4%);随访18个月远期效果:5例(11.1%)患者出现再狭窄(平均2.5个月),给予冷冻及球囊扩张治疗后缓解。结论喉罩通气下冷冻联合球囊扩张治疗严重良性气道狭窄效果显著、安全性高、疗效确切,值得推广。%Objective To observe the short- and long-term efficacy and safety of cryotherapy and balloon dilation for severe benign central airway stenosis through laryngeal mask.Methods Forty-five patients with severe benign central airway stenosis were envolved from January 2011 to December 2013.The patients were treated with cryotherapy and balloon dilation under general anesthesia through laryngeal mask.The airway diameter,forced expiratory volume in one second (FEV1 ),Hugh-Jones classification,partial pressure of oxygen (PaO2 )and quality of life scores were compared before and after treatment.The short-and long-term efficacy and complications were followed up.Results After three to eigth courses of treatment,airway diameter,FEV1 ,Hugh-Jones classification,PaO2 and quality of life

  3. On the existence and function of galanin receptor heteromers in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-10-01

    Full Text Available Galanin receptor (GalR subtypes1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein coupled receptors (GPCRs in the Central Nervous System (CNS. These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15 to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1-5-HT1A heteromers in cellular models with transinhibition of the protomer signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15 in the CNS. Furthermore, a GalR1-GalR2-5-HT1A heterotrimer is postulated to explain why only galanin (1-15 but not galanin (1-29 can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1-GalR2 heteromer appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer. Finally, putative GalR-α2-adrenoreceptor heteromers with antagonistic receptor-receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression.

  4. Effects of obesity and weight loss on airway physiology and inflammation in asthma.

    Science.gov (United States)

    Sideleva, Olga; Black, Kendall; Dixon, Anne E

    2013-08-01

    Obesity is a major risk factor for asthma, but the mechanisms for the development of asthma in the setting of obesity are not known. The purpose of this article is to review the effects of obesity on airway inflammation in patients with asthma, and to discuss the effects of obesity on airway reactivity in patients with asthma. Obesity is particularly a risk factor for non-atopic asthma. Airway eosinophilic inflammation is not increased in obesity, in fact the preponderance of the evidence suggests that airway eosinophilia is decreased in obesity. There is some preliminary data suggesting that airway neutrophilia may be increased in obesity, and that this may be particularly related to dietary fats. Obesity also alters adaptive immunity, and may suppress lymphocyte function typically associated with asthmatic airway inflammation. Population based studies are somewhat inconsistent on the relationship between airway reactivity and asthma, however, recent studies in bariatric surgery show that weight loss surgery in severely obese patients decreases airway reactivity. One study suggested that this was particularly the case for those with low IgE (a marker of a low TH2 asthma phenotype), suggesting there may be some heterogeneity in asthma in obesity. There are likely to be two phenotypes of asthma in the obese: one group with early onset disease and asthma complicated by obesity, and a 2nd group with late onset disease with asthma consequent to obesity. Obesity leads to profound changes in airway function, and adaptive and innate immune responses which alter the nature of pre-existing allergic airway disease, and also cause new onset asthmatic disease.

  5. Observations of Adolescent Peer Group Interactions as a Function of Within- and Between-Group Centrality Status

    Science.gov (United States)

    Ellis, Wendy E.; Dumas, Tara M.; Mahdy, Jasmine C.; Wolfe, David A.

    2012-01-01

    Observations of adolescent (n = 258; M age = 15.45) peer group triads (n = 86) were analyzed to identify conversation and interaction styles as a function of within-group and between-group centrality status. Group members' discussions about hypothetical dilemmas were coded for agreements, disagreements, commands, and opinions. Interactions during…

  6. Up-Regulation of Endothelin Receptors Induced by Cigarette Smoke — Involvement of MAPK in Vascular and Airway Hyper-Reactivity

    Directory of Open Access Journals (Sweden)

    Yaping Zhang

    2010-01-01

    Full Text Available Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to endothelin-1 (ET-1, endothelin receptor agonist in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm and adverse proliferation (remodeling of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen-activated protein kinase (MAPK and subsequently results in the up-regulation of endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette smoke causes up-regulation of endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette smoke—associated cardiovascular and lung diseases.

  7. Excessive dynamic airway collapse in a small cohort of chronic obstructive pulmonary disease patients

    Directory of Open Access Journals (Sweden)

    C Represas-Represas

    2015-01-01

    The percentage of collapse at each anatomic level was as follows: Aortic arch, 16.1% (SD, 13.6%; carina, 19.4% (SD, 15.9%; and bronchus intermedius, 21.7% (SD, 16.1%. At the point of maximal collapse, the percentage of collapse was 26.8% (SD, 16%. EDAC was demonstrated at any of the three anatomical points in five patients, corresponding to 9.4% (95% CI, 3.1% to 20.6% of the sample and affecting the three anatomical points in only two cases. A statistically significant correlation was only found with the total lung capacity (TLC. CONCLUSIONS: The prevalence of EDAC observed in a sample of patients with different levels of COPD severity is low. The degree of dynamic central airway collapse was not related to the patient′s epidemiological or clinical features, and did not affect lung function, symptoms, capacity for effort, or quality of life.

  8. Topography and function of androgen-metabolizing enzymes in the central nervous system.

    Science.gov (United States)

    Tsuruo, Yoshihiro

    2005-03-01

    The present review describes concisely the topography and function of the three androgen-metabolizing enzymes, namely aromatase, 5alpha-reductase and 3alpha-hydroxysteroid dehydrogenase, in the central nervous system (CNS). Aromatase, estrogen synthetase, is the key enzyme for converting androgens to estrogens. Aromatase is indispensable for the sexual differentiation of the brain and the enzyme activity and expression of aromatase are high during the critical period of neural development, which extends from the late embryonal to the early neonatal period in rodents. Aromatase is expressed in neurons within specific hypothalamic and limbic regions. The locations of aromatase-immunoreactive neurons are divided into three groups according to the period of enzyme expression. Steroid 5alpha-reductase converts a number of steroids with a C3 ketone group and a C4-C5 double bond (delta4; androgens, progestins and glucocorticoids) to their 5alpha-reduced metabolites. Two isoforms of 5alpha-reductase are found and type 1 is predominant in neural tissues. The enzyme activity of 5alpha-reductase is found widely in the CNS and is high in white matter regions. The enzyme expression of 5alpha-reductase peaks during the late embryonic period. 3alpha-Hydroxysteroid dehydrogenase is the oxidoreductase that interconverts 3-ketosteroids to 3alpha-hydroxysteroids. Four isozymes have been found in humans and only one type has been found in rats. The enzyme converts 5alpha-reduced steroids (e.g. 5alpha-dihydroprogesterone) to tetrahydrosteroids (e.g. 3alpha,5alpha-tetrahydroprogesterone). The latter steroid is a potent stimulator of the GABA(A) receptor. The activity of 3alpha-hydroxysteroid dehydrogenase is high during the first 1-2 postnatal weeks, decreases with development and this enzyme is highly expressed in astrocytes.

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

    Directory of Open Access Journals (Sweden)

    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

  10. A pathogenic role for the integrin CD103 in experimental allergic airways disease.

    Science.gov (United States)

    Fear, Vanessa S; Lai, Siew Ping; Zosky, Graeme R; Perks, Kara L; Gorman, Shelley; Blank, Fabian; von Garnier, Christophe; Stumbles, Philip A; Strickland, Deborah H

    2016-11-01

    The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4(+) T-cell activation and DC activation and function in airways and lymph nodes. We found reduced airways hyper-responsiveness and eosinophil recruitment to airways after aerosol challenge of CD103 KO compared to wild-type (WT) mice, although CD103 KO mice showed enhanced serum OVA-specific IgE levels. Following aerosol challenge, total numbers of effector and regulatory CD4(+) T-cell subsets were significantly increased in the airways of WT but not CD103 KO mice, as well as a lack of DC recruitment into the airways in the absence of CD103. While total airway DC numbers, and their in vivo allergen capture activity, were essentially normal in steady-state CD103 KO mice, migration of allergen-laden airway DC to draining lymph nodes was disrupted in the absence of CD103 at 24 h after aerosol challenge. These data support a role for CD103 in the pathogenesis of EAAD in BALB/c mice through local control of CD4(+) T cell and DC subset recruitment to, and migration from, the airway mucosa during induction of allergic inflammation.

  11. Central limit theorem of nonparametric estimate of spectral density functions of sample covariance matrices

    CERN Document Server

    Pan, Guangming; Zhou, Wang

    2010-01-01

    A consistent kernel estimator of the limiting spectral distribution of general sample covariance matrices was introduced in Jing, Pan, Shao and Zhou (2010). The central limit theorem of the kernel estimator is proved in this paper.

  12. An exploration of central dysregulation of erectile function as a contributing cause of diabetic impotence.

    Science.gov (United States)

    Nofzinger, E A; Schmidt, H S

    1990-02-01

    Diabetic impotence is generally presumed to be secondary to peripheral abnormalities of the vascular or autonomic nervous system, although central nervous control of the autonomic nervous system has not previously been studied. Measures of rapid eye movement (REM) sleep as potential indicators of central autonomic dysfunction were studied along with sleep-related tumescence for 10 impotent diabetics, nine psychogenically impotent men, and 10 men whose impotence was secondary to pelvic trauma. Low REM density was found in the diabetics with REM density correlating with measures of tumescence. These results suggest that central autonomic dysfunction may be a contributing factor in the impotence of diabetic men. A metabolic disturbance in the central nervous system of diabetics which might alter both sleep and autonomic nervous system activity is proposed to explain these results and may help in the understanding of other observed abnormalities in both the sleep and autonomic dysfunction of diabetics.

  13. Cold air challenge and specific airway resistance in preschool children

    DEFF Research Database (Denmark)

    Nielsen, Kim Gjerum; Bisgaard, Hans

    2005-01-01

    prognosis in preschool children. Cold air challenge and plethysmographic measurement of specific airway resistance (sRaw) are feasible candidate methods for diagnosis, clinical monitoring and research during this critical period of lung growth and development. Methodology and practical aspects of cold air......Important asthma outcomes such as lung function and bronchial hyperresponsiveness are probably determined in early childhood. Early and longitudinal objective assessment of lung function and bronchial hyperresponsiveness is necessary to enable early diagnosis, monitor intervention and improve...

  14. Hypoxia Potentiates Allergen Induction of HIF-1α, Chemokines, Airway Inflammation, TGF-β1, and Airway Remodeling in a mouse model

    Science.gov (United States)

    Baek, Kwang Je; Cho, Jae Youn; Rosenthal, Peter; Alexander, Laura E. Crotty; Nizet, Victor; Broide, David H.

    2013-01-01

    Whether hypoxia contributes to airway inflammation and remodeling in asthma is unknown. In this study we used mice exposed to a hypoxic environment during allergen challenge (simulating hypoxia during an asthma exacerbation) to investigate the contribution of hypoxia to airway inflammation and remodeling. Although neither hypoxia alone, nor OVA allergen alone, induced significant neutrophil influx into the lung, the combination of OVA and hypoxia induced a synergistic 27 fold increase in peribronchial neutrophils, enhanced expression of HIF-1α and one of its target genes, the CXC-family neutrophil chemokine KC. The combination of hypoxia and OVA allergen increased eotaxin-1, peribronchial eosinophils, lung TGB-β1 expression, and indices of airway remodeling (fibrosis and smooth muscle) compared to either stimulus alone. As hypoxia is present in >90% of severe asthma exacerbations, these findings underscore the potential of hypoxia to potentiate the airway inflammatory response, remodeling, and accelerate the decline of lung function in asthma exacerbations. PMID:23499929

  15. Narrowing of the balance function with centrality in Au + Au collisions at √(sNN)

    Energy Technology Data Exchange (ETDEWEB)

    Adams, J.; Alder, C.; Ahammed, Z.; Allgower, C.; Amonett, J.; Anderson, B. D.; Anderson, M.; Averichev, G. S.; Balewski, J.; Barannikova, O.; Barnby, L. S.; Baudot, J.; Bekele, S.; Belaga, V. V.; Bellwied, R.; Berger, J.; Bichsel, H.; Billmeier, A.; Bland, L. C.; Blyth, C. O.; Bonner, B. E..; Boucham, A.; Brandin, A.; Bravar, A.; Cadman, R. V.; Caines, H.; Cardenas, A.; Carroll, J.; Castillo, J.; Castro, M.; Cebra, D.; Chaloupka, P.; Chattopadhyay, S.; Chen, Y.; Chernenko, S. P.; Cherney, M.; Chikanian, A.; Choi, B.; Christie, W.; Coffin, J. P.; Cormier, T. M.; Corral, M. M.; Cramer, J. G.; Crawford, H. J.; Derevschikov, A. A.; Didenko, L.; Dietel, T.; Draper, J. E.; Dunin, V. B.; Dunlop, J. C.; Eckardt, V.; Efimov, L. G.; Emelianov, V.; Engelage, J.; Eppley, G.; Erazmus, B.; Fachini, P.; Faine, V.; Faivre, J.; Fatemi, R.; Filimonov, K.; Finch, E.; Fisyak, Y.; Flierl, D.; Foley, K.. J; Fu, J..; Gagliardi, C. A.; Gagunashvili, N.; Gans, J.; Gaudichet, L.; Germain, M.; Geurts, F.; Ghazikhanian, V.; Grachov, O.; Grigoriev, V.; Guedon, M.; Guertin, S. M.; Gushin, E.; Hallman, T. J.; Hardtke, D.; Harris, J. W.; Heinz, M.; Henry, T. W.; Heppelmann, S.; Herston, T.; Hippolyte, B.; Hirsch, A.; Hjort, E.; Hoffmann, G. W.; Horsley, M.; Huang, H. Z.; Humanic, T. J.; Igo, G.; Ishihara, A.; Ivanshin, Yu I.; Jacobs, P.; Jacobs, W. W.; Janik, M.; Johnson, I.; Jones, P. G.; Judd, E. G.; Kaneta, M.; Kaplan, M.; Keane, D.; Kiryluk, J.; Kisiel, A.; Klay, J.; Klein, S. R.; Klyachko, A.; Kollegger, T.; Konstantinov, A. S.; Kopytine, M.; Kotchenda, L.; Kovalenko, A. D.; Kramer, M.; Kravtsov, P.; Krueger, K.; Kuhn, C.; Kulikov, A. I; Kunde, G. J.; Kunz, C. L.; Kutuev, R. Kh; Kuznetsov, A. A.; Lamont, M. A.C.; Landgraf, J. M..; Lange, S.; Lansdell, C. P.; Lasiuk, B.; Laue, F.; Lauret, J.; Lebedev, A.; Lednicky, R.; Leontiev, V. M.; LeVine, M. J.; Li, Q.; Lindenbaum, S. J.; Lisa, M. A.; Liu, F.; Liu, L.; Liu, Z.; Liu, Q. J.; Ljubicic, T.; Llope, W. J.; Long, H. [et al.

    2003-05-01

    The balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au + Au collisions at √(sNN) = 130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering. Widths in central collisions are smaller, consistent with trends predicted by models incorporating late hadronization.

  16. The Structure of the Mantle Lithosphere in Central Europe from S-Receiver Functions

    Science.gov (United States)

    Kind, Rainer; Handy, Mark; Yuan, Xiaohui; Meier, Thomas

    2016-04-01

    Data from about 650 permanent and temporary seismic broadband stations accessed from the open EIDA Archive yielded about 49.000 S-receiver functions. Selection criteria were a signal-to-noise ratio of at least two of the S signal on the SV component, low noise on the P component before the S arrival time and a relatively good approximation of the delta im- pulse on the SV component after deconvolution. All traces were checked visually. The time domain traces were migrated to depth domain by back projection along the ray path. Smooth images of major discontinuities in the upper mantle were obtained by applying an eight-seconds low-pass filter. Observations of the Moho and the discontinuity at 410 km depth serve as a check of the quality of the analysis. We observe two widespread negative (i.e., downward reduction in velocity) discontinuities. The shallower one in about the 50 km to 150 km depth interval occurs everywhere in the study area and is interpreted as the lithosphere-asthenosphere boundary (LAB) in Phanerozoic Europe. According to similar observations in the north American craton, it is interpreted as mid-lithospheric discontinuity (MLD) in the east European craton (EEC). The second negative discontinuity seen beneath the EEC, the Trans-European Suture Zone, the Bohemian Massive, and parts of the Pannonian Basin lies at a depth interval of about 150 km to 300 km. It is interpreted as cratonic LAB reaching well the S and E of the Torn- quist-Teisseyre Zone, which is considered the boundary of the EEC at the shallower levels. The deeper cratonic LAB has anomalous topography: Below the Pannonian Basin it shal- lows to c. 150 km but deepens to c. 300 km below the Bohemian Massif. There is a jump in the cratonic LAB along the northern edge of the Bohemian Massif, where the LAB sud- denly changes depth from 200 km in the north to 300 km in the south. We tentatively inter- pret these observations as a result of overthrusting the EEC mantle lithosphere during the

  17. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hansel, Nadia N.; Pare, Peter D.; Rafaels, Nicholas; Sin, Don D.; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W. Mark; Pascoe, Chris D.; Arsenault, Bryna A.; Postma, Dirkje S.; Boezen, Marieke H.; Bosse, Yohan; van den Berge, Maarten; Hiemstra, Pieter S.; Cho, Michael H.; Litonjua, Augusto A.; Sparrow, David; Ober, Carole; Wise, Robert A.; Connett, John; Neptune, Enid R.; Beaty, Terri H.; Ruczinski, Ingo; Mathias, Rasika A.; Barnes, Kathleen C.

    2015-01-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina

  18. 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.

  19. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction.

    Science.gov (United States)

    Perez, Thierry; Chanez, Pascal; Dusser, Daniel; Devillier, Philippe

    2013-11-01

    Asthma is a disease characterized by inflammation which affects both proximal and distal airways. We evaluated the prevalence of small airway obstruction (SAO) in a group of clinically stable asthmatics with both normal forced expiratory volume in the first second (FEV1) and normal FEV1/forced vital capacity (FVC) and treated with an association of inhaled corticosteroids (ICSs) and long acting β2-agonists (LABAs). Clinical evaluation included the measurement of dyspnea, asthma control test and drug compliance. The prevalence of SAO was estimated by spirometry and plethysmography and defined by the presence of one or more of the following criteria: functional residual capacity (FRC) > 120% predicted (pred), residual volume (RV) > pred + 1.64 residual standard deviation (RSD), RV/total lung capacity (TLC) > pred + 1.64 RSD, forced expiratory flow (FEF)25-75% slow vital capacity (SVC) - FVC > 10%. Among the 441 patients who were included, 222 had normal FEV1 and FEV1/FVC. At least one criteria of SAO was found in 115 (52%) mainly lung hyperinflation (39% based on high FRC, RV or RV/TLC) and more rarely distal airflow limitation (15% based on FEF25-75% or FEF50%) or expiratory trapping (10% based on increased SVC - FVC). In the patients with only SAO (no PAO), there was no relationship between SAO, asthma history and the scores of dyspnea, asthma control or drug compliance. These results suggest that in asthmatics with normal FEV1 and FEV1/FVC, treated with ICSs and LABAs, SAO is found in more than half of the patients indicating that the routinely used lung function tests can underestimate dysfunctions occurring in the small airways.

  20. Physiological Mechanisms of Airway Hyperresponsiveness in Obese Asthma.

    Science.gov (United States)

    Bates, Jason H T

    2016-05-01

    Obesity affects the incidence and severity of asthma in at least two major phenotypes: an early-onset allergic (EOA) form that is complicated by obesity and a late-onset nonallergic (LONA) form that occurs only in the setting of obesity. Both groups exhibit airway hyperresponsiveness to methacholine challenge but exhibit differential effects of weight loss. Measurements of lung function in patients with LONA obese asthma suggest that this group of individuals may simply be those unlucky enough to have airways that are more compliant than average, and that this leads to airway hyperresponsiveness at the reduced lung volumes caused by excess adipose tissue around the chest wall. In contrast, the frequent exacerbations in those with EOA obese asthma can potentially be explained by episodic inflammatory thickening of the airway wall synergizing with obesity-induced reductions in lung volume. These testable hypotheses are based on the strong likelihood that LONA and EOA obese asthma are distinct diseases. Both, however, may benefit from targeted therapeutics that impose elevations in lung volume.

  1. Organization and functional roles of the central complex in the insect brain.

    Science.gov (United States)

    Pfeiffer, Keram; Homberg, Uwe

    2014-01-01

    The central complex is a group of modular neuropils across the midline of the insect brain. Hallmarks of its anatomical organization are discrete layers, an organization into arrays of 16 slices along the right-left axis, and precise inter-hemispheric connections via chiasmata. The central complex is connected most prominently with the adjacent lateral complex and the superior protocerebrum. Its developmental appearance corresponds with the appearance of compound eyes and walking legs. Distinct dopaminergic neurons control various forms of arousal. Electrophysiological studies provide evidence for roles in polarized light vision, sky compass orientation, and integration of spatial information for locomotor control. Behavioral studies on mutant and transgenic flies indicate roles in spatial representation of visual cues, spatial visual memory, directional control of walking and flight, and place learning. The data suggest that spatial azimuthal directions (i.e., where) are represented in the slices, and cue information (i.e., what) are represented in different layers of the central complex.

  2. Chronic upper airway obstruction: value of the flow volume loop examination in assessment and management.

    Science.gov (United States)

    Brookes, G B; Fairfax, A J

    1982-06-01

    Chronic obstructive lesions of the upper airways such as post-traumatic strictures, bilateral vocal cord paralysis and chronic inflammatory foci are uncommon. The functional assessment of the severity and character of an obstruction is important both for diagnosis and management, and may also allow evaluation of the efficacy of medical and surgical treatment. There are limitations of simple spirometric pulmonary function tests, which are evident when assessing upper airways obstruction. The flow volume loop is a graphic recording of airflow during maximal respiration and expiration at different lung volumes, and may be affected in a characteristic way by alterations in the airway resistance. Three unusual cases of chronic upper airway obstruction are presented which illustrate the value of the flow volume loop examination in their management.

  3. Method for 3D Airway Topology Extraction

    Directory of Open Access Journals (Sweden)

    Roman Grothausmann

    2015-01-01

    Full Text Available In lungs the number of conducting airway generations as well as bifurcation patterns varies across species and shows specific characteristics relating to illnesses or gene variations. A method to characterize the topology of the mouse airway tree using scanning laser optical tomography (SLOT tomograms is presented in this paper. It is used to test discrimination between two types of mice based on detected differences in their conducting airway pattern. Based on segmentations of the airways in these tomograms, the main spanning tree of the volume skeleton is computed. The resulting graph structure is used to distinguish between wild type and surfactant protein (SP-D deficient knock-out mice.

  4. Anatomic Optical Coherence Tomography of Upper Airways

    Science.gov (United States)

    Chin Loy, Anthony; Jing, Joseph; Zhang, Jun; Wang, Yong; Elghobashi, Said; Chen, Zhongping; Wong, Brian J. F.

    The upper airway is a complex and intricate system responsible for respiration, phonation, and deglutition. Obstruction of the upper airways afflicts an estimated 12-18 million Americans. Pharyngeal size and shape are important factors in the pathogenesis of airway obstructions. In addition, nocturnal loss in pharyngeal muscular tone combined with high pharyngeal resistance can lead to collapse of the airway and periodic partial or complete upper airway obstruction. Anatomical optical coherence tomography (OCT) has the potential to provide high-speed three-dimensional tomographic images of the airway lumen without the use of ionizing radiation. In this chapter we describe the methods behind endoscopic OCT imaging and processing to generate full three dimensional anatomical models of the human airway which can be used in conjunction with numerical simulation methods to assess areas of airway obstruction. Combining this structural information with flow dynamic simulations, we can better estimate the site and causes of airway obstruction and better select and design surgery for patients with obstructive sleep apnea.

  5. AIRWAY VISUALIZATION: EYES SEE WHAT MIND KNOWS.

    Science.gov (United States)

    Sorbello, Massimiliano; Frova, Giulio; Zdravković, Ivana

    2016-03-01

    Airway management is basic for anesthesia practice, and sometimes it can represent a really dramatic scenario for both the patient and the physicians. Laryngoscopy has been the gold standard of airway visualization for more than 60 years, showing its limitations and failure rates with time. New technology has made available an opportunity to move the physician's eye inside patient airways thanks to video laryngoscopy and video assisted airway management technique. Undoubtedly, we have entered a new era of high resolution airway visualization and different approach in airway instrumentation. Nevertheless, each new technology needs time to be tested and considered reliable, and pitfalls and limitations may come out with careful and long lasting analysis, so it is probably not the right time yet to promote video assisted approach as a new gold standard for airway visualization, despite the fact that it certainly offers some new prospects. In any case, whatever the visualization approach, no patient dies because of missed airway visualization or failed intubation, but due to failed ventilation, which remains without doubt the gold standard of any patient safety goal and airway management technique.

  6. Ultrasonography in the management of the airway

    DEFF Research Database (Denmark)

    Kristensen, M S

    2011-01-01

    In this study, it is described how to use ultrasonography (US) for real-time imaging of the airway from the mouth, over pharynx, larynx, and trachea to the peripheral alveoli, and how to use this in airway management. US has several advantages for imaging of the airway - it is safe, quick...... or the esophagus by placing the ultrasound probe transversely on the neck at the level of the suprasternal notch during intubation, thus confirming intubation without the need for ventilation or circulation. US can be applied before anesthesia induction and diagnose several conditions that affect airway management...

  7. Pim1 kinase protects airway epithelial cells from cigarette smoke-induced damage and airway inflammation

    NARCIS (Netherlands)

    de Vries, M.; Heijink, Hilde; Gras, R.; den Boef, L. E.; Reinders-Luinge, M.; Pouwels, S. D.; Hylkema, Machteld; van der Toorn, Marco; Brouwer, U.; van Oosterhout, A. J. M.; Nawijn, M. C.

    2014-01-01

    Exposure to cigarette smoke (CS) is the main risk factor for developing chronic obstructive pulmonary disease and can induce airway epithelial cell damage, innate immune responses, and airway inflammation. We hypothesized that cell survival factors might decrease the sensitivity of airway epithelial

  8. REVIEW ARTICLE: In vivo magnetic resonance imaging: insights into structure and function of the central nervous system

    Science.gov (United States)

    Natt, Oliver; Frahm, Jens

    2005-04-01

    Spatially resolved nuclear magnetic resonance (NMR) techniques provide structural, metabolic and functional insights into the central nervous system and allow for repetitive in vivo studies of both humans and animals. Complementing its prominent role in diagnostic imaging, magnetic resonance imaging (MRI) has evolved into an indispensable research tool in system-oriented neurobiology where contributions to functional genomics and translational medicine bridge the gap from molecular biology to animal models and clinical applications. This review presents an overview on some of the most relevant advances in MRI. An introduction covering the basic principles is followed by a discussion of technological improvements in instrumentation and imaging sequences including recent developments in parallel acquisition techniques. Because MRI is noninvasive in contrast to most other imaging modalities, examples focus on in vivo studies of the central nervous system in a variety of species ranging from humans to mice and insects.

  9. Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle.

    Science.gov (United States)

    Calkovska, A; Uhliarova, B; Joskova, M; Franova, S; Kolomaznik, M; Calkovsky, V; Smolarova, S

    2015-04-01

    Beside alveoli, surface active material plays an important role in the airway physiology. In the upper airways it primarily serves in local defense. Lower airway surfactant stabilizes peripheral airways, provides the transport and defense, has barrier and anti-edematous functions, and possesses direct relaxant effect on the smooth muscle. We tested in vitro the effect of two surfactant preparations Curosurf® and Alveofact® on the precontracted smooth muscle of intra- and extra-pulmonary airways. Relaxation was more pronounced for lung tissue strip containing bronchial smooth muscle as the primary site of surfactant effect. The study does not confirm the participation of ATP-dependent potassium channels and cAMP-regulated epithelial chloride channels known as CFTR chloride channels, or nitric oxide involvement in contractile response of smooth muscle to surfactant.By controlling wall thickness and airway diameter, pulmonary surfactant is an important component of airway physiology. Thus, surfactant dysfunction may be included in pathophysiology of asthma, COPD, or other diseases with bronchial obstruction.

  10. Structur e and Functioning of Micr obial Community of Mineral Springs in Central Asia

    Directory of Open Access Journals (Sweden)

    Namsaraev B.B.

    2003-12-01

    Full Text Available The microbial mats of dif ferent types of springs in Central Asia (Zabaikalye and Mongolia are described. The species diversity of mat-formed phototrophic bacteria was determined. The rates of microbial destruction processes (sulfate reduction and methane formation were measured. An important role of bacteria and algae in the formation of mineral water composition was shown.

  11. A Functional Central Limit Theorem for a Class of Urn Models

    Indian Academy of Sciences (India)

    Gopal K Basak; Amites Dasgupta

    2005-11-01

    We construct an independent increments Gaussian process associated to a class of multicolor urn models. The construction uses random variables from the urn model which are different from the random variables for which central limit theorems are available in the two color case.

  12. The Central Information Services Function in County Governments: From Controller to Enabler.

    Science.gov (United States)

    Fletcher, Patricia T.; Bertot, John Carlo

    1994-01-01

    Discussion of the role of county government regarding the management of information technology focuses on a national study of the centralized management of information technology that was conducted to identify practices; assess benefits, costs, and constraints; enumerate critical success factors; and identify future challenges. (Contains 12…

  13. Myofibroblast expression in airways and alveoli is affected by smoking and COPD

    OpenAIRE

    Karvonen, Henna M; Lehtonen, Siri T.; Harju, Terttu; Sormunen, Raija T.; Lappi-Blanco, Elisa; Mäkinen, Johanna M.; Laitakari, Kirsi; Johnson, Shirley; Kaarteenaho, Riitta L.

    2013-01-01

    Background Chronic obstructive pulmonary disease (COPD) is characterized by structural changes in alveoli and airways. Our aim was to analyse the numbers of alpha-smooth muscle actin (α-SMA) positive cells, as a marker of myofibroblasts, in different lung compartments in non-smokers and smokers with normal lung function or COPD. Methods α-SMA, tenascin-C (Tn-C) and EDA-fibronectin in alveolar level and airways were assayed by immunohistochemistry and quantified by image analysis. Immunohistoc...

  14. Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13

    Directory of Open Access Journals (Sweden)

    Siddiqui Salman

    2010-07-01

    Full Text Available Abstract Background During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma. Method Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL samples from healthy subjects and those with asthma. Results PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL-13 and tumor necrosis factor (TNFα stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL fluid derived from healthy subjects as well as from those with asthma. Conclusion Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a

  15. Abnormal Intrinsic Functional Hubs in Severe Male Obstructive Sleep Apnea: Evidence from a Voxel-Wise Degree Centrality Analysis

    Science.gov (United States)

    Shao, Yi; Gong, Honghan; Zhang, Wei; Zeng, Xianjun; Ye, Chenglong; Nie, Si; Chen, Liting; Peng, Dechang

    2016-01-01

    Purpose Obstructive sleep apnea (OSA) has been associated with changes in brain structure and regional function in certain brain areas. However, the functional features of network organization in the whole brain remain largely uncertain. The purpose of this study was to identify the OSA-related spatial centrality distribution of the whole brain functional network and to investigate the potential altered intrinsic functional hubs. Methods Forty male patients with newly confirmed severe OSA on polysomnography, and well-matched good sleepers, participated in this study. All participants underwent a resting-state functional MRI scan and clinical and cognitive evaluation. Voxel-wise degree centrality (DC) was measured across the whole brain, and group difference in DC was compared. The relationship between the abnormal DC value and clinical variables was assessed using a linear correlation analysis. Results Remarkably similar spatial distributions of the functional hubs (high DC) were found in both groups. However, OSA patients exhibited a pattern of significantly reduced regional DC in the left middle occipital gyrus, posterior cingulate cortex, left superior frontal gyrus, and bilateral inferior parietal lobule, and DC was increased in the right orbital frontal cortex, bilateral cerebellum posterior lobes, and bilateral lentiform nucleus, including the putamen, extending to the hippocampus, and the inferior temporal gyrus, which overlapped with the functional hubs. Furthermore, a linear correlation analysis revealed that the DC value in the posterior cingulate cortex and left superior frontal gyrus were positively correlated with Montreal cognitive assessment scores, The DC value in the left middle occipital gyrus and bilateral inferior parietal lobule were negatively correlated with apnea-hypopnea index and arousal index in OSA patients. Conclusion Our findings suggest that OSA patients exhibited specific abnormal intrinsic functional hubs including relatively

  16. MiR-221 and miR-130a regulate lung airway and vascular development.

    Directory of Open Access Journals (Sweden)

    Sana Mujahid

    Full Text Available Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung.

  17. Airway surface liquid volume expansion induces rapid changes in amiloride-sensitive Na+ transport across upper airway epithelium-Implications concerning the resolution of pulmonary edema

    Science.gov (United States)

    Azizi, Fouad; Arredouani, Abdelilah; Mohammad, Ramzi M

    2015-01-01

    During airway inflammation, airway surface liquid volume (ASLV) expansion may result from the movement of plasma proteins and excess liquid into the airway lumen due to extravasation and elevation of subepithelial hydrostatic pressure. We previously demonstrated that elevation of submucosal hydrostatic pressure increases airway epithelium permeability resulting in ASLV expansion by 500 μL cm−2 h−1. Liquid reabsorption by healthy airway epithelium is regulated by active Na+ transport at a rate of 5 μL cm−2 h−1. Thus, during inflammation the airway epithelium may be submerged by a large volume of luminal liquid. Here, we have investigated the mechanism by which ASLV expansion alters active epithelial Na+ transport, and we have characterized the time course of the change. We used primary cultures of tracheal airway epithelium maintained under air interface (basal ASLV, depth is 7 ± 0.5 μm). To mimic airway flooding, ASLV was expanded to a depth of 5 mm. On switching from basal to expanded ASLV conditions, short-circuit current (Isc, a measure of total transepithelial active ion transport) declined by 90% with a half-time (t1/2) of 1 h. 24 h after the switch, there was no significant change in ATP concentration nor in the number of functional sodium pumps as revealed by [3H]-ouabain binding. However, amiloride-sensitive uptake of 22Na+ was reduced by 70% upon ASLV expansion. This process is reversible since after returning cells back to air interface, Isc recovered with a t1/2 of 5–10 h. These results may have important clinical implications concerning the development of Na+ channels activators and resolution of pulmonary edema. PMID:26333829

  18. [Isoforms of the human histamine H3 receptor: Generation, expression in the central nervous system and functional implications].

    Science.gov (United States)

    García-Gálvez, Ana Maricela; Arias-Montaño, José Antonio

    2016-01-01

    Histamine plays a significant role as a neuromodulator in the human central nervous system. Histamine-releasing neurons are exclusively located in the tuberomammillary nucleus of the hypothalamus, project to all major areas of the brain, and participate in functions such as the regulation of sleep/wakefulness, locomotor activity, feeding and drinking, analgesia, learning, and memory. The functional effects of histamine are exerted through the activation of four G protein-coupled receptors (H1, H2, H3 and H4), and in the central nervous system the first three receptors are widely expressed. The H3 receptor (H3R) is found exclusively in neuronal cells, where it functions as auto- and hetero-receptor. One remarkable characteristic of the H3R is the existence of isoforms, generated by alternative splicing of the messenger RNA. For the human H3R, 20 isoforms have been reported; although a significant number lack those regions required for agonist binding or receptor signaling, at least five isoforms appear functional upon heterologous expression. In this work we review the evidence for the generation of human H3R isoforms, their expression, and the available information regarding the functionality of such receptors.

  19. Postmortem magnetic resonance appearances of congenital high airway obstruction syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Arthurs, Owen J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); UCL Institute of Child Health, London (United Kingdom); Chitty, Lyn S. [UCL Institute of Child Health, Genetics and Genomic Medicine, London (United Kingdom); Great Ormond Street and UCLH NHS Foundation Trusts, London (United Kingdom); Judge-Kronis, Lydia [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Histopathology, London (United Kingdom); Sebire, Neil J. [UCL Institute of Child Health, London (United Kingdom); Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Histopathology, London (United Kingdom)

    2015-04-01

    Congenital high airway obstruction syndrome (CHAOS) is a rare life-threatening condition characterised by complete or near-complete developmental obstruction of the foetal airway. Although antenatal imaging findings have been described, the postmortem MRI findings have not been reported. To present postmortem MRI features of CHAOS. We retrospectively reviewed our hospital pathology and imaging databases for cases of CHAOS over a 2-year period. We identified two cases of CHAOS. In both cases, postmortem plain radiographs demonstrated gross abdominal distension with distortion and splaying of the rib cage. Both foetuses had characteristic postmortem MRI findings including large-volume fluid-filled lungs on T2-weighted imaging, diaphragmatic eversion, fluid-filled airway dilatation below the level of obstruction, centrally positioned and compressed heart, and massive ascites. One foetus had an associated limb abnormality. Postmortem MRI in foetuses suspected of having CHAOS allows confirmation of the diagnosis, determination of the anatomical level of the atresia or stenosis, and identification of associated abnormalities without the need for invasive autopsy. (orig.)

  20. The 'self' in analytical psychology: the function of the 'central archetype' within Fordham's model.

    Science.gov (United States)

    Urban, Elizabeth

    2008-06-01

    This paper concerns the self as Fordham came to conceive it after a conceptual analysis of Jung's use of the term. Fordham identified a contradiction in Jung's usage, and resolved it by reserving 'self' for a definition of the psychosomatic entirety of the individual, and using a separate term for referring to expressions of the self in human experience (e.g. symbols). Fordham tentatively suggested that the latter be termed the 'central archetype', although this was neither developed nor dropped. I explore the value of this term from a developmental perspective and, more specifically in terms of the deintegration of psyche out of an early psychosomatic unity. This draws upon infant research and an observation of a 14-month old boy. Finally, further developments are briefly described and illustrated, whereby pre-symbolic expressions of the central archetype become symbolic and come to reflect what was for Jung, the 'ultimate', 'Formation, Transformation, Eternal Mind's eternal recreation'.

  1. The neurosteroid allopregnanolone modulates specific functions in central and peripheral glial cells

    Directory of Open Access Journals (Sweden)

    Alessandro eFaroni

    2011-12-01

    Full Text Available Since the first observations on the existence of neurosteroids in the 1980’s, our understanding of the importance of these endogenous steroids in the control of the central and peripheral nervous system has increased progressively. Although most of the observations were made in neuronal cells, equally important are the effects that neurosteroids exert on glial cells. Among the different classes of neurosteroids acting on glial cells, the progesterone 5α-3α metabolite, allopregnanolone, displays a particular mechanism of action involving primarily the modulation of classic GABA receptors. In this review, we focus our attention on allopregnanolone because its effects on the physiology of glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues.

  2. ADAMTS expression and function in central nervous system injury and disorders

    Science.gov (United States)

    Gottschall, Paul E.; Howell, Matthew D.

    2016-01-01

    The components of the adult extracellular matrix in the central nervous system form a lattice-like structure that is deposited as perineuronal nets, around axon initial segments and as synapse-associated matrix. An abundant component of this matrix is the lecticans, chondroitin sulfate-bearing proteoglycans that are the major substrate for several members of the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) family. Since lecticans are key regulators of neural plasticity, ADAMTS cleavage of lecticans would likely also contribute to neuroplasticity. Indeed, many studies have examined the neuroplastic contribution of the ADAMTSs to damage and recovery after injury and in central nervous system disease. Much of this data supports a role for the ADAMTSs in recovery and repair following spinal cord injury by stimulating axonal outgrowth after degradation of a glial scar and improving synaptic plasticity following seizure-induced neural damage in the brain. The action of the ADAMTSs in chronic diseases of the central nervous system appears to be more complex and less well-defined. Increasing evidence indicates that lecticans participate in synaptic plasticity in neurodegenerative disease states. It will be interesting to examine how ADAMTS expression and action would affect the progression of these diseases. PMID:25622912

  3. Flow cytometry of sputum: assessing inflammation and immune response elements in the bronchial airways**

    Science.gov (United States)

    Rationale: The evaluation of sputum leukocytes by flow cytometry is an opportunity to assess characteristics of cells residing in the central airways, yet it is hampered by certain inherent properties of sputum including mucus and large amounts of contaminating cells and debris. ...

  4. Obesity, Metabolic Syndrome, and Airway Disease: A Bioenergetic Problem?

    OpenAIRE

    2014-01-01

    Common pathophysiological mechanisms are increasingly being recognized between obesity, metabolic dysfunction, and airway disease. Obesity increases asthma risk or severity, in multiple studies across the globe. Metabolic changes of obesity such as diabetes or insulin resistance are associated with asthma as well as poorer lung function. Insulin resistance has also been found to increase asthma risk independent of body mass. Conversely, asthma has been associated with abnormal glucose and lip...

  5. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

    Full Text Available BACKGROUND: Pulmonary exacerbations (PEx, frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF. Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood. OBJECTIVE: To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx. METHODS: Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d. and late treatment (>7d. for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE; and circulating C-reactive protein (CRP were measured. RESULTS: Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA of Pseudomonas (r = -0.67, p<0.001, decreased FEV(1% predicted (r = 0.49, p = 0.03 and increased CRP (r = -0.58, p = 0.01. In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus. CONCLUSIONS: Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.

  6. ASAP: interactive quantification of 2D airway geometry

    Science.gov (United States)

    D'Souza, Neil D.; Reinhardt, Joseph M.; Hoffman, Eric A.

    1996-04-01

    Evaluation of most normal and patho-pulmonary physiology has relied upon indirect measures of pulmonary function which yield global estimates of underlying structural and functional deficits, which are usually very heterogeneous in nature. Early signs of disease are not recognizable by these techniques, nor are they usually recognizable by the manifestation of physical symptoms. As X-ray CT technology has improved, imaging has held a promise to provide the detailed information here-to-fore missing in standard pulmonary function evaluations. A full solution to the imaging and analysis problem requires true dynamic volumetric approaches to facilitate tracking the lung through space during respiratory maneuvers, and following the radiopacified blood and airflow tracers as they pass through the pulmonary vascular bed or wash in or out of the alveolar air spaces. However, high- resolution, high-speed, stacked single-slice approaches for lung imaging have brought the state-of-the-art to a point where quantitative airway evaluation can play an important role in the study of lung disease and normal lung physiology, if one limits the evaluation to those airway segmented sliced in true cross-sections, or to the evaluation of those airway segments for which a true cross-sectional image can be reformatted from the original stacked sections. This paper presents a software system, called ASAP (for Airway Segmentation and Analysis Program), which provides a rapid, minimally-interactive method for objective identification of airway borders and the reporting of associated geometric measures of diameters and wall thicknesses. We demonstrate that this system yields highly reproducible results both within and between observers, and quantitative measures are accurate to within the resolution of the scanner when phantoms of known geometry are evaluated. Results included here demonstrate that the well-accepted half-max criteria for border definition is a rough approximation, which when

  7. Numerical simulation of soft palate movement and airflow in human upper airway by fluid-structure interaction method

    Science.gov (United States)

    Sun, Xiuzhen; Yu, Chi; Wang, Yuefang; Liu, Yingxi

    2007-08-01

    In this paper, the authors present airflow field characteristics of human upper airway and soft palate movement attitude during breathing. On the basis of the data taken from the spiral computerized tomography images of a healthy person and a patient with Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS), three-dimensional models of upper airway cavity and soft palate are reconstructed by the method of surface rendering. Numerical simulation is performed for airflow in the upper airway and displacement of soft palate by fluid-structure interaction analysis. The reconstructed three-dimensional models precisely preserve the original configuration of upper airways and soft palate. The results of the pressure and velocity distributions in the airflow field are quantitatively determined, and the displacement of soft palate is presented. Pressure gradients of airway are lower for the healthy person and the airflow distribution is quite uniform in the case of free breathing. However, the OSAHS patient remarkably escalates both the pressure and velocity in the upper airway, and causes higher displacement of the soft palate. The present study is useful in revealing pathogenesis and quantitative mutual relationship between configuration and function of the upper airway as well as in diagnosing diseases related to anatomical structure and function of the upper airway.

  8. Numerical simulation of soft palate movement and airflow in human upper airway by fluid-structure interaction method

    Institute of Scientific and Technical Information of China (English)

    Xiuzhen Sun; Chi Yu; Yuefang Wang; Yingxi Liu

    2007-01-01

    In this paper, the authors present airflow field characteristics of human upper airway and soft palate move-ment attitude during breathing. On the basis of the data taken from the spiral computerized tomography images of a healthy person and a patient with Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS), three-dimensional models of upper air-way cavity and soft palate are reconstructed by the method of surface rendering. Numerical simulation is performed for airflow in the upper airway and displacement of soft palate by fluid-structure interaction analysis. The reconstructed three-dimensional models precisely preserve the original config-uration of upper airways and soft palate. The results of the pressure and velocity distributions in the airflow field are quantitatively determined, and the displacement of soft palate is presented. Pressure gradients of airway are lower for the healthy person and the airflow distribution is quite uniform in the case of free breathing. However, the OSAHS patient remarkably escalates both the pressure and velocity in the upper airway, and causes higher displacement of the soft palate. The present study is useful in revealing pathogenesis and quantitative mutual relationship between configuration and function of the upper airway as well as in diagnosing diseases related to anatomical structure and function of the upper airway.

  9. Extraction of Airways from CT (EXACT’09)

    DEFF Research Database (Denmark)

    Lo, Pechin; Ginneken, Bram van; Reinhardt, Joseph M.;

    2012-01-01

    This paper describes a framework for establishing a reference airway tree segmentation, which was used to quantitatively evaluate 15 different airway tree extraction algorithms in a standardized manner. Because of the sheer difficulty involved in manually constructing a complete reference standar...

  10. c-function and central charge of the sine-Gordon model from the non-perturbative renormalization group flow

    Directory of Open Access Journals (Sweden)

    V. Bacsó

    2015-12-01

    Full Text Available In this paper we study the c-function of the sine-Gordon model taking explicitly into account the periodicity of the interaction potential. The integration of the c-function along trajectories of the non-perturbative renormalization group flow gives access to the central charges of the model in the fixed points. The results at vanishing frequency β2, where the periodicity does not play a role, are retrieved and the independence on the cutoff regulator for small frequencies is discussed. Our findings show that the central charge obtained integrating the trajectories starting from the repulsive low-frequencies fixed points (β2<8π to the infra-red limit is in good quantitative agreement with the expected Δc=1 result. The behavior of the c-function in the other parts of the flow diagram is also discussed. Finally, we point out that including also higher harmonics in the renormalization group treatment at the level of local potential approximation is not sufficient to give reasonable results, even if the periodicity is taken into account. Rather, incorporating the wave-function renormalization (i.e. going beyond local potential approximation is crucial to get sensible results even when a single frequency is used.

  11. Cadmium regulates the expression of the CFTR chloride channel in human airway epithelial cells.

    Science.gov (United States)

    Rennolds, Jessica; Butler, Susie; Maloney, Kevin; Boyaka, Prosper N; Davis, Ian C; Knoell, Daren L; Parinandi, Narasimham L; Cormet-Boyaka, Estelle

    2010-07-01

    Cadmium is a toxic heavy metal ranked seventh on the Priority List of Hazardous Substances. As a byproduct of smelters, cadmium is a prevalent environmental contaminant. It is also a major component of cigarette smoke, and its inhalation is associated with decreased pulmonary function, lung cancer, and chronic obstructive pulmonary disease. Ion channels, including the cystic fibrosis transmembrane conductance regulator (CFTR), play a central role in maintaining fluid homeostasis and lung functions. CFTR is mostly expressed in epithelial cells, and little is known about the effect of cadmium exposure on lung epithelial cell function. We show that exposure to cadmium decreases the expression of the CFTR protein and subsequent chloride transport in human airway epithelial cells in vitro. Impairment of CFTR protein expression was also observed in vivo in the lung of mice after intranasal instillation of cadmium. We established that the inhibitory effect of cadmium was not a nonspecific effect of heavy metals, as nickel had no effect on CFTR protein levels. Finally, we show that selected antioxidants, including alpha-tocopherol (vitamin E), but not N-acetylcysteine, can prevent the cadmium-induced suppression of CFTR. In summary, we have identified cadmium as a regulator of the CFTR chloride channel present in lung epithelial cells. Future strategies to prevent the deleterious effect of cadmium on epithelial cells and lung functions may benefit from the finding that alpha-tocopherol protects CFTR expression and function.

  12. Extraction of airways from CT (EXACT’09)

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Ginneken, Bram van; Reinhardt, Joseph M.

    2012-01-01

    This paper describes a framework for establishing a reference airway tree segmentation, which was used to quantitatively evaluate 15 different airway tree extraction algorithms in a standardized manner. Because of the sheer difficulty involved in manually constructing a complete reference standard...... or not it is a correctly segmented part of the airway tree. Finally, the reference airway trees are constructed by taking the union of all correctly extracted branch segments. Fifteen airway tree extraction algorithms from different research groups are evaluated on a diverse set of 20 chest computed tomography (CT) scans...... from the evaluation showed that no single algorithm could extract more than an average of 74% of the total length of all branches in the reference standard, indicating substantial differences between the algorithms. A fusion scheme that obtained superior results is presented, demonstrating...

  13. Screening of central functions of amino acids and their metabolites for sedative and hypnotic effects using chick models.

    Science.gov (United States)

    Furuse, Mitsuhiro

    2015-09-01

    The chick has a practical advantage in the screening process in that chicks require only small quantities of drugs. The chick separation stress paradigm has traditionally been recognized as a valid form of anxiolytic screening. Further, chick behavior involving standing motionless with eyes closed or sitting motionless with head drooped is nearly always associated with electrophysiological sleep. When centrally administered, some DNA-encoded L-α-amino acids, as well as some DNA-non-encoded amino acids, such as metabolites of L-α-amino acids, D-amino acid and β-amino acid, have shown sedative and/or hypnotic effects in chicks. The effects of some of these amino acids have subsequently been confirmed in humans. In conclusion, the chick model is convenient and useful for screening central functions of amino acids and their metabolites for hypnosis and sedation.

  14. 安氏 II 类下颌后缩儿童应用 Twin-block 矫治器功能矫治前后上气道变化的锥形束 CT 研究%A CBCT study on the upper airway of the children with Class Ⅱ mandibular retrusion before and after functional treatment by Twin-block appliance

    Institute of Scientific and Technical Information of China (English)

    史建陆; 董丽玲; 李芸; 贺红

    2015-01-01

    目的:探讨安氏Ⅱ类下颌后缩儿童患者功能矫治前后上气道的三维变化。方法:用 Twin-block 矫治器治疗下颌后缩儿童患者,拍摄其矫治前后的锥形束 CT,应用 Dolphin 11.5软件进行三维测量分析,采用配对 t 检验对安氏Ⅱ类下颌后缩患者功能矫治前后上气道的变化进行比较。结果:患者上气道的总体积、腭咽、舌咽、喉咽、口咽体积,软腭尖平面(SP)、会厌顶平面(TE)上气道的截面积,口咽段最小截面积,SP 矢状径、横径,TE 横径均显著增大(P <0.05);气道形态在 SP 趋于圆形,而在 TE 趋于扁平(P <0.05)。结论:Twin-block 功能矫治能使下颌后缩儿童上气道增大,改善呼吸功能。%Objective:To study the changes of upper airway dimension and morphology in Class Ⅱ mandibular retrusion children af-ter functional treatment by Twin-block appliance.Methods:The Cone-Beam CT(CBCT)data of upper airway of the subjects were measured with Dolphin 11.5 software before and after fuctional treatment by Twin-block appliance.The comparison of upper airway di-mension and morphology between pre-treatment and post-treatment was performed by paired t-text.Results:After functional treatment the volume of total upper airway,velopharyngeal airway,glossopharyngeal airway,laryngopharyngeal airway,oropharyngeal airway,the sectional area of the inferior of the soft palate(SP),tip of the epiglotti(TE),the sagittal diameter of SP,the lateral diameter of SP and TE increased(P <0.05)in the children;the airway's shape of SP was attended to be rounder and TE to be more flat.Conclusion:Functional treatment is effective in the treatment of skeletal Class Ⅱ mandibular retrusion of children by increase of the upper airway and improvement of respiration.

  15. Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway

    Science.gov (United States)

    Huang, Miao-Tzu; Chen, Yi-Lien; Lien, Chia-I; Liu, Wei-Liang; Hsu, Li-Chung; Yagita, Hideo; Chiang, Bor-Luen

    2017-01-01

    Notch is a pleiotropic signaling family that has been implicated in pathogenesis of allergic airway diseases; however, the distinct function of individual Notch ligands remains elusive. We investigated whether Notch ligands, Jagged1 and DLL4, exert differential effects in OVA-induced allergic asthma. We found that whilst Jagged1 inhibition mitigated Th2-dominated airway inflammation, blockage of DLL4 aggravated the Th2-mediated asthma phenotypes. Additionally, Jagged1 signaling blockage enhanced IL-17 production and neutrophilic airway infiltration. In vitro, exogenous Jagged1 induced Th2-skewed responses, whereas augmented DLL4 signaling displayed a dual role by promoting expansion of both Tregs and Th17. In vivo, DLL4 blockage impaired Treg differentiation which plausibly resulted in exaggerated asthma phenotypes. On the contrary, administration of DLL4-expressing antigen-presenting cells promoted endogenous Treg expansion and ameliorated the allergic responses. Therefore, whilst Jagged1 induces Th2-skewed inflammation, DLL4 elicits an essential self-regulatory mechanism via Treg-mediated pathway that counterbalances Jagged1-induced Th2 responses and facilitates resolution of the airway inflammation to restore homeostasis. These findings uncover a disparate function of Jagged1 and DLL4 in allergic airway diseases, hinting feasibility of Notch ligand-specific targeting in therapy of allergic airway diseases. PMID:28262821

  16. Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Borst Mathias M

    2009-12-01

    Full Text Available Abstract Background In idiopathic pulmonary arterial hypertension (IPAH, peripheral airway obstruction is frequent. This is partially attributed to the mediator dysbalance, particularly an excess of endothelin-1 (ET-1, to increased pulmonary vascular and airway tonus and to local inflammation. Bosentan (ET-1 receptor antagonist improves pulmonary hemodynamics, exercise limitation, and disease severity in IPAH. We hypothesized that bosentan might affect airway obstruction. Methods In 32 IPAH-patients (19 female, WHO functional class II (n = 10, III (n = 22; (data presented as mean ± standard deviation pulmonary vascular resistance (11 ± 5 Wood units, lung function, 6 minute walk test (6-MWT; 364 ± 363.7 (range 179.0-627.0 m, systolic pulmonary artery pressure, sPAP, 79 ± 19 mmHg, and NT-proBNP serum levels (1427 ± 2162.7 (range 59.3-10342.0 ng/L were measured at baseline, after 3 and 12 months of oral bosentan (125 mg twice per day. Results and Discussion At baseline, maximal expiratory flow at 50 and 25% vital capacity were reduced to 65 ± 25 and 45 ± 24% predicted. Total lung capacity was 95.6 ± 12.5% predicted and residual volume was 109 ± 21.4% predicted. During 3 and 12 months of treatment, 6-MWT increased by 32 ± 19 and 53 ± 69 m, respectively; p Conclusion This study gives first evidence in IPAH, that during long-term bosentan, improvement of hemodynamics, functional parameters or serum biomarker occur independently from persisting peripheral airway obstruction.

  17. The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Bonini, Matteo; Usmani, Omar S

    2015-12-01

    Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), represent a major social and economic burden for worldwide health systems. During recent years, increasing attention has been directed to the role of small airways in respiratory diseases, and their exact contribution to the pathophysiology of asthma and COPD continues to be clarified. Indeed, it has been suggested that small airways play a distinct role in specific disease phenotypes. Besides providing information on small airways structure and diagnostic procedures, this review therefore aims to present updated and evidence-based findings on the role of small airways in the pathophysiology of asthma and COPD. Most of the available information derives from either pathological studies or review articles and there are few data on the natural history of small airways disease in the onset or progression of asthma and COPD. Comparisons between studies on the role of small airways are hard to draw because both asthma and COPD are highly heterogeneous conditions. Most studies have been performed in small population samples, and different techniques to characterize aspects of small airways function have been employed in order to assess inflammation and remodelling. Most methods of assessing small airways dysfunction have been largely confined to research purposes, but some data are encouraging, supporting the utilization of certain techniques into daily clinical practice, particularly for early-stage diseases, when subjects are often asymptomatic and routine pulmonary function tests may be within normal ranges. In this context further clinical trials and real-life feedback on large populations are desirable.

  18. Functional Analysis of Actin-Binding Proteins in the Central Nervous System of Drosophila.

    Science.gov (United States)

    He, Qi; Roblodowski, Christopher

    2016-01-01

    Using Drosophila actin-binding protein Dunc-115 as model system, this chapter describes a MARCM (mosaic analysis with a repressible cell marker)-based method for analyzing cytoskeletal components for their functions in the nervous system. Following a concise description about the principle, a step-by-step protocol is provided for generating the needed stocks and for histological analysis. Additional details and explanations have been given in the accompanying notes. Together, this should form a practical and sufficient recipe for performing at the single-cell-level loss-of-function and gain-of-function analyses of proteins associated with the cytoskeleton.

  19. Working activity hygiene, central nervous system and attention function parameters of the working females at knitting enterprises of Uzbekistan

    Directory of Open Access Journals (Sweden)

    Aziz Iskandarov

    2013-04-01

    Full Text Available Last years in Uzbekistan the knitted manufactures have developed intensively, supplied with the new equipment and modern technologies which result in change of working conditions at the knitted-goods enterprises, in increase of intensity, strained nervous-emotional state and intellectuality of working processes. The purpose was to reveal influence of working conditions of the working women of knitted manufactures on dynamics of working activity, on the central nervous system and functions of attention. The healthy working women of the Tashkent knitted manufactures making a knitted cloth and wears (knitters, seamstresses, ironers at the age from 20 till 40 years with the operational experience from 2 till 20 years were enrolled in this study. It was established that of all unfavourable factors that effect on the reduction of the working activity the air dust contamination accounts for 13.6%, noise 13.6% and light exposure of workplace 32.4%. For decrease of a functional strain of the central nervous system and function of attention of the working women it is necessary to introduce the rational mode of work and rest as well as measures for improvement of working conditions.

  20. Morphologic aspects of airways of patients with pulmonary emphysema followed by bronchial asthma-like attack.

    Science.gov (United States)

    Haraguchi, M; Shimura, S; Shirato, K

    1996-02-01

    Morphometric analysis of airways was performed in autopsied lungs from four patients with pulmonary emphysema (PE) followed by bronchial-asthma (BA)-like attacks (Group PE+BA) (four males, 72 +/- 9 yr). The results were compared with those from five pulmonary emphysema patients (Group PE) (five males, age 71 +/- 4 hr), three patients with bronchial asthma (Group BA) (one female and two males, age 65 +/- 7 yr), and four control subjects with no pulmonary diseases (Group Cont) (one female, three males, age 64 +/- 4 yr). The proportion of gland area to bronchial wall (gland%), ratio of goblet-cell occupancy to the total epithelial layer (goblet%), thickness of the basement membrane, amount of intraluminal mucus (mucus occupying ratio; MOR%), and number of various cell types per square millimeter in airway walls in a section 4 microns thick were measured in central (3 to 8 mm diameter) and peripheral airways (2 mm or less diameter). Gland% for the PE+BA group was significantly greater than that for the Cont group, whereas it did not differ significantly from that of the PE or BA groups. Goblet% and thickness of the basement membrane in central and/or peripheral airways in Group PE+BA were significantly greater than those in Group Cont, whereas those in Group PE were similar to those in Group Cont. Although not statistically significant, MOR% in central and peripheral airways from Group PE+BA showed a similar value to that in Group BA, whereas MOR% in Group PE was the same as that in Group Cont. The eosinophil number in peripheral airways walls in Group PE+BA showed a similar value to that in Group BA, which was significantly greater than in Group Cont. Other cells (macrophages, lymphocytes, and neutrophils) showed similar values among Groups PE+BA, PE, and BA. The number of eosinophils in central and/or peripheral airways correlated significantly with both goblet% and BMT, whereas other cells did not. These findings indicate that the airways of Group PE+BA are

  1. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans

    NARCIS (Netherlands)

    Smeekens, Sanne P.; Ng, Aylwin; Kumar, Vinod; Johnson, Melissa D.; Plantinga, Theo S.; van Diemen, Cleo; Arts, Peer; Verwiel, Eugene T. P.; Gresnigt, Mark S.; Fransen, Karin; van Sommeren, Suzanne; Oosting, Marije; Cheng, Shih-Chin; Joosten, Leo A. B.; Hoischen, Alexander; Kullberg, Bart-Jan; Scott, William K.; Perfect, John R.; van der Meer, Jos W. M.; Wijmenga, Cisca; Netea, Mihai G.; Xavier, Ramnik J.

    2013-01-01

    Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. Here by integrating transcriptional analysis and functional genomics, we identified Candida-specific host defence mechanisms in humans. Candid

  2. The central role of trunk control in the gross motor function of children with cerebral palsy

    DEFF Research Database (Denmark)

    Curtis, Derek John; Butler, Penny; Saavedra, Sandy;

    2015-01-01

    Aim Improvement of gross motor function and mobility are primary goals of physical therapy in children with cerebral palsy (CP). The purpose of this study was to investigate the relationship between segmental control of the trunk and the corresponding gross motor function in children with CP....... Method This retrospective cross-sectional study was based on 92 consecutive referrals of children with CP in Gross Motor Function Classification System (GMFCS) levels I to V, 39 females, 53 males (median age 4y [range 1–14y]), and 77, 12, and 3 with spastic, dyskinetic, and ataxic CP respectively....... The participants were tested using the Gross Motor Function Measure (GMFM), the Pediatric Evaluation of Disability Inventory (PEDI), and the Segmental Assessment of Trunk Control (SATCo). Results Linear regression analysis showed a positive relationship between the segmental level of trunk control and age...

  3. A reconstruction of Atlantic Central African biomes and forest succession stages derived from modern pollen data and plant functional types

    Directory of Open Access Journals (Sweden)

    J. Lebamba

    2009-01-01

    Full Text Available New detailed vegetation reconstructions are proposed in Atlantic Central Africa from a modern pollen data set derived from 199 sites (Cameroon, Gabon and Congo including 131 new sites. In this study, the concept of plant functional classification is improved with new and more detailed plant functional types (PFTs and new aggregations of pollen taxa. Using the biomisation method, we reconstructed (1 modern potential biomes and (2 potential succession stages of forest regeneration, a new approach in Atlantic Central African vegetation dynamics and ecosystem functioning reconstruction. When compared to local vegetation, potential biomes are correctly reconstructed (97.5% of the sites and tropical evergreen to semi-evergreen forest (TRFO biome is well identified from semi-deciduous forest (TSFO biome. When the potential biomes are superimposed on the White's vegetation map, only 76.4% of the sites are correctly reconstructed. But using botanical data, correspondence and cluster analyses, the 43 sites from Congo (Mayombe evidence more affinities with those of central Gabon and so they can also be considered as correctly reconstructed as TRFO biome and White's map must be revised. In terms of potential succession stages of forest regeneration, the mature forest (TMFO is well differentiated from the secondary forest (TSFE, but inside this latter group, the young and the pioneer stages are not clearly identified due probably to their low sampling representation. Moreover, linked to their progressive and mosaic character, the boundaries between two forest biomes or two forest stages are not clearly detected and need also a more intensive sampling in such transitions.

  4. [14C]deoxyglucose labelling of functional activity in the cephalopod central nervous system.

    Science.gov (United States)

    Novicki, A; Messenger, J B; Budelmann, B U; Terrell, M L; Kadekaro, M

    1992-07-22

    For the first time, the [14C]deoxyglucose radioautographic technique has been successfully used to map physiological activity in cephalopod brains. In unilaterally blinded octopus and cuttlefish, the optic lobe of the deprived side showed a decreased uptake of the labelled tracer. This suggests that the uptake is related to functional activity. The potential of the [14C]deoxyglucose technique as a powerful tool in studying the functional organization of cephalopod brains is discussed.

  5. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Huang, Yvonne J; Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A; Lynch, Susan V

    2014-08-01

    Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥ 2-fold, P microbiome could be useful indicators of exacerbation development or outcome.

  6. Membrane Currents in Airway Smooth Muscle: Mechanisms and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Luke J Janssen

    1997-01-01

    Full Text Available Electrophysiological and pharmacological techniques were used to characterize the membrane conductance changes underlying spasmogen-evoked depolarization in airway smooth muscle (ASM. Changes included a transient activation of chloride ion channels and prolonged suppression of potassium ion channels; both changes are triggered by release of internally sequestered calcium ion and in turn cause opening of voltage-dependent calcium channels. The resultant influx of calcium ions contributes to contraction as well as to refilling of the internal calcium ion pool. Bronchodilators, on the other hand, act in part through activation of potassium channels, with consequent closure of calcium channels. The tools used to study ion channels in ASM are described, and the investigations of the roles of ion channels in ASM physiology (autacoid-evoked depolarization and hyperpolarization and pathophysiology (airway hyperresponsiveness are summarized. Finally, how the relationship between ion channels and ASM function/dysfunction may relate to the treatment of asthma and related breathing disorders is discussed.

  7. Plethysmographic measurements of specific airway resistance in young children

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Nielsen, Kim G

    2005-01-01

    children. This article reviews the method, and proposes a protocol and criteria for quality assurance for assessment of sRaw in preschool children from 2 years of age. sRaw measurements offers a method for clinical monitoring and research during this critical period of growth and development early in life.......Validated methods for lung function measurements in young children are lacking. Plethysmographic measurement of specific airway resistance (sRaw) provides such a method applicable from 2 years of age. sRaw gauges airway resistance from the measurements of the pressure changes driving the airflow...... also been documented by this technique, and sRaw has recently been used in longitudinal studies of young children with chronic pulmonary diseases. Future developments should provide improved algorithms for thermal correction of the respired volumes and adapt the equipment to the special needs of young...

  8. European symposium on precision medicine in allergy and airways diseases

    DEFF Research Database (Denmark)

    Muraro, A; Fokkens, W J; Pietikainen, S

    2015-01-01

    On 14 October 2015, the European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS) and the European Medical Association (EMA) organized a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP...... suffering from allergies and asthma, more than half of these patients are deprived from adequate diagnosis and treatment. Precision Medicine represents a novel approach in medicine, embracing 4 key features: personalized care based on molecular, immunologic and functional endotyping of the disease......, with participation of the patient in the decision making process of therapeutic actions, and taking into account predictive and preventive aspects of the treatment. Implementation of Precision Medicine into clinical practice may help to achieve the arrest of the Epidemic of Allergies and Chronic Airways Diseases...

  9. European symposium on precision medicine in allergy and airways diseases

    DEFF Research Database (Denmark)

    Muraro, A; Fokkens, W J; Pietikainen, S

    2015-01-01

    On 14 October 2015, the European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS) and the European Medical Association (EMA) organized a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP...... Effectiveness Group (REG). MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, underlined the importance of the need for a better diagnostic and therapeutic approach for patients with Allergies and Chronic Airways Diseases, and encouraged a joint initiative to control...... suffering from allergies and asthma, more than half of these patients are deprived from adequate diagnosis and treatment. Precision Medicine represents a novel approach in medicine, embracing 4 key features: personalized care based on molecular, immunologic and functional endotyping of the disease...

  10. Effect of cadmium or magnesium on calcium-dependent central function that reduces blood pressure

    Energy Technology Data Exchange (ETDEWEB)

    Sutoo, D.; Akiyama, K. [Univ. of Tsukuba (Japan). Inst. of Medical Sci.

    2000-03-01

    The effect of intracerebroventricular (i.c.v.) administration of cadmium or magnesium on central calcium-dependent blood pressure regulation was investigated. The systolic blood pressure of spontaneously hypertensive rats (SHR; male, 13 weeks of age) decreased following i.c.v. administration of cadmium chloride (20 nmol/rat), and increased following i.c.v. administration of magnesium chloride (20, 600, and 1200 nmol/rat). The hypotensive effect of cadmium was suppressed by i.c.v. administration of W-7 (a calmodulin antagonist, 30 {mu}g/rat). Taking into consideration these results with our previous reports, it is suggested that cadmium binds to the calcium-binding sites of calmodulin and activates calcium/calmodulin-dependent enzymes in a disorderly manner, whereas magnesium does not. Therefore, cadmium increases dopamine synthesis in the brain via a calmodulin-dependent system, and the resultant increase in dopamine levels inhibits sympathetic nerve activity and reduces blood pressure in SHR. (orig.)

  11. Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

    Institute of Scientific and Technical Information of China (English)

    Xian-hui Dong; Cong Liu; Jiang-tao Bai; Wei-na Kong; Xiao-ping He; Peng Yan; Tie-mei Shao; Wen-guo Yu; Xi-qing Chai; Yan-hua Wu

    2015-01-01

    Abnormally increased levels of iron in the brain trigger cascade ampliifcation in Alzheimer’s dis-ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer’s disease patients. An APPswe/PS1ΔE9 double transgenic mouse model of Alzheimer’s disease was used. The intragas-tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer’s disease. These com-pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer’s disease.

  12. Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

    Directory of Open Access Journals (Sweden)

    Xian-hui Dong

    2015-01-01

    Full Text Available Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer′s disease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer′s disease patients. An APP swe/PS1ΔE9 double transgenic mouse model of Alzheimer′s disease was used. The intragastric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer′s disease. These compounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer′s disease.

  13. Sensitivity and Reliability in Incomplete Networks: Centrality Metrics to Community Scoring Functions

    CERN Document Server

    Sarkar, Soumya; Kumar, Suhansanu; Mukherjee, Animesh

    2016-01-01

    Network analysis is an important tool in understanding the behavior of complex systems of interacting entities. However, due to the limitations of data gathering technologies, some interactions might be missing from the network model. This is a ubiquitous problem in all domains that use network analysis, from social networks to hyper-linked web networks to biological networks. Consequently, an important question in analyzing networks is to understand how increasing the noise level (i.e. percentage of missing edges) affects different network parameters. In this paper we evaluate the effect of noise on community scoring and centrality-based parameters with respect to two different aspects of network analysis: (i) sensitivity, that is how the parameter value changes as edges are removed and (ii) reliability in the context of message spreading, that is how the time taken to broadcast a message changes as edges are removed. Our experiments on synthetic and real-world networks and three different noise models demon...

  14. Quantitative analysis of dynamic airway changes after methacholine and salbutamol inhalation on xenon-enhanced chest CT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Joon; Goo, Jin Mo; Kim, Jong Hyo; Park, Eun-Ah [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Lee, Chang Hyun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Jung, Jae-Woo; Park, Heung-Woo [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of); Cho, Sang-Heon [Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of)

    2012-11-15

    To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics. Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis. TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P < 0.05). Of the airway parameters, the airway inner area (IA) significantly increased after salbutamol inhalation in all airways (P < 0.01) in asthmatics. Airway IA, wall thickness and wall area percentage did not significantly decrease after methacholine inhalation (P > 0.05). IA of the large airways was well correlated with basal TXVI, FEV{sub 1} and FVC (P < 0.05). Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT. (orig.)

  15. Electrical circuit models of the human respiratory system reflect small airway impairment measured by impulse oscillation (IOS).

    Science.gov (United States)

    Goldman, Michael D; Nazeran, Homer; Ramos, Carlos; Toon, Emily; Oates, Katrina; Bilton, Diana; Meraz, Erika; Hafezi, Nazila; Diong, Bill

    2010-01-01

    The use of the forced oscillatory input impedance parameter, frequency-dependence of Resistance (fdR), to assess small airway impairment (SAI) has not been widely accepted due to concern about the effects of "upper airway shunt" on oscillometric resistance and low frequency reactance. On the other hand, recent medical studies suggest that low frequency reactance is a very sensitive index of treatment intervention directed at small airways. The present study was undertaken to analyze and compare Impulse Oscillometry (IOS) resistance and reactance data with model-derived indices of small airway function from two models of the respiratory impedance, one with, and the other without an element for upper airway shunt capacitance. Fifty six patients with stable chronic obstructive lung disease of varying severity due to Cystic Fibrosis (CF) and 21 patients with asthma were evaluated by IOS testing. IOS data were input into the augmented RIC (aRIC) model with an upper airway shunt capacitance, and the extended RIC (eRIC) model, without a shunt capacitance element. Model-derived indices were compared between the two models for CF patients separately from asthma patients. We conclude that IOS indices of SAI are modeled equally well with or without upper airway shunt capacitance, and do not seem to be dependent on upper airway shunt capacitance.

  16. Spirometric abnormalities associated with chronic bronchitis, asthma, and airway hyperresponsiveness among boilermaker construction workers

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, R.; Eisen, E,A,; Pothier, L,; Lewis, D,; Bledsoe, T,; Christiani, D.C. [Harvard University, Boston, MA (United States). School of Public Health

    2002-06-01

    In a 2-year longitudinal study of boilermaker construction workers, authors found a significant association between working at oil-fired, coal-fired, and gas-fired industries during the past year and reduced lung function. In the present study, authors investigated whether chronic bronchitis, asthma, or baseline methacholine airway responsiveness can explain the heterogeneity in lung function response to boilermaker work. Exposure was assessed with a work history questionnaire. Spirometry was performed annually to assess lung function. A generalized estimating equation approach was used to account for the repeated-measures design. One hundred eighteen boilermakers participated in the study. Self-reported history of chronic bronchitis and asthma were associated with a larger FEV1 reduction in response to workplace exposure at coal-fired and gas-fired industries. Although a high prevalence (39%) of airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEVI of {lt} 8 mg/mL) among boilermakers was found, there was no consistent pattern of effect modification by airway responsiveness. Conclusions: Although chronic bronchitis and asthma were associated with a greater loss in lung function in response to hours worked as a boilermaker, and therefore they acted as effect modifiers of the exposure-lung function relationship, airway hyperresponsiveness did not. However, the high prevalence of airway hyperresponsiveness found in the cohort may be a primary consequence of long-term workplace exposure among boilermakers.

  17. In vivo role of platelet-derived growth factor-BB in airway smooth muscle proliferation in mouse lung.

    Science.gov (United States)

    Hirota, Jeremy A; Ask, Kjetil; Farkas, Laszlo; Smith, Jane Ann; Ellis, Russ; Rodriguez-Lecompte, Juan Carlos; Kolb, Martin; Inman, Mark D

    2011-09-01

    Airway smooth muscle (ASM) hyperplasia in asthma likely contributes considerably to functional changes. Investigating the mechanisms behind proliferation of these cells may lead to therapeutic benefit. Platelet-derived growth factor (PDGF)-BB is a well known ASM mitogen in vitro but has yet to be directly explored using in vivo mouse models in the context of ASM proliferation and airway responsiveness. To determine the in vivo influence of PDGF-BB on gene transcripts encoding contractile proteins, ASM proliferation, and airway physiology, we used an adenovirus overexpression system and a model of chronic allergen exposure. We used adenovirus technology to selectively overexpress PDGF-BB in the airway epithelium of mice. Outcome measurements, including airway physiology, real time RT-PCR measurements, proliferating cell nuclear antigen staining, and airway smooth muscle quantification, were performed 7 days after exposure. The same outcome measurements were performed 24 hours and 4 weeks after a chronic allergen exposure model. PDGF-BB overexpression resulted in airway hyperresponsiveness, decreased lung compliance, increased airway smooth muscle cell numbers, positive proliferating cell nuclear antigen-stained airway smooth muscle cells, and a reduction in genes encoding contractile proteins. Chronic allergen exposure resulted in elevations in lung lavage PDGF-BB, which were observed in conjunction with changes in gene transcript expression encoding contractile proteins and ASM proliferation. We demonstrate for the first time in vivo that PDGF-BB induces ASM hyperplasia and changes in lung mechanics in mice and that, during periods of allergen exposure changes in lung, PDGF-BB are associated with changes in airway structure and function.

  18. Effector and Central Memory Poly-functional CD4+ and CD8+ T cells are Boosted upon ZOSTAVAX® Vaccination

    Directory of Open Access Journals (Sweden)

    Kalpit A Vora

    2015-10-01

    Full Text Available ZOSTAVAX® is a live attenuated varicella-zoster virus (VZV vaccine that is licensed for the protection of individuals ≥ 50 years against shingles, and its most common complication, post-herpetic neuralgia. While IFN responses increase upon vaccination, the quality of the T cell response has not been elucidated. By using polychromatic flow cytometry, we characterized the breadth, magnitude, and quality of ex vivo CD4+ and CD8+ T cell responses induced 3 – 4 weeks after ZOSTAVAX vaccination of healthy adults. We show, for the first time that the highest frequencies of VZV-specific CD4+ T cells were poly-functional CD154+IFNγ+IL-2+TNFα+ cells, which were boosted upon vaccination. The CD4+ T cells were broadly reactive to several VZV proteins, with IE63 ranking the highest amongst them in the fold-rise of poly-functional cells, followed by IE62, gB, ORF9, and gE. We identified a novel poly-functional ORF9-specific CD8+ T cell population in 62% of the subjects, and these were boosted upon vaccination. Poly-functional CD4+ and CD8+ T cells produced significantly higher levels of IFNγ, IL-2, and TNFα compared to mono-functional cells. After vaccination, a boost in the expression of IFN by poly-functional IE63-and ORF9-specific CD4+ T cells, and IFNγ, IL-2, and TNFα by ORF9-specific poly-functional CD8+ T cells was observed. Responding poly-functional T cells exhibited both effector (CCR7−CD45RA−CD45RO+, and central (CCR7+CD45RA−CD45RO+ memory phenotypes, which expressed comparable levels of cytokines. Altogether, our studies demonstrate that a boost in memory poly-functional CD4+ T cells, and ORF9-specific CD8+ T cells may contribute towards ZOSTAVAX efficacy.

  19. The genus Prevotella in cystic fibrosis airways.

    Science.gov (United States)

    Field, Tyler R; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2010-08-01

    Airway disease resulting from chronic bacterial colonization and consequential inflammation is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Although traditionally considered to be due to only a few pathogens, recent re-examination of CF airway microbiology has revealed that polymicrobial communities that include many obligate anaerobes colonize lower airways. The purpose of this study was to examine Prevotella species in CF airways by quantitative culture and phenotypic characterization. Expectorated sputum was transferred to an anaerobic environment immediately following collection and examined by quantitative microbiology using a variety of culture media. Isolates were identified as facultative or obligate anaerobes and the later group was identified by 16S rRNA sequencing. Prevotella spp. represented the majority of isolates. Twelve different species of Prevotella were recovered from 16 patients with three species representing 65% of isolates. Multiple Prevotella species were often isolated from the same sputum sample. These isolates were biochemically characterized using Rapid ID 32A kits (BioMérieux), and for their ability to produce autoinducer-2 and beta-lactamases. Considerable phenotypic variability between isolates of the same species was observed. The quantity and composition of Prevotella species within a patients' airway microbiome varied over time. Our results suggest that the diversity and dynamics of Prevotella in CF airways may contribute to airway disease.

  20. Upper airway collapsibility in anesthetized children.

    Science.gov (United States)

    Litman, Ronald S; McDonough, Joseph M; Marcus, Carole L; Schwartz, Alan R; Ward, Denham S

    2006-03-01

    We sought to establish the feasibility of measuring upper airway narrowing in spontaneously breathing, anesthetized children using dynamic application of negative airway pressure. A secondary aim was to compare differences in upper airway collapsibility after the administration of sevoflurane or halothane. Subjects were randomized to either drug for inhaled anesthetic induction. Each was adjusted to their 1 MAC value (0.9% for halothane and 2.5% for sevoflurane) and a blinded anesthesia provider held the facemask without performing manual airway opening maneuvers but with inclusion of an oral airway device. Inspiratory flows were measured during partial upper airway obstruction created by an adjustable negative pressure-generating vacuum motor inserted into the anesthesia circuit. Critical closing pressure of the pharynx (Pcrit) was obtained by plotting the peak inspiratory flow of the obstructed breaths against the corresponding negative pressure in the facemask and extrapolating to zero airflow using linear correlation. Fourteen children were enrolled, seven in each anesthetic group. Two children in the halothane group did not develop flow-limited airway obstruction despite negative pressures as low as -9 cm H2O. Pcrit for sevoflurane ranged from -6.7 to -11.6 (mean +/- sd, -9.8 +/- 1.9) cm H2O. Pcrit for halothane ranged from -8.1 to -33 (mean +/- sd, -19.4 +/- 9.3) cm H2O (sevoflurane versus halothane, P = 0.048). We conclude that when using dynamic application of negative airway pressure, halothane appears to cause less upper airway obstruction than sevoflurane at equipotent concentrations.

  1. p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle

    NARCIS (Netherlands)

    Gosens, Reinoud; Dueck, Gordon; Gerthoffer, William T; Unruh, Helmut; Zaagsma, Johan; Meurs, Herman; Halayko, Andrew J

    2007-01-01

    Caveolae are abundant plasma membrane invaginations in airway smooth muscle that may function as preorganized signalosomes by sequestering and regulating proteins that control cell proliferation, including receptor tyrosine kinases (RTKs) and their signaling effectors. We previously demonstrated, ho

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

    Science.gov (United States)

    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...

  3. 呼吸康复方法对COPD气流受限患者呼吸功能的影响%Influence of respiratory rehabilitation method on respiratory function in COPD patients with airway obstruction

    Institute of Scientific and Technical Information of China (English)

    林文基; 唐文辉; 王嫚

    2015-01-01

    目的:探讨呼吸康复方法对COPD气流受限患者呼吸功能的影响。方法选取本院2012年10月~2014年10月收治的40例重度与极重度COPD稳定期患者作为研究对象,随机分成A组和B组,各20例。B组给予基础性药物治疗,A组在B组的基础上给予全面的呼吸康复方案,比较两组治疗前后的6 min步行距离(6 MWD)、Borg呼吸困难评分及肺通气功能各指标变化情况,记录其圣乔治呼吸问卷(SGRQ)评估结果。结果两组治疗后的Borg呼吸困难、SGRQ评分显著低于治疗前,两组治疗后的6 MWD显著长于治疗前,差异有统计学意义(P<0.05)。A组治疗后的6 MWD、SGRQ评分显著高于B组,Borg呼吸困难评分显著低于B组,差异有统计学意义(P<0.05)。两组治疗后的各项呼吸指标显著高于治疗前,差异有统计学意义(P<0.05)。A组治疗后的各项呼吸功指标显著高于B组,差异有统计学意义(P<0.05)。结论药物治疗联合呼吸康复方案治疗稳定期COPD效果显著,能够改善患者的肺通气功能,提高预后质量,值得临床推广应用。%Objective To explore the influence of respiratory rehabilitation method on respiratory function in chronic obstructive pulmonary disease (COPD) patients with airway obstruction. Methods 40 cases with severe and extremely severe COPD at a stable stage from October 2012 to October 2014 in our hospital were selected and randomly divided into group A) and group B,20 cases in each group.Group B was given basic drug therapy,group A was given compre-hensive respiratory rehabilitation regimen on the basis of Group B.The 6-minute walking distance (6 MWD),Borg dysp-nea score and the index change of pulmonary ventilation function before and after treatment in two groups was com-pared.The evaluated outcome of St.George’s respiratory questionnaire (SGRQ) was recorded. Results The score of Borg dyspnea and SGRQ in two groups after treatment than that after

  4. Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia.

    Science.gov (United States)

    Tan, Xiaojiang; Zhu, Song; Yan, Dongxing; Chen, Weiping; Chen, Ruilan; Zou, Jian; Yan, Jingdong; Zhang, Xiangdong; Farmakiotis, Dimitrios; Mylonakis, Eleftherios

    2016-08-01

    This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for ≥48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for ≥7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23% vs 15%, P=.01 and 34% vs. 15%, Pbaumannii VAP (29% vs. 21%, P=.153) but with higher in-hospital mortality (53% vs. 39%, P=.037). Candida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP.

  5. Visual Pattern Memory Requires "Foraging" Function in the Central Complex of "Drosophila"

    Science.gov (United States)

    Wang, Zhipeng; Pan, Yufeng; Li, Weizhe; Jiang, Huoqing; Chatzimanolis, Lazaros; Chang, Jianhong; Gong, Zhefeng; Liu, Li

    2008-01-01

    The role of the "foraging" ("for)" gene, which encodes a cyclic guanosine-3',5'-monophosphate (cGMP)-dependent protein kinase (PKG), in food-search behavior in "Drosophila" has been intensively studied. However, its functions in other complex behaviors have not been well-characterized. Here, we show experimentally in "Drosophila" that the "for"…

  6. A central body fat distribution is related to renal function impairment, even in lean subjects

    NARCIS (Netherlands)

    Pinto-Sietsma, SJ; Navis, G; Janssen, WMT; de Zeeuw, D; Gans, ROB; de Jong, PE

    2003-01-01

    Background Overweight and obesity are believed to be associated with renal damage. Whether this depends on fat distribution is not known. We hypothesize that in addition to overweight, fat distribution may be associated with renal function abnormalities. Methods: We studied the relation between body

  7. Pharmacology of airway afferent nerve activity

    Directory of Open Access Journals (Sweden)

    Carr Michael J

    2001-05-01

    Full Text Available Abstract Afferent nerves in the airways serve to regulate breathing pattern, cough, and airway autonomic neural tone. Pharmacologic agents that influence afferent nerve activity can be subclassified into compounds that modulate activity by indirect means (e.g. bronchial smooth muscle spasmogens and those that act directly on the nerves. Directly acting agents affect afferent nerve activity by interacting with various ion channels and receptors within the membrane of the afferent terminals. Whether by direct or indirect means, most compounds that enter the airspace will modify afferent nerve activity, and through this action alter airway physiology.

  8. Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.

    Directory of Open Access Journals (Sweden)

    Winfried Möller

    Full Text Available Endotoxin (Lipopolysaccharide, LPS is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h, Interleukin-6 (peaking at 6 h, body temperature (peaking at 12 h, and CRP (peaking at 24 h. 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1 and reactive oxygen production, assessed by hydrogen peroxide (H(2O(2 in fractionated exhaled breath condensate (EBC. FEV(1 showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2O(2 induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2O(2.Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.

  9. Mouth-opening increases upper-airway collapsibility without changing resistance during midazolam sedation.

    Science.gov (United States)

    Ayuse, T; Inazawa, T; Kurata, S; Okayasu, I; Sakamoto, E; Oi, K; Schneider, H; Schwartz, A R

    2004-09-01

    Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to -3.6 +/- 2.9 cm H2O compared with -8.7 +/- 2.8 (p = 0.002) for closed mouths and -7.2 +/- 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 +/- 6.6 vs. 17.7 +/- 7.6 vs. 21.5 +/- 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 +/- 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

  10. Ionotropic and Metabotropic Proton-Sensing Receptors Involved in Airway Inflammation in Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Haruka Aoki

    2014-01-01

    Full Text Available An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR, infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1 and acid-sensing ion channels (ASICs in severe acidic pH (of less than 6.0-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases.

  11. Fortified Settlements of the 9th and 10th Centuries ad in Central Europe: Structure, Function and Symbolism.

    Science.gov (United States)

    Herold, Hajnalka

    2012-11-01

    THE STRUCTURE, FUNCTION(S) and symbolism of early medieval (9th-10th centuries ad) fortified settlements from central Europe, in particular today's Austria, Hungary, Czech Republic and Slovakia, are examined in this paper. It offers an overview of the current state of research together with new insights based on analysis of the site of Gars-Thunau in Lower Austria. Special emphasis is given to the position of the fortified sites in the landscape, to the elements of the built environment and their spatial organisation, as well as to graves within the fortified area. The region under study was situated on the SE border of the Carolingian (and later the Ottonian) Empire, with some of the discussed sites lying in the territory of the 'Great Moravian Empire' in the 9th and 10th centuries. These sites can therefore provide important comparative data for researchers working in other parts of the Carolingian Empire and neighbouring regions.

  12. Technological Support of Estimating Functional Opportunities of Higher Parts of Central Nervous System in the Individuals with Auditory Deprivation

    Directory of Open Access Journals (Sweden)

    Makarenko M.V.

    2016-10-01

    Full Text Available A new computerized technology of investigating and estimating the individual features of higher parts of the central nervous system in people with auditory deprivation is offered. The essence of the offered technology for investigating and estimating individual functional opportunities of higher parts of the nervous system of an individual with auditory deprivation consists in using the specific sequence of representing the load tests with corresponding criteria of estimating the processed information of different level of complexity, which are applied on hardware devices developed by us. We represented the scales for estimating the parameters of simple and complex sensorimotor reactions, speed qualitative and quantitative indicators of processing information based on the typological properties of the nervous system, such as the functional mobility, strength and balance of basic nervous processes. We suppose that the research using the same tests and criteria of estimating neuro-dynamic properties will increase the opportunity for the analysis of different experimental material and enhance its value

  13. Abnormal liver function and central obesity associate with work-related fatigue among the Taiwanese workers

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Lin; Jong-Dar Chen; Chao-Jen Chen

    2008-01-01

    AIM: TO examine the associations between objective health indicators and high need for recovery (NFR) after work, one of the subjective presentations of work related-fatigue, among apparently healthy workers in modern workplaces. METHODS: From October to December, 2007, an annual health examination was performed for the workers from an electronics manufacturing factory in Taiwan. Health records of 1216 workers with a relatively homogeneous socioeconomic status were used for analysis. The health checkups included personal and NFR scale questionnaires, physical examinations, blood tests for biochemistry and hematology. The workers within the top tertile NFR score were defined as high-NFR workers. RESULTS: After adjusted for potential confounders, the workers with elevated alanine aminotransferase (ALT) and central obesity had a significantly higher NFR after work, with increased risks of 1.4-fold [95% confidence interval (CI) = 1.01-2.0] and 1.8-fold (95% CI = 1.2-2.7), respectively. Shiftworkers had a 2.0-fold (95% CI = 1.5-2.6) increased risk for high-NFR. The associations between high-NFR and lipid profiles, blood sugar, hematology indexes or blood pressure were insignificant after controlling for confounders. CONCLUSION: For apparently healthy workers, high NFR after work is not simply a subjective experience. Objective health measures, such as elevated ALT and increased waist circumference, should be carefully evaluated for the apparently healthy workers having a higher NFR after work.

  14. Functionality of Selected Aromatic Lamiaceae in Attracting Pollinators in Central Spain.

    Science.gov (United States)

    Barbir, Jelena; Azpiazu, Celeste; Badenes-Pérez, Francisco R; Fernández-Quintanilla, César; Dorado, José

    2016-04-01

    Planting floral margins in agricultural landscapes has been shown to increase the abundance of pollinators in agro-ecosystems. However, to create efficient margins, it is necessary to use attractive, not weedy native plants with different blooming periods to prolong the availability of floral resources. Six native perennial plants of the Lamiaceae with different blooming periods were studied in a randomized block design, with the final aim to select the most efficient plants in floral mixtures by studying relationships between their floral phenology, floral density, and attractiveness to pollinators in Central Spain. In addition, their spatial expansion, i.e., potential weediness, was estimated under the field conditions, as the final purpose of the plants is to be implemented within the agro-ecosystems. The results showed that plant species with higher floral density (Nepeta tuberosa L. and Hyssopus officinalis L.) showed significantly higher attractiveness to pollinators and enhanced the attractiveness of floral mixtures. Species that bloomed in early spring (Salvia verbenaca L.) and in summer (Melissa officinalis L. and Thymbra capitata L.) did not efficiently contribute to the attractiveness of the mixtures to pollinators. In addition, besides high floral density of Salvia officinalis L. and N. tuberosa in the spring, warm and dry weather in spring 2012 enhanced the activity of bees, while cold and rainy weather in spring 2013 enhanced the activity of hoverflies. None of the plants showed weedy growth and so posed no danger of invading adjacent crops.

  15. Pentraxin 3 (PTX3 expression in allergic asthmatic airways: role in airway smooth muscle migration and chemokine production.

    Directory of Open Access Journals (Sweden)

    Jingbo Zhang

    Full Text Available BACKGROUND: Pentraxin 3 (PTX3 is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 is produced by immune and structural cells. However, very little is known about the expression of PTX3 and its role in allergic asthma. OBJECTIVES AND METHODS: We sought to determine the PTX3 expression in asthmatic airways and its function in human airway smooth muscle cells (HASMC. In vivo PTX3 expression in bronchial biopsies of mild, moderate and severe asthmatics was analyzed by immunohistochemistry. PTX3 mRNA and protein were measured by real-time RT-PCR and ELISA, respectively. Proliferation and migration were examined using (3H-thymidine incorporation, cell count and Boyden chamber assays. RESULTS: PTX3 immunoreactivity was increased in bronchial tissues of allergic asthmatics compared to healthy controls, and mainly localized in the smooth muscle bundle. PTX3 protein was expressed constitutively by HASMC and was significantly up-regulated by TNF, and IL-1β but not by Th2 (IL-4, IL-9, IL-13, Th1 (IFN-γ, or Th-17 (IL-17 cytokines. In vitro, HASMC released significantly higher levels of PTX3 at the baseline and upon TNF stimulation compared to airway epithelial cells (EC. Moreover, PTX3 induced CCL11/eotaxin-1 release whilst inhibited the fibroblast growth factor-2 (FGF-2-driven HASMC chemotactic activity. CONCLUSIONS: Our data provide the first evidence that PTX3 expression is increased in asthmatic airways. HASMC can both produce and respond to PTX3. PTX3 is a potent inhibitor of HASMC migration induced by FGF-2 and can upregulate CCL11/eotaxin-1 release. These results raise the possibility that PTX3 may play a dual role in allergic asthma.

  16. Up-regulation of endothelin receptors induced by cigarette smoke--involvement of MAPK in vascular and airway hyper-reactivity

    DEFF Research Database (Denmark)

    Zhang, Yaping; Edvinsson, Lars; Xu, Cang-Bao

    2010-01-01

    and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm) and adverse proliferation......Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway...... (remodeling) of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen...

  17. Roles of LIM kinases in central nervous system function and dysfunction.

    Science.gov (United States)

    Cuberos, H; Vallée, B; Vourc'h, P; Tastet, J; Andres, C R; Bénédetti, H

    2015-12-21

    LIM kinase 1 (LIMK1) and LIM kinase 2 (LIMK2) regulate actin dynamics by phosphorylating cofilin. In this review, we outline studies that have shown an involvement of LIMKs in neuronal function and we detail some of the pathways and molecular mechanisms involving LIMKs in neurodevelopment and synaptic plasticity. We also review the involvement of LIMKs in neuronal diseases and emphasize the differences in the regulation of LIMKs expression and mode of action. We finally present the existence of a cofilin-independent pathway also involved in neuronal function. A better understanding of the differences between both LIMKs and of the precise molecular mechanisms involved in their mode of action and regulation is now required to improve our understanding of the physiopathology of the neuronal diseases associated with LIMKs.

  18. Lingual muscle activity across sleep-wake states in rats with surgically altered upper airway

    Directory of Open Access Journals (Sweden)

    Irma eRukhadze

    2014-04-01

    Full Text Available Obstructive sleep apnea (OSA patients have increased upper airway muscle activity, including such lingual muscles as the genioglossus (GG, geniohyoid (GH and hyoglossus (HG. This adaptation partially protects their upper airway against obstructions. Rodents are used to study the central neural control of sleep and breathing but they do not naturally exhibit OSA. We investigated whether, in chronically instrumented, behaving rats, disconnecting the GH and HG muscles from the hyoid (H apparatus would result in a compensatory increase of other upper airway muscle activity (EMG and/or other signs of upper airway instability. We first determined that, in intact rats, lingual (GG and intrinsic muscles maintained stable activity levels when quantified based on 2 h-long recordings conducted on days 6 through 22 after instrumentation. We then studied 5 rats in which the tendons connecting the GH and HG muscles to the H apparatus were experimentally severed. When quantified across all recording days, lingual EMG during SWS was modestly but significantly increased in rats with surgically altered upper airway (8.6% ±0.7(SE vs. 6.2% ±0.7 of the mean during wakefulness; p=0.012. Respiratory modulation of lingual EMG occurred mainly during SWS and was similarly infrequent in both groups, and the incidence of sighs and central apneas also was similar. Thus, a weakened action of selected lingual muscles did not produce sleep-disordered breathing but resulted in a relatively elevated activity in other lingual muscles during SWS. These results encourage more extensive surgical manipulations with the aim to obtain a rodent model with collapsible upper airway.

  19. Contribution of air pollution to COPD and small airway dysfunction.

    Science.gov (United States)

    Berend, Norbert

    2016-02-01

    Although in many Western countries levels of ambient air pollution have been improving with the setting of upper limits and better urban planning, air pollution in developing countries and particularly those with rapid industrialization has become a major global problem. Together with increased motor vehicle ownership and traffic congestion, there is a growing issue with airborne particles of respirable size. These particles are thought responsible for respiratory and cardiovascular effects and have also been implicated in cancer pathogenesis. The pathologic effects in the lung are mediated via inflammatory pathways and involve oxidative stress similar to cigarette smoking. These effects are seen in the peripheral airways where the smaller particle fractions are deposited and lead to airway remodelling. However, emphysema and loss of bronchioles seen with cigarette smoking have not been described with ambient air pollution, and there are few studies specifically looking at peripheral airway function. Definitive evidence of air pollution causing COPD is lacking and a different study design is required to link air pollution and COPD.

  20. [Airway clearance techniques in chronic obstructive pulmonary syndrome : 2011 update].

    Science.gov (United States)

    Opdekamp, C

    2011-09-01

    For many years the airway clearance techniques used in chest physical therapy were assimilated with the singular technique of postural drainage, percussions and vibrations. However the side effects and counter indications and the lack of scientific proof regarding this technique have forced reflection and development of other techniques more comfortable and without deleterious effects. If all these techniques show a high efficiency in terms of improved mucociliary clearance, the literature is unanimous on how little effect these techniques have in the short and the long-term with regards to lung function and arterial blood gases. In view of the scientific literature, it is clear that the airway clearance techniques don't have the same recognition concerning their efficiency in all obstructive pulmonary diseases. As the cornerstone in the management of cystic fibrosis, the efficiency of the bronchial hygiene techniques are in general poorly documented in the management of the non-cystic fibrosis bronchiectasis, bronchitis or emphysema. The use of the chest physical therapy seems more to do with the interpretation of the imagery and symptomatology. The airway clearance techniques should be individualised according to symptoms, the amount of expectorated mucus and the objectives signs of secretions retention or subjective signs of difficulty expectorating secretions with progression of the disease.

  1. Patterns of airway involvement in inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Ilias; Papanikolaou; Konstantinos; Kagouridis; Spyros; A; Papiris

    2014-01-01

    Extraintestinal manifestations occur commonly in inflammatory bowel diseases(IBD). Pulmonary manifestations(PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and highresolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheo-bronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency.

  2. Predictors of Airway Hyperresponsiveness in Elite Athletes

    DEFF Research Database (Denmark)

    Toennesen, Louise L; Porsbjerg, Celeste; Pedersen, Lars;

    2015-01-01

    INTRODUCTION: Elite athletes frequently suffer from asthma and airway hyperresponsiveness (AHR). We aimed to investigate predictors of airway pathophysiology in a group of unselected elite summer-sport athletes, training for the summer 2008 Olympic Games, including markers of airway inflammation......, systemic inflammation and training intensity. METHODS: 57 Danish elite summer-sport athletes with and without asthma symptoms all gave a blood sample for measurements of high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF....... In these subjects, no association was found between the levels of AHR to mannitol and methacholine (r=0.032, p=0.91). CONCLUSION: Airway hyperresponsiveness in elite athletes is related to the amount of weekly training and the level of serum TNF-α. No association was found between the level of AHR to mannitol...

  3. Muc5b is required for airway defence.

    Science.gov (United States)

    Roy, Michelle G; Livraghi-Butrico, Alessandra; Fletcher, Ashley A; McElwee, Melissa M; Evans, Scott E; Boerner, Ryan M; Alexander, Samantha N; Bellinghausen, Lindsey K; Song, Alfred S; Petrova, Youlia M; Tuvim, Michael J; Adachi, Roberto; Romo, Irlanda; Bordt, Andrea S; Bowden, M Gabriela; Sisson, Joseph H; Woodruff, Prescott G; Thornton, David J; Rousseau, Karine; De la Garza, Maria M; Moghaddam, Seyed J; Karmouty-Quintana, Harry; Blackburn, Michael R; Drouin, Scott M; Davis, C William; Terrell, Kristy A; Grubb, Barbara R; O'Neal, Wanda K; Flores, Sonia C; Cota-Gomez, Adela; Lozupone, Catherine A; Donnelly, Jody M; Watson, Alan M; Hennessy, Corinne E; Keith, Rebecca C; Yang, Ivana V; Barthel, Lea; Henson, Peter M; Janssen, William J; Schwartz, David A; Boucher, Richard C; Dickey, Burton F; Evans, Christopher M

    2014-01-16

    Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.

  4. System size and centrality dependence of the balance function in A+A collisions at $\\sqrt{s_NN}$ =172 GeV

    CERN Document Server

    Alt, C; Baatar, B; Barna, D; Bartke, Jerzy; Betev, L; Bialkowska, H; Billmeier, A; Blume, C; Boimska, B; Botje, M; Bracinik, J; Bramm, R; Brun, R; Buncic, P; Cerny, V; Christakoglou, P; Chvala, O; Cramer, J G; Csató, P; Darmenov, N; Dimitrov, A; Dinkelaker, P; Eckardt, V; Farantatos, G; Flierl, D; Fodor, Z; Foka, P; Freund, P; Friese, V; Gál, J; Gazdzicki, M; Georgopoulos, G; Gladysz-Dziadus, E; Grebieszkow, K; Hegyi, S; Höhne, C; Kadija, K; Karev, A; Kliemant, M; Kniege, S; Kolesnikov, V I; Kollegger, T; Kornas, E; Korus, R; Kowalski, M; Kraus, I; Kreps, M; Lévai, Peter; Litov, L; Lungwitz, B; Makariev, M; Malakhov, A I; Markert, C; Mateev, M; Mayes, B W; Melkumov, G L; Meurer, C; Mischke, A; Mitrovski, M; Molnár, J; Mrówczynski, S; Pálla, G; Panagiotou, A D; Panayotov, D; Petridis, A; Pikna, M; Pinsky, L; Pühlhofer, F; Reid, J G; Renfordt, R; Richard, A; Roland, C; Roland, G; Rybczynski, M; Rybicki, A; Sandoval, A; Sann, H; Schmitz, N; Seyboth, P; Siklér, F; Sitár, B; Skrzypczak, E; Stefanek, G; Stock, R; Ströbele, H; Susa, T; Szentpétery, I; Sziklai, J; Trubnikov, V; Varga, D; Vassiliou, Maria; Veres, G I; Vesztergombi, G; Vranic, D; Wetzler, A; Wlodarczyk, Z; Yoo, I K; Zaranek, J; Zimányi, J; Van Leeuwen, M

    2005-01-01

    Electric charge correlations were studied for p+p, C+C, Si+Si, and centrality selected Pb+Pb collisions at square root s/sub NN/=17.2 Ge V with the NA49 large acceptance detector at the CERN SPS. In particular, long-range pseudorapidity correlations of oppositely charged particles were measured using the balance function method. The width of the balance function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions.

  5. System Size and Centrality Dependence of the Balance Function in A + A Collisions at s(NN)^(1/2) = 17.2 GeV

    CERN Document Server

    Alt, C; Baatar, B; Barna, D; Bartke, Jerzy; Betev, L; Bial, H; Billmeier, A; Blume, C; Boimska, B; Botje, M; Bracinik, J; Bramm, R; Brun, R; Buncic, P; Cerny, V; Christakoglou, P; Chvala, O; Cramer, J G; Csató, P; Darmenov, N; Dimitrov, A; Dinkelaker, P; Eckardt, V; Farantatos, G; Flierl, D; Fodor, Z; Foka, P; Freund, P; Friese, V; Gál, J; Gazdzicki, M; Georgopoulos, G; Gladysz-Dziadus, E; Grebieszkow, K; Hegyi, S; Höhne, C; Kadija, K; Karev, A; Kliemant, M; Kniege, S; Kolesnikov, V I; Kollegger, T; Kornas, E; Korus, R; Kowalski, M; Kraus, I; Kreps, M; Van Leeuwen, M; Lévai, Peter; Litov, L; Lungwitz, B; Makariev, M; Malakhov, A I; Markert, C; Mateev, M; Mayes, B W; Melkumov, G L; Meurer, C; Mischke, A; Mitrovski, M; Molnár, J; Mrówczynski, S; Pálla, G; Panagiotou, A D; Panayotov, D; Petridis, A; Pikna, M; Pinsky, L; Pühlhofer, F; Reid, J G; Renfordt, R E; Richard, A; Roland, C; Roland, G; Rybczynski, M; Rybicki, A; Sandoval, A; Sann, H; Schmitz, N; Seyboth, P; Siklér, F; Sitár, B; Skrzypczak, E; Stefanek, G; Stock, R; Ströbele, H; Susa, T; Szentpétery, I; Sziklai, J; Trubnikov, V; Varga, D; Vassiliou, Maria; Veres, G I; Vesztergombi, G; Vranic, D; Wetzler, A; Wlodarczyk, Z; Yoo, I K; Zaranek, J; Zimányi, J

    2004-01-01

    Electric charge correlations were studied for p+p, C+C, Si+Si and centrality selected Pb+Pb collisions at $\\sqrt{s_{NN}} = 17.2$ GeV with the NA49 large acceptance detector at the CERN-SPS. In particular, long range pseudo-rapidity correlations of oppositely charged particles were measured using the Balance Function method. The width of the Balance Function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions.

  6. Effects of iron deficiency on cognitive function in school going adolescent females in rural area of central India.

    Science.gov (United States)

    More, Sarika; Shivkumar, V B; Gangane, Nitin; Shende, Sumeet

    2013-01-01

    Iron deficiency anemia is most common nutritional deficiency disorder in India and remains a formidable health challenge. Girls in the period of later school age and early adolescence are prone to develop iron deficiency. Iron deficiency leads to many non-hematological disturbances which include growth and development, depressed immune function in infants; reduces physical work capacity; decreases the cognitive function in both infants and adolescents. Present study was done to know the prevalence of iron deficiency in both the anemic and non anemic school going adolescent girls, to assess the effect of iron deficiency on cognitive functions in anemic iron deficient and non-anemic iron deficient school girls in a village school situated in central India. Methods. A secondary school having girl students in the age group of 12-15 years studying in sixth to ninth standard was selected. Serum ferritin concentration was estimated by ELISA. For assessing the cognitive function mathematics score, one multi-component test for memory, attention and verbal learning and Intelligent Quotient scores of the students were used. Results. Scholastic Performance, IQ and Scores of Mental balance, Attention & Concentration, Verbal Memory and Recognition were decreased in iron deficient girls, both anemic and non anemic as compared to the non iron deficient girls.

  7. Autism and genius: is there a link? The involvement of central brain loops and hypotheses for functional testing.

    Science.gov (United States)

    Boso, M; Emanuele, E; Prestori, Francesca; Politi, P; Barale, F; D'Angelo, E

    2010-01-01

    Mental processing is the product of the huge number of synaptic interactions that occur in the brain. It is easier to understand how brain functions can deteriorate than how they might be boosted. Lying at the border between the humanities, cognitive science and neurophysiology, some mental diseases offer new angles on this problematic issue. Despite their social deficits, autistic subjects can display unexpected and extraordinary skills in numerous fields, including music, the arts, calculation and memory. The advanced skills found in a subgroup of people with autism may be explained by their special mental functioning, in particular by their weak central coherence, one of the pivotal characteristics of the disorder. As a result of the increasing interest in autistic talent, there has recently emerged a tendency to screen any eccentric artist or scientist for traits of the autistic spectrum. Following this trend, we analyze the eccentricity of the popular pianist Glenn Gould and briefly discuss the major functional hypotheses on autistic hyperfunctioning, advancing proposals for functional testing. In particular, the potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens up new perspectives for the investigation of autistic disorders and brain hyperfunctioning.

  8. Response of ants to grazing disturbance at the central Monte Desert of Argentina:community descriptors and functional group scheme

    Institute of Scientific and Technical Information of China (English)

    Silvia CLAVER; Susana L SILNIK; Florencia F CAMPÓN

    2014-01-01

    Livestock ranching is one of the main productive activities in arid regions of the world. Grazing pro-duces changes in animal as well as plant communities (e.g. richness, abundance and species dominance rela-tionships). Ants are good biological indicators due to the environmental fidelity of some of their community pa-rameters. We described the functional structure of the ant community in the central Monte of Mendoza, Argentina, and examined the effect of grazing using richness, diversity and the functional group scheme. We used pitfall traps to sample ants at a reserve with 30-year cattle exclusion and at an adjacent ranch. Eleven of the 27 recorded spe-cies showed significant differences in their abundance and two species were absent at the ranch. While richness and diversity did not reflect these differences, functional groups did. Hot Climate Specialists were more abundant at the ranch while Cryptic Species and Generalized Myrmicinae increased at the reserve. This study supports the utility of the functional group scheme to study the effects of grazing disturbance in ant communities of arid regions.

  9. Braquiterapia endobronquial de alta tasa de dosis en pacientes con obstrucción de la vía aérea central: Experiencia en el Instituto Nacional del Cáncer y revisión de la literatura High dose rate endobronchial brachytherapy in patients with central airway obstruction

    Directory of Open Access Journals (Sweden)

    ALEJANDRO SANTINI B

    2010-09-01

    Full Text Available Introducción: La indicación principal de la braquiterapia endobronquial moderna (BTEB de alta tasa de dosis (HDR, es la paliación de síntomas por crecimiento endobronquial de cánceres pulmonares. Métodos: Se realizó BTEB HDR a 27 pacientes sintomáticos de patología tumoral endobronquial o traqueal, debido a patologías primarias bronquiales o secundarias metastásicas. Los tumores se ubicaban en tráquea, carina o a nivel bronquialproximal. Para observar mejorías en la sintomatología clínica, a todos se les realizó una fibrobroncoscopía (FBC para medir el grado de obstrucción bronquial e instalar catéteres endobronquiales de braquiterapia. Se administraron entre 1 y 4 fracciones de 7 a 7,5 Gy. Se registró subjetivamente la disnea, tos y hemoptisis antes y después del tratamiento, de acuerdo a una escala internacionalmente validada. Resultados: Tras el tratamiento todos los síntomas disminuyeron considerablemente, desapareciendo toda sintomatología severa. La hemoptisis y disnea desaparecieron en el 100% y 40% de los pacientes respectivamente, y la tos desapareció o disminuyó a grado leve en el 90% de los pacientes.Introduction: The main indication of modern high dose rate end bronchial brachyherapy (HDR EBBT is the palliation of symptoms related to the growth of the endobronchial lung cancer. Methods: EBBT was performed to 27 patients who suffered symptomatic tumoral endobronchial or tracheal pathology, due to primary bronchial disease or secondary metastasis cancer, evaluating the rate of clinical benefit. The tumors were located at tracheal, carinal or proximal bronchial level. Fibrobronchoscopy was performed to all the patients to measure the degree of airway obstruction and to install brachytherapy endobronchial catheters. Between 1 to 4 fractions of 7 to 7.5 Gy were administered. Dyspnea, cough and hemoptysis were subjectively registered before and after treatment, according to an international validated scale. Results

  10. Contribution of central versus sweat gland mechanisms to the seasonal change of sweating function in young sedentary males and females

    Science.gov (United States)

    Taniguchi, Yumiko; Sugenoya, Junichi; Nishimura, Naoki; Iwase, Satoshi; Matsumoto, Takaaki; Shimizu, Yuuki; Inukai, Yoko; Sato, Maki

    2011-03-01

    In summer and winter, young, sedentary male ( N = 5) and female ( N = 7) subjects were exposed to heat in a climate chamber in which ambient temperature (Ta) was raised continuously from 30 to 42°C at a rate of 0.1°C min-1 at a relative humidity of 40%. Sweat rates (SR) were measured continuously on forearm, chest and forehead together with tympanic temperature (Tty), mean skin temperature ( {overline {{T}} {{s}}} ) and mean body temperature ( {overline {{T}} {{b}}} ) . The rate of sweat expulsions (Fsw) was obtained as an indicator of central sudomotor activity. Tty and ( {overline {{T}} {{b}}} ) were significantly lower during summer compared with winter in males; SR was not significantly different between summer and winter in males, but was significantly higher during summer in females; SR during winter was higher in males compared with females. The regression line relating Fsw to ( {overline {{T}} {{b}}} ) shifted significantly from winter to summer in males and females, but the magnitude of the shift was not significantly different between the two subject groups. The regression line relating SR to Fsw was steepened significantly from winter to summer in males and females, and the change in the slope was significantly greater in females than in males. Females showed a lower slope in winter and a similar slope in summer compared to males. It was concluded that sweating function was improved during summer mediated by central sudomotor and sweat gland mechanisms in males and females, and, although the change of sweat gland function from winter to summer was greater in females as compared with males, the level of increased sweat gland function during summer was similar between the two subject groups.

  11. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control

    Directory of Open Access Journals (Sweden)

    Ai-Fen Yan

    2016-05-01

    Full Text Available In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC. By intraperitoneal (IP injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY injection. High levels of leptin receptor (lepR mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART, cholecystokinin (CCK, melanin-concentrating hormone (MCH and proopiomelanocortin (POMC in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model.

  12. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control.

    Science.gov (United States)

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-05-30

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model.

  13. Environmental and genetical factors in airway allergies

    OpenAIRE

    Katarzyna Idzik

    2012-01-01

    It is estimated that approximately 23% of the European population is clinically diagnosed with allergies. In the past three decades, an increase in the incidence of respiratory allergies was noted. At the beginning of the 20th century allergic inflammations affected only around 1% of the world population. Medical symptoms of allergic airway inflammation are variable for different patients. Airways allergy are complex phenotypes, which are determined by both genetic and...

  14. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients.

    Science.gov (United States)

    Cox, Michael J; Allgaier, Martin; Taylor, Byron; Baek, Marshall S; Huang, Yvonne J; Daly, Rebecca A; Karaoz, Ulas; Andersen, Gary L; Brown, Ronald; Fujimura, Kei E; Wu, Brian; Tran, Diem; Koff, Jonathan; Kleinhenz, Mary Ellen; Nielson, Dennis; Brodie, Eoin L; Lynch, Susan V

    2010-06-23

    Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

  15. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Michael J Cox

    Full Text Available Bacterial communities in the airways of cystic fibrosis (CF patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months to adults (72 years. From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

  16. Ultrasound: A novel tool for airway imaging

    Directory of Open Access Journals (Sweden)

    Siddharthkumar Bhikhabhai Parmar

    2014-01-01

    Full Text Available Context: The scope of ultrasound is emerging in medical science, particularly outside traditional areas of radiology practice. Aims: We designed this study to evaluate feasibility of bedside sonography as a tool for airway assessment and to describe sonographic anatomy of airway. Settings and Design: A prospective, clinical study. Materials and Methods: We included 100 adult, healthy volunteers of either sex to undergo airway imaging systemically starting from floor of the mouth to the sternal notch in anterior aspect of neck by sonography. Results: We could visualize mandible and hyoid bone as a bright hyperechoic structure with hypoechoic acoustic shadow underneath. Epiglottis, thyroid cartilage, cricoid cartilage, and tracheal rings appeared hypoechoic. Vocal cords were visualized through thyroid cartilage. Interface between air and mucosa lining the airway produced a bright hyperechoic linear appearance. Artifacts created by intraluminal air prevented visualization of posterior pharynx, posterior commissure, and posterior wall of trachea. Conclusions: Ultrasound is safe, quick, noninvasive, repeatable, and bedside tool to assess the airway and can provide real-time dynamic images relevant for several aspects of airway management.

  17. The laryngeal mask airway at altitude.

    Science.gov (United States)

    Wilson, Grant D; Sittig, Steven E; Schears, Gregory J

    2008-02-01

    The Laryngeal Mask Airway (LMA) is an accepted adjunct for airway management in emergency patients. There are a number of case reports describing its use in transport medicine for infant to adult patients, including during flight. Although studies of the effect altitude has on air-filled tracheal tubes exists, we were unable to find documentation of the effect of altitude on laryngeal mask airways. Our objective was to assess the effect of altitude on the LMA in both fixed wing and rotary wing models. We performed an in vitro study of the effect of altitude on the LMA cuff. Infant and adult airway trainer mannequins with properly sized and inserted LMA-Classic laryngeal mask airways were monitored for cuff pressure changes while flown at altitudes commonly encountered during air medical transport. Both models demonstrated that LMA cuff pressures may exceed manufacturer recommended levels for safe use even at the relatively low altitudes experienced during rotor wing flight. Properly inserted and inflated laryngeal mask airways at ground level may result in overinflated LMA cuffs when flown to altitudes commonly used for rotor and fixed wing medical transport unless monitored and corrected.

  18. Effects of Sweet Bee Venom on the Central Nervous System in Rats -using the Functional Observational Battery-

    Directory of Open Access Journals (Sweden)

    Joong Chul An

    2011-09-01

    Full Text Available Objectives: This study was performed to analyse the effects of Sweet Bee Venom(Sweet BV-pure melittin, the major component of honey bee venom on the central nervous system in rats. Methods: All experiments were conducted at Biotoxtech Company, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP. Male rats of 5 weeks old were chosen for this study and after confirming condition of rats was stable, Sweet BV was administered in thigh muscle of rats. And checked the effects of Sweet BV on the central nervous system using the functional observational battery (FOB, which is a neuro-toxicity screening assay composed of 30 descriptive, scalar, binary, and continuous endpoints. And home cage observations, home cage removal and handling, open field activity, sensorimotor reflex test/physiological measurements were conducted. Results: 1. In the home cage observation, there was not observed any abnormal signs in rats. 2. In the observation of open field activity, the reduction of number of unit areas crossed and rearing count was observed caused by Sweet BV treatment. 3. In the observation of handling reactivity, there was not observed any abnormal signs in rats. 4. In the observation of sensorimotor reflex tests/physiological measurements, there was not observed any neurotoxic signs in rats. 5. In the measurement of rectal temperature, treatment of Sweet BV did not showed great influences in the body temperature of rats. Conclusions: Above findings suggest that Sweet BV is relatively safe treatment in the central nervous system. But in the using of over dose, Sweet BV may the cause of local pain and disturbance of movement. Further studies on the subject should be conducted to yield more concrete evidences.

  19. Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids

    NARCIS (Netherlands)

    Kunz, Lisette I Z; Ten Hacken, Nick H T; Lapperre, Thérèse S; Timens, Wim; Kerstjens, Huib A M; van Schadewijk, Annemarie; Vonk, Judith M; Sont, Jacob K; Snoeck-Stroband, Jiska B; Postma, Dirkje S; Sterk, Peter J; Hiemstra, Pieter S

    2017-01-01

    Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that

  20. Mechanisms determining cholinergic neural responses in airways of young and mature rabbits.

    Science.gov (United States)

    Larsen, Gary L; Loader, Joan; Nguyen, Dee Dee; Fratelli, Cori; Dakhama, Azzeddine; Colasurdo, Giuseppe N

    2004-08-01

    Neural pathways help control airway caliber and responsiveness. Yet little is known of how neural control changes as a function of development. In rabbits, we found electrical field stimulation (EFS) of airway nerves led to more marked contractile responses in 2- vs. 13-week-old animals. This enhanced response to EFS may be due to prejunctional, junctional, and/or postjunctional neural mechanisms. We assessed these mechanisms in airways of 2- and 13-week-old rabbits. The contractile responses to methacholine did not differ in the groups, suggesting postjunctional neural events are not primarily responsible for differing responses to EFS. To address junctional events, acetylcholinesterase (AChE) was measured (spectrophotometry). AChE was elevated in 2-week-olds. However, this should lead to less and not greater responses. Prejunctionally, EFS-induced acetylcholine (ACh) release was assessed by HPLC. Airways of 2-week-old rabbits released significantly more ACh than airways from mature rabbits. Choline acetyltransferase, a marker of cholinergic nerves, was not different between groups, suggesting that more ACh release in young rabbits was not due to increased nerve density. ACh release in the presence of polyarginine increased significantly in both groups, supporting the presence of functional muscarinic autoreceptors (M2) at both ages. Because substance P (SP) increases release of ACh, SP was measured by ELISA. This neuropeptide was significantly elevated in airways of younger rabbits. Nerve growth factor (NGF) increased SP and was also significantly increased in airways from younger rabbits. This work suggests that increases in EFS-induced responsiveness in young rabbits are likely due to prejunctional events with enhanced release of ACh. Increases in NGF and SP early in life may contribute to this increased responsiveness.

  1. Lung hyperinflation and its reversibility in patients with airway obstruction of varying severity.

    Science.gov (United States)

    Deesomchok, Athavudh; Webb, Katherine A; Forkert, Lutz; Lam, Yuk-Miu; Ofir, Dror; Jensen, Dennis; O'Donnell, Denis E

    2010-12-01

    The natural history of lung hyperinflation in patients with airway obstruction is unknown. In particular, little information exists about the extent of air trapping and its reversibility to bronchodilator therapy in those with mild airway obstruction. We completed a retrospective analysis of data from individuals with airway obstruction who attended our pulmonary function laboratory and had plethysmographic lung volume measurements pre- and post-bronchodilator (salbutamol). COPD was likely the predominant diagnosis but patients with asthma may have been included. We studied 2,265 subjects (61% male), age 65 ± 9 years (mean ± SD) with a post-bronchodilator FEV(1)/FVC lung hyperinflation, and measured responses to bronchodilation across subgroups stratified by GOLD criteria. In GOLD stage I, vital capacity (VC) and inspiratory capacity (IC) were in the normal range; pre-bronchodilator residual volume (RV), functional residual capacity (FRC) and specific airway resistance were increased to 135%, 119% and 250% of predicted, respectively. For the group as a whole, RV and FRC increased exponentially as FEV(1) decreased, while VC and IC decreased linearly. Regardless of baseline FEV(1), the most consistent improvement following bronchodilation was RV reduction, in terms of magnitude and responder rate. In conclusion, increases (above normal) in airway resistance and plethysmographic lung volumes were found in those with only minor airway obstruction. Indices of lung hyperinflation increased exponentially as airway obstruction worsened. Those with the greatest resting lung hyperinflation showed the largest bronchodilator-induced volume deflation effects. Reduced air trapping was the predominant response to acute bronchodilation across severity subgroups.

  2. Numerical modeling of the central Black Sea ecosystem functioning during the eutrophication phase

    Science.gov (United States)

    Grégoire, M.; Raick, C.; Soetaert, K.

    2008-03-01

    A one-dimensional coupled physical-biogeochemical model has been developed to simulate the ecosystem of the central Black Sea at the end of the 1980s when eutrophication and invasion by gelatinous organisms seriously affected the stability and dynamics of the system. The physical model is the General Ocean Turbulence Model (GOTM) and the biogeochemical model describes the foodweb from bacteria to gelatinous carnivores through 24 state variables including three groups of phytoplankton: diatoms, small phototrophic flagellates and dinoflagellates, two zooplankton groups: micro- and mesozooplankton, two groups of gelatinous zooplankton: the omnivorous and carnivorous forms, an explicit representation of the bacterial loop: bacteria, labile and semi-labile dissolved organic matter, particulate organic matter. The model simulates oxygen, nitrogen, silicate and carbon cycling. In addition, an innovation of this model is that it explicitly represents processes in the anoxic layer. Biogeochemical processes in anaerobic conditions have been represented using an approach similar to that used in the modeling of diagenetic processes in the sediments lumping together all the reduced substances in one state variable [Soetaert, K., Herman, P., 1996. A model of early diagenetic processes from the shelf to abyssal depths. Geochimica et Cosmochimica Acta 60 (6) 1019-1040]. In this way, processes in the upper oxygenated layer are fully coupled with anaerobic processes in the deep waters, allowing to perform longterm simulations. The mathematical modeling of phytoplankton and zooplankton dynamics, detritus and the microbial loop is based on the model developed by Van den Meersche et al. [Van den Meersche, K., Middelburg, J., Soetaert, K., van Rijswijk P.H.B., Heip, C., 2004. Carbon-nitrogen coupling and algal-bacterial interactions during an experimental bloom: Modeling a 13c tracer experiment. Limnology and Oceanography 49 (3), 862-878] and tested in the modeling of mesocosm

  3. Integrity of central nervous function in diabetes mellitus assessed by resting state EEG frequency analysis and source localization

    DEFF Research Database (Denmark)

    Frøkjær, Jens B; Graversen, Carina; Brock, Christina;

    2016-01-01

    localization analysis identified sources with reduced activity in the left postcentral gyrus for the gamma band and in right superior parietal lobule for the alpha1 (8-10Hz) band. DM patients with clinical signs of autonomic dysfunction and gastrointestinal symptoms had evidence of altered resting state......Diabetes mellitus (DM) is associated with structural and functional changes of the central nervous system. We used electroencephalography (EEG) to assess resting state cortical activity and explored associations to relevant clinical features. Multichannel resting state EEG was recorded in 27...... healthy controls and 24 patients with longstanding DM and signs of autonomic dysfunction. The power distribution based on wavelet analysis was summarized into frequency bands with corresponding topographic mapping. Source localization analysis was applied to explore the electrical cortical sources...

  4. Effects of cognitive training on resting-state functional connectivity of default mode, salience and central executive networks

    Directory of Open Access Journals (Sweden)

    Weifang eCao

    2016-04-01

    Full Text Available Neuroimaging studies have documented that ageing can disrupt certain higher cognitive systems such as the default mode network (DMN, the salience network (SN and the central executive network (CEN. The effect of cognitive training on higher cognitive systems remains unclear. This study used a one-year longitudinal design to explore the cognitive training effect on three higher cognitive networks in healthy older adults. The community-living healthy older adults were divided into two groups: the multi-domain cognitive training group (24 sessions of cognitive training over a three-month period and the wait-list control group. All subjects underwent cognitive measurements and resting-state functional magnetic resonance imaging (fMRI scanning at baseline and at one year after the training ended. We examined training-related changes in functional connectivity (FC within and between three networks. Compared with the baseline, we observed maintained or increased FC within all three networks after training. The scans after training also showed maintained anti-correlation of FC between the DMN and CEN compared to the baseline. These findings demonstrated that cognitive training maintained or improved the functional integration within networks and the coupling between the DMN and CEN in older adults. Our findings suggested that multi-domain cognitive training can mitigate the ageing-related dysfunction of higher cognitive networks.

  5. Magnetic transfer function entropy and the 2009 Mw = 6.3 L'Aquila earthquake (Central Italy

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    L. X. Wu

    2012-07-01

    Full Text Available With the aim of obtaining a deeper knowledge of the physical phenomena associated with the 2009 L'Aquila (Central Italy seismic sequence, culminating with a Mw = 6.3 earthquake on 6 April 2009, and possibly of identifying some kind of earthquake-related magnetic or geoelectric anomaly, we analyse the geomagnetic field components measured at the magnetic observatory of L'Aquila and their variations in time. In particular, trends of magnetic transfer functions in the years 2006–2010 are inspected. They are calculated from the horizontal to vertical magnetic component ratio in the frequency domain, and are very sensitive to deep and lateral geoelectric characteristics of the measurement site. Entropy analysis, carried out from the transfer functions with the so called transfer function entropy, points out clear temporal burst regimes of a few distinct harmonics preceding the main shock of the seismic sequence. A possible explanation is that they could be related to deep fluid migrations and/or to variations in the micro-/meso-fracturing that affected significantly the conductivity (ordered/disordered distribution in a large lithospheric volume under the seismogenic layer below L'Aquila area. This interpretation is also supported by the analysis of hypocentres depths before the main shock occurrence.

  6. Preliminary Results From the CAUGHT Experiment: Investigation of the North Central Andes Subsurface Using Receiver Functions and Ambient Noise Tomography

    Science.gov (United States)

    Ryan, J. C.; Ward, K. M.; Porter, R. C.; Beck, S. L.; Zandt, G.; Wagner, L. S.; Minaya, E.; Tavera, H.

    2011-12-01

    Jamie Ryan, Kevin M. Ward, Ryan Porter, Susan Beck, George Zandt, Lara Wagner, Estela Minaya, and Hernando Tavera The University of Arizona The University of North Carolina San Calixto Observatorio, La Paz, Bolivia IGP, Lima, Peru In order to investigate the interplay between crustal shortening, lithospheric removal, and surface uplift we have deployed 50 broadband seismometers in northwestern Bolivia and southern Peru as part of the interdisciplinary Central Andean Uplift and Geodynamics of High Topography (CAUGHT) project. The morphotectonic units of the central Andes from west to east, consist of the Western Cordillera, the active volcanic arc, the Altiplano, an internally drained basin (~4 km elevation), the Eastern Cordillera, the high peaks (~6 km elevation) of an older fold and thrust belt, the Subandean zone, the lower elevation active fold and thrust belt, and the foreland Beni basin. Between northwestern Bolivia and southern Peru, the Altiplano pinches out north of Lake Titicaca as the Andes narrow northward. The CAUGHT seismic instruments were deployed between 13° to 18° S latitudes to investigate the crust and mantle lithosphere of the central Andes in this transitional zone. In northwest Bolivia, perpendicular to the strike of the Andes, there is a total of 275 km of documented upper crustal shortening (15° to 17°S) (McQuarrie et al, 2008). Associated with the shortening is crustal thickening and possibly lithospheric removal as the thickening lithospheric root becomes unstable. An important first order study is to compare upper crustal shortening estimates with present day crustal thickness. To estimate crustal thickness, we have calculated receiver functions using an iterative deconvolution method and used common conversion point stacking along the same profile as the geologically based shortening estimates. In our preliminary results, we observed a strong P to S conversion corresponding to the Moho at approximately 60-65 km depth underneath the

  7. Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Bachert, Claus; Konge, Lars;

    2015-01-01

    Background It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii) bro...

  8. Full Airway Drainage by Fiber Bronchoscopy Through Artificial Airway in the Treatment of Occult Traumatic Atelectasis.

    Science.gov (United States)

    Zhao, Xue Hong; Zhang, Yun; Liang, Zhong Yan; Zhang, Shao Yang; Yu, Wen Qiao; Huang, Fang-Fang

    2015-12-01

    The objective of this study is to investigate the effects of full airway drainage by fiber bronchoscopy through artificial airway in the treatment of traumatic atelectasis with occult manifestations. From May 2006 to May 2011, 40 cases of occult traumatic atelectasis were enrolled into our prospective study. Group A (n = 18) received drainage by nasal bronchoscope; group B underwent airway drainage by fiber bronchoscopy through artificial airway (n = 22). The effects of treatment were evaluated by the incidence of adult respiratory distress syndrome (ARDS), lung abscess, and the average length of hospital stay. Compared with nasal fiber-optic treatment, airway drainage by fiber bronchoscopy through artificial airway reduced the incidence of ARDS (p = 0.013) and lung abscess (p = 0.062) and shortened the mean length of stay (p = 0.018). Making the decision to create an artificial airway timely and carry out lung lavage by fiber bronchoscopy through artificial airway played a significant role in the treatment of occult traumatic atelectasis.

  9. 75 FR 13079 - Action Affecting Export Privileges; MAHAN AIRWAYS; Mahan Airways, Mahan Tower, No. 21, Azadegan...

    Science.gov (United States)

    2010-03-18

    ... Secretary Jackson issued an Order adding Blue Airways FZE and Blue Airways, both of Dubai, United Arab... conduct illustrates its refusal to comply with the TDO or U.S. export control laws.\\6\\ \\6\\ My findings are... full written statement in support of the appeal with the Office of the Administrative Law Judge,...

  10. Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Bachert, Claus; Konge, Lars;

    2015-01-01

    Background It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii...

  11. Lipocalin2 protects against airway inflammation and hyperresponsiveness in a murine model of allergic airway disease

    DEFF Research Database (Denmark)

    Dittrich, A M; Krokowski, M; Meyer, H-A;

    2010-01-01

    Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways.......Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways....

  12. Smooth muscle in human bronchi is disposed to resist airway distension.

    Science.gov (United States)

    Gazzola, Morgan; Henry, Cyndi; Couture, Christian; Marsolais, David; King, Gregory G; Fredberg, Jeffrey J; Bossé, Ynuk

    2016-07-15

    Studying airway smooth muscle (ASM) in conditions that emulate the in vivo environment within which the bronchi normally operate may provide important clues regarding its elusive physiological function. The present study examines the effect of lengthening and shortening of ASM on tension development in human bronchial segments. ASM from each bronchial segment was set at a length approximating in situ length (Linsitu). Bronchial tension was then measured during a slow cyclical strain (0.004Hz, from 0.7Linsitu to 1.3Linsitu) in the relaxed state and at graded levels of activation by methacholine. In all cases, tension was greater at longer ASM lengths, and greater during lengthening than shortening. The threshold of methacholine concentration that was required for ASM to account for bronchial tension across the entire range of ASM lengths tested was on average smaller by 2.8 logs during lengthening than during shortening. The length-dependency of ASM tension, together with this lower threshold of methacholine concentration during lengthening versus shortening, suggest that ASM has a greater ability to resist airway dilation during lung inflation than to narrow the airways during lung deflation. More than serving to narrow the airway, as has long been thought, these data suggest that the main function of ASM contraction is to limit airway wall distension during lung inflation.

  13. Epithelial cell-extracellular matrix interactions and stem cells in airway epithelial regeneration.

    Science.gov (United States)

    Coraux, Christelle; Roux, Jacqueline; Jolly, Thomas; Birembaut, Philippe

    2008-08-15

    In healthy subjects, the respiratory epithelium forms a continuous lining to the airways and to the environment, and plays a unique role as a barrier against external deleterious agents to protect the airways from the insults. In respiratory diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), chronic bronchitis, or asthma, the airway epithelium is frequently remodeled and injured, leading to the impairment of its defense functions. The rapid restoration of the epithelial barrier is crucial for these patients. The complete regeneration of the airway epithelium is a complex phenomenon, including not only the epithelial wound repair but also the epithelial differentiation to reconstitute a fully well differentiated and functional epithelium. The regeneration implies two partners: the epithelial stem/progenitor cells and factors able to regulate this process. Among these factors, epithelial cells-extracellular matrix (ECM) interactions play a crucial role. The secretion of a provisional ECM, the cell-ECM relationships through epithelial receptors, and the remodeling of the ECM by proteases (mainly matrix metalloproteinases) contribute not only to airway epithelial repair by modulating epithelial cell migration and proliferation, but also to the differentiation of repairing cells leading to the complete restoration of the wounded epithelium. A better characterization of resident stem cells and of effectors of the regeneration process is an essential prerequisite to propose new regenerative therapeutics to patients suffering from infectious/inflammatory respiratory diseases.

  14. Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation

    Science.gov (United States)

    Vladar, Eszter K.; Nayak, Jayakar V.; Milla, Carlos E.; Axelrod, Jeffrey D.

    2016-01-01

    Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease. PMID:27570836

  15. Temporal correlation of optical coherence tomography in-vivo images of rabbit airway for the diagnosis of edema

    Science.gov (United States)

    Kang, DongYel; Wang, Alex; Tjoa, Tjoson; Volgger, Veronika; Hamamoto, Ashley; Su, Erica; Jing, Joseph; Chen, Zhongping; Wong, Brian J. F.

    2014-03-01

    Recently, full-range optical coherence tomography (OCT) systems have been developed to image the human airway. These novel systems utilize a fiber-based OCT probe which acquires three-dimensional (3-D) images with micrometer resolution. Following an airway injury, mucosal edema is the first step in the body's inflammatory response, which occasionally leads to airway stenosis, a life-threatening condition for critically ill newborns. Therefore, early detection of edema is vital for airway management and prevention of stenosis. In order to examine the potential of the full-range OCT to diagnose edema, we investigated temporal correlation of OCT images obtained from the subglottic airway of live rabbits. Temporally correlated OCT images were acquired at fixed locations in the rabbit subglottis of either artificially induced edema or normal tissues. Edematous tissue was experimentally modeled by injecting saline beneath the epithelial layer of the subglottic mucosa. The calculated cross temporal correlations between OCT images of normal airway regions show periodicity that correlates with the respiratory motion of the airway. However, the temporal correlation functions calculated from OCT images of the edematous regions show randomness without the periodic characteristic. These in-vivo experimental results of temporal correlations between OCT images show the potential of a computer-based or -aided diagnosis of edema in the human respiratory mucosa with a full-range OCT system.

  16. 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

  17. Functional results from reconstruction of the anterior cruciate ligament using the central third of the patellar ligament and flexor tendons

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    Marcos George de Souza Leao

    2015-12-01

    Full Text Available ABSTRACT OBJECTIVES: To evaluate knee function in patients undergoing reconstruction of the anterior cruciate ligament (ACL using the central third of the patellar ligament or the medial flexor tendons of the knee, i.e. quadruple ligaments from the semitendinosus and gracilis (ST-G, by means of the Knee Society Score (KSS and the Lysholm scale. METHODS: This was a randomized prospective longitudinal study on 40 patients who underwent arthroscopic ACL reconstruction between September 2013 and August 2014. They comprised 37 males and three females, with ages ranging from 16 to 52 years. The patients were numbered randomly from 1 to 40: the even numbers underwent surgical correction using the ST-G tendons and the odd numbers, using the patellar tendon. Functional evaluations were made using the KSS and Lysholm scale, applied in the evening before the surgical procedure and six months after the operation. RESULTS: From the statistical analysis, it could be seen that the patients' functional capacity was significantly greater after the operation than before the operation. There was strong evidence that the two forms of therapy had similar results ( p= >0.05, in all the comparisons. CONCLUSIONS: The results from the ACL reconstructions were similar with regard to functional recovery of the knee and improvement of quality of life, independent of the type of graft. It was not possible to identify the best method of surgical treatment. The surgeon's clinical and technical experience and the patient are the factors that determine the choice of graft type for use in ACL surgery.

  18. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome.

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    Kenneth R Eyring

    Full Text Available Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM model of allergic airway disease, we measured airway hyperresponsiveness (AHR and airway inflammation between mice exposed prenatally to cigarette smoke (CS or filtered air (FA. DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3 are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease.

  19. Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects

    OpenAIRE

    Moreno-Vinasco, Liliana; Verbout, Norah G.; Fryer, Allison D.; Jacoby, David B.

    2009-01-01

    Inhibitory M2 muscarinic receptors on airway parasympathetic nerves normally limit acetylcholine release. Viral infections decrease M2 receptor function, increasing vagally mediated bronchoconstriction. Since retinoic acid deficiency causes M2 receptor dysfunction, we tested whether retinoic acid would prevent virus-induced airway hyperreactivity and prevent M2 receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperreactive to electrical stimulation of the vagus nerves,...

  20. Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2013-01-01

    Full Text Available Introduction: Primary hypothyroidism is one of the most frequent complications observed in-patients suffering from thalassemia. We investigated and reviewed the thyroid function in all thalassemic patients attending the Pediatric Endocrine Clinic of Hamad Medical Center, Doha, Qatar during the last 10 years of follow-up. Patients and Methods: A total of 48 patients with ί-thalassemia major between 5 years and 18 years of age. Thyroid dysfunction was defined as follows: Overt hypothyroidism (low Free thyroxine [FT4] and increased thyroid-stimulating hormone [TSH] levels >5 μIU/ml; subclinical hypothyroidism (normal FT4, TSH between 5 μIU/ml and 10 μIU/ml and central (secondary hypothyroidism (low FT4 and normal or decreased TSH. Results: A total of 48 patients (22 males and 26 females completed a 12 year-period of follow-up. During this period, hypothyroidism was diagnosed in 17/48 (35% of patients. There was no significant difference in the prevalence in males 7/22 (32% versus females 10/26 (38%. Sixteen of the patients had hypothyroidism after the age of 10 years (94%. The prevalence of overt hypothyroidism had risen from 0% at the age of 7 years to 35% at the age of 18 years. None of the patients had high anti-thyroperoxidase antibody titers. Out of 17 patients, 13 patients with hypothyroidism had normal or low TSH level (not appropriately elevated indicative of defective hypothalamic pituitary response to low FT4 (central hypothyroidism. Three patients (6.3% had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4. The general trend of FT4 level showed progressive decrease over the 12 years, whereas, TSH levels did not show a corresponding increase. These data suggested defective hypothalamic pituitary thyroid axis involving both TSH and FT4 sretion in patients with thalassemia major over time. There was a significant negative correlation between serum ferritin and FT4 (r = −0.39, P = 0.007, but no correlation

  1. Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years

    Science.gov (United States)

    Soliman, Ashraf T.; Al Yafei, Fawzia; Al-Naimi, Lolwa; Almarri, Noora; Sabt, Aml; Yassin, Mohamed; De Sanctis, Vincenzo

    2013-01-01

    Introduction: Primary hypothyroidism is one of the most frequent complications observed in-patients suffering from thalassemia. We investigated and reviewed the thyroid function in all thalassemic patients attending the Pediatric Endocrine Clinic of Hamad Medical Center, Doha, Qatar during the last 10 years of follow-up. Patients and Methods: A total of 48 patients with ί-thalassemia major between 5 years and 18 years of age. Thyroid dysfunction was defined as follows: Overt hypothyroidism (low Free thyroxine [FT4] and increased thyroid-stimulating hormone [TSH] levels >5 μIU/ml); subclinical hypothyroidism (normal FT4, TSH between 5 μIU/ml and 10 μIU/ml) and central (secondary) hypothyroidism (low FT4 and normal or decreased TSH). Results: A total of 48 patients (22 males and 26 females) completed a 12 year-period of follow-up. During this period, hypothyroidism was diagnosed in 17/48 (35%) of patients. There was no significant difference in the prevalence in males 7/22 (32%) versus females 10/26 (38%). Sixteen of the patients had hypothyroidism after the age of 10 years (94%). The prevalence of overt hypothyroidism had risen from 0% at the age of 7 years to 35% at the age of 18 years. None of the patients had high anti-thyroperoxidase antibody titers. Out of 17 patients, 13 patients with hypothyroidism had normal or low TSH level (not appropriately elevated) indicative of defective hypothalamic pituitary response to low FT4 (central hypothyroidism). Three patients (6.3%) had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4). The general trend of FT4 level showed progressive decrease over the 12 years, whereas, TSH levels did not show a corresponding increase. These data suggested defective hypothalamic pituitary thyroid axis involving both TSH and FT4 sretion in patients with thalassemia major over time. There was a significant negative correlation between serum ferritin and FT4 (r = −0.39, P = 0.007), but no correlation was

  2. The subtle body: an interoceptive map of central nervous system function and meditative mind-brain-body integration.

    Science.gov (United States)

    Loizzo, Joseph J

    2016-06-01

    Meditation research has begun to clarify the brain effects and mechanisms of contemplative practices while generating a range of typologies and explanatory models to guide further study. This comparative review explores a neglected area relevant to current research: the validity of a traditional central nervous system (CNS) model that coevolved with the practices most studied today and that provides the first comprehensive neural-based typology and mechanistic framework of contemplative practices. The subtle body model, popularly known as the chakra system from Indian yoga, was and is used as a map of CNS function in traditional Indian and Tibetan medicine, neuropsychiatry, and neuropsychology. The study presented here, based on the Nalanda tradition, shows that the subtle body model can be cross-referenced with modern CNS maps and challenges modern brain maps with its embodied network model of CNS function. It also challenges meditation research by: (1) presenting a more rigorous, neural-based typology of contemplative practices; (2) offering a more refined and complete network model of the mechanisms of contemplative practices; and (3) serving as an embodied, interoceptive neurofeedback aid that is more user friendly and complete than current teaching aids for clinical and practical applications of contemplative practice.

  3. Spruce Needle Polyprenols Protect Against Atorvastatin-Induced Muscle Weakness and do not Influence Central Nervous System Functions in Rats

    Directory of Open Access Journals (Sweden)

    Jansone Baiba

    2016-02-01

    Full Text Available Polyprenols (PPs have been identified in almost all living organisms. The richest source of PPs is the needles of conifer trees. Endogenously, PPs, similarly to cholesterol, are synthesised in human and animal cells via the mevalonate pathway. Previous studies have demonstrated the anti-oxidant properties of PPs. To our knowledge, no studies have been published on the influence of PPs on muscle strength. We hypothesised that administration of PPs could prevent changes in muscle functioning caused by statins (weakness, etc.. In the present study, atorvastatin (80 mg/kg was used as a model compound. PPs at doses 1, 10 and 20 mg/kg were administered. Both drugs were given per os for 16 days. The influence of atorvastatin, PPs and their combination on behaviour, muscle strength, plasma cholesterol and creatine kinase activity was assessed in female Wistar rats. Our data demonstrated that atorvastatin considerably impaired muscle strength, whereas PPs protected that effect. Neither PPs, nor atorvastatin influenced plasma cholesterol levels, whereas PPs at dose 20 mg/kg elevated creatine kinase activity by about 25%. PPs at the tested doses did not alter behaviour, indicating safety of central nervous system functions. The obtained data suggest usefulness of PPs as a complement in statin therapy to reduce muscle-related side effects.

  4. Targeted therapy of bronchitis in obstructive airway diseases.

    Science.gov (United States)

    Dasgupta, Angira; Neighbour, Helen; Nair, Parameswaran

    2013-12-01

    Guidelines for the management of obstructive airway diseases do not emphasize the measurement of bronchitis to indicate appropriate treatments or monitor response to treatment. Bronchitis is the central component of airway diseases and contributes to symptoms, physiological and structural abnormalities. It can be measured directly and reliably by quantitative assay of spontaneous or induced sputum. The measurement is reproducible, valid, and responsive to treatment and to changes in disease status. Bronchitis may be eosinophilic, neutrophilic, mixed, or paucigranulocytic (eosinophils and neutrophils not elevated). Eosinophilic bronchitis is usually a Th2 driven process and therefore a sputum eosinophilia of greater than 3% usually indicates a response to treatment with corticosteroids or novel therapies directed against Th2 cytokines such as IL-4, IL-5 and IL-13. Neutrophilic bronchitis which is a non-Th2 driven disease is generally a predictor of response to antibiotics and may be a predictor to therapies targeted at pathways that lead to neutrophil recruitment such as IL-8 (eg anti-CXCR2), IL-17 (eg anti-IL17) etc. Paucigranulocytic disease may not warrant anti-inflammatory therapy. Several novel monoclonals and small molecule antagonists have been evaluated in clinical trials with variable results and several more are likely to be discovered in the near future. The success of these agents will depend on appropriate patient selection by accurate phenotyping or characterization of bronchitis.

  5. Preparation of the patient and the airway for awake intubation

    Directory of Open Access Journals (Sweden)

    Venkateswaran Ramkumar

    2011-01-01

    Full Text Available Awake intubation is usually performed electively in the presence of a difficult airway. A detailed airway examination is time-consuming and often not feasible in an emergency. A simple 1-2-3 rule for airway examination allows one to identify potential airway difficulty within a minute. A more detailed airway examination can give a better idea about the exact nature of difficulty and the course of action to be taken to overcome it. When faced with an anticipated difficult airway, the anaesthesiologist needs to consider securing the airway in an awake state without the use of anaesthetic agents or muscle relaxants. As this can be highly discomforting to the patient, time and effort must be spent to prepare such patients both psychologically and pharmacologically for awake intubation. Psychological preparation is best initiated by an anaesthesiologist who explains the procedure in simple language. Sedative medications can be titrated to achieve patient comfort without compromising airway patency. Additional pharmacological preparation includes anaesthetising the airway through topical application of local anaesthetics and appropriate nerve blocks. When faced with a difficult airway, one should call for the difficult airway cart as well as for help from colleagues who have interest and expertise in airway management. Preoxygenation and monitoring during awake intubation is important. Anxious patients with a difficult airway may need to be intubated under general anaesthesia without muscle relaxants. Proper psychological and pharmacological preparation of the patient by an empathetic anaesthesiologist can go a long way in making awake intubation acceptable for all concerned.

  6. Effects of nebulized ketamine on allergen-induced airway hyperresponsiveness and inflammation in actively sensitized Brown-Norway rats

    Directory of Open Access Journals (Sweden)

    Qian Yan

    2007-05-01

    Full Text Available Abstract Since airway hyperresponsiveness (AHR and allergic inflammatory changes are regarded as the primary manifestations of asthma, the main goals of asthma treatment are to decrease inflammation and maximize bronchodilation. These goals can be achieved with aerosol therapy. Intravenous administration of the anesthetic, ketamine, has been shown to trigger bronchial smooth muscle relaxation. Furthermore, increasing evidence suggests that the anti-inflammatory properties of ketamine may protect against lung injury. However, ketamine inhalation might yield the same or better results at higher airway and lower ketamine plasma concentrations for the treatment of asthma. Here, we studied the effect of ketamine inhalation on bronchial hyperresponsiveness and airway inflammation in a Brown-Norway rat model of ovalbumin(OVA-induced allergic asthma. Animals were actively sensitized by subcutaneous injection of OVA and challenged by repeated intermittent (thrice weekly exposure to aerosolized OVA for two weeks. Before challenge, the sensitizened rats received inhalation of aerosol of phosphate-buffered saline (PBS or aerosol of ketamine or injection of ketamine respectivity. Airway reactivity to acetylcholine (Ach was measured in vivo, and various inflammatory markers, including Th2 cytokines in bronchoalveolar lavage fluid (BALF, as well as induciable nitric oxide synthase (iNOS and nitric oxide (NO in lungs were examined. Our results revealed that delivery of aerosolized ketamine using an ultrasonic nebulizer markedly suppressed allergen-mediated airway hyperreactivity, airway inflammation and airway inflammatory cell infiltration into the BALF, and significantly decreased the levels of interleukin-4 (IL-4 in the BALF and expression of iNOS and the concentration of NO in the inflamed airways from OVA-treated rats. These findings collectively indicate that nebulized ketamine attenuated many of the central components of inflammatory changes and AHR in

  7. Emergency surgical airway management in Denmark

    DEFF Research Database (Denmark)

    Rosenstock, C V; Kehlet Nørskov, Anders; Wetterslev, J;

    2016-01-01

    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...... 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...... per thousand (95% CI; 1.0-2.4). A Supraglottic Airway Device and/or the administration of a neuromuscular blocking agent before ESA were used as a rescue in 6/27 and 13/27 of the patients, respectively. In 19/27 patients ENT surgeons performed the ESA's and anaesthetists attempted 6/27 of the ESAs...

  8. Acoustic simulation of a patient's obstructed airway.

    Science.gov (United States)

    van der Velden, W C P; van Zuijlen, A H; de Jong, A T; Lynch, C T; Hoeve, L J; Bijl, H

    2016-01-01

    This research focuses on the numerical simulation of stridor; a high pitched, abnormal noise, resulting from turbulent airflow and vibrating tissue through a partially obstructed airway. Characteristics of stridor noise are used by medical doctors as indication for location and size of the obstruction. The relation between type of stridor and the various diseases associated with airway obstruction is unclear; therefore, simply listening to stridor is an unreliable diagnostic tool. The overall aim of the study is to better understand the relationship between characteristics of stridor noise and localization and size of the obstruction. Acoustic analysis of stridor may then in future simplify the diagnostic process, and reduce the need for more invasive procedures such as laryngoscopy under general anesthesia. In this paper, the feasibility of a coupled flow, acoustic and structural model is investigated to predict the noise generated by the obstruction as well as the propagation of the noise through the airways, taking into account a one-way coupled fluid, structure, and acoustic interaction components. The flow and acoustic solver are validated on a diaphragm and a simplified airway model. A realistic airway model of a patient suffering from a subglottic stenosis, derived from a real computed tomography scan, is further analyzed. Near the mouth, the broadband noise levels at higher frequencies increased with approximately 15-20 dB comparing the stridorous model with the healthy model, indicating stridorous sound.

  9. Silibinin attenuates allergic airway inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: ghyan@ybu.edu.cn [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  10. Macrophage adaptation in airway inflammatory resolution

    Directory of Open Access Journals (Sweden)

    Manminder Kaur

    2015-09-01

    Full Text Available Bacterial and viral infections (exacerbations are particularly problematic in those with underlying respiratory disease, including post-viral infection, asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. Patients experiencing exacerbations tend to be at the more severe end of the disease spectrum and are often difficult to treat. Most of the unmet medical need remains in this patient group. Airway macrophages are one of the first cell populations to encounter airborne pathogens and, in health, exist in a state of reduced responsiveness due to interactions with the respiratory epithelium and specific factors found in the airway lumen. Granulocyte–macrophage colony-stimulating factor, interleukin-10, transforming growth factor-β, surfactant proteins and signalling via the CD200 receptor, for example, all raise the threshold above which airway macrophages can be activated. We highlight that following severe respiratory inflammation, the airspace microenvironment does not automatically re-set to baseline and may leave airway macrophages more restrained than they were at the outset. This excessive restraint is mediated in part by the clearance of apoptotic cells and components of extracellular matrix. This implies that one strategy to combat respiratory exacerbations would be to retune airway macrophage responsiveness to allow earlier bacterial recognition.

  11. A Study of the Central Auditory Function in Stutters by Masking Level Difference and Synthetic Sentence Identification Tests

    Directory of Open Access Journals (Sweden)

    Afsaneh Rajab

    2007-06-01

    Full Text Available Background and Aim: There are evidences that indicate a relationship between auditory processing disor¬ders and stuttering,¬ and any disorder in the central auditory function can be at least one of the underly¬ing causes of stuttering. Even though, using the most state of the art radiographic technologies, i.e. MRI, no definitive answer has been given in relative to this question. In this research, using Mask-ing Level Difference (MLD and Synthetic Sentence Identification (SSI tests, the central auditory func¬tion of stutters and normal group was evaluated.Materials and Methods: In this study was analytic cross-sectional, fifteen male patients with stutter-ing and 15 male normal cases with the age range from 16 to 40 years (average age 26.78 year were evalu¬ated. SSI-ICM, SSI-CCM and MLD tests were performed. The results were compared in both groups.Results: Although stutterers mean MLD was less than that of normal group, the different was not signifi¬cant between stutters and normal group in SSI test in right ear at negative MCRs. There was a signifi¬cant difference in ICM state, but in CCM state, there was no significant difference between the aver¬age score of two groups in various MCRs.Conclusion: The findings of this research is compatible with those of similar researches about the SSI test and the pattern of results, probably indicates a partial dysfunction of brainstem in some of the stutters.

  12. Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only.

    Science.gov (United States)

    Hartwig, Isabel R V; Bruenahl, Christian A; Ramisch, Katherina; Keil, Thomas; Inman, Mark; Arck, Petra C; Pincus, Maike

    2014-10-01

    Observational as well as experimental studies support that prenatal challenges seemed to be associated with an increased risk for allergic airway diseases in the offspring. However, insights into biomarkers involved in mediating this risk are largely elusive. We here aimed to test the association between endogenous and exogenous factors documented in pregnant women, including psychosocial, endocrine, and life style parameters, and the risk for allergic airway diseases in the children later in life. We further pursued to functionally test identified factors in a mouse model of an allergic airway response. In a prospectively designed pregnancy cohort (n = 409 families), women were recruited between the 4th and 12th week of pregnancy. To investigate an association between exposures during pregnancy and the incidence of allergic airway disease in children between 3 and 5 years of age, multiple logistic regression analyses were applied. Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In addition to the prenatal stress challenge, some pregnant females were treated with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we observed that high levels of maternal progesterone in early human pregnancies were associated with a decreased risk for an allergic airway disease (asthma or allergic rhinitis) in daughters (adjusted OR 0.92; 95% confidence interval [CI] 0.84 to 1.00) but not sons (aOR 1.02, 95% CI 0.94-1.10). In mice, prenatal DHD supplementation of stress-challenged dams attenuated prenatal stress-induced airway hyperresponsiveness exclusively in female offspring. Reduced levels of maternal progesterone during pregnancy-which can result from high stress perception-increase the risk for allergic airway diseases in females but not in males. Key messages: Lower maternal progesterone during pregnancy increases the risk for allergic airway disease

  13. Recuperação espontanea da função nas lesões do sistema nervoso central Spontaneous recuperation of function in central nervous system lesions

    Directory of Open Access Journals (Sweden)

    Abrão Anghinah

    1975-12-01

    Full Text Available É feita uma revisão dos mecanismos apontados como responsáveis pela recuperação espontânea da função em pacientes com lesões do sistema nervoso central. São referidas as teorias de reorganização espontânea do tecido nervoso e da função vicariante. É destacada a contribuição experimental das duas últimas décadas, particularmente a dos pesquisadores encabeçados por Windle & Guth, que demonstraram a possibilidade de regeneração no sistema nervoso central, bem como as de Lawrence & Kuypers, Brodal & Goldberger, que advogam a função vicariante como mecanismo provável da recuperação da função.A rewiev of the mechanims responsible for the spontaneous recuperation of function in patients with lesions of the central nervous sistem is made. The spontaneous reorganization theories of the nervous structures and the vicarious function are also referred to. In the last two decades experimental contributions have been accentuated, specially the one conducted by the group of researchers directed by Windle and Guth, who had shown the possibility of regeneration in the central nervous system, as well Lawrende and Kuypers, Brodal, Goldberger and others, which defended the vicarious function as the probable mechanisms of recuperation.

  14. Central sensibility of human cases with different body mass during oral glucose tolerance test using functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Because of the limitation of technique, there are few researches on regulating function of